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306 Cards in this Set
- Front
- Back
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Receptor potential
vs synaptic potential vs action potential |
Receptor: due to activation of a sensory neuron from external stimuli
Synaptic: due to one neuron's synapse contacting another neuron's processes Action: unlike the two above, APs are not graded. They are all or none This is the "boost system" that allows for travel over the long distances in an axon without diminishing the signal. -Depolarization must be greater than a threshold in order for an AP to occur -Greater signals are made with more frequent APs, not with bigger depolarizations. |
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Electrical potentials across membranes are generated because...
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-There are differences in concentrations of ions across the membrane
and -membranes are selectively permeable to to some of these ions |
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2 types of membrane proteins that establish an electrochem gradient
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-active transporters-move ions actively against gradient
-ion channels-move passively with gradient |
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# of human genes for Na+ channels?
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10
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# of human genes for K+ channels and some example types?
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~100 types
examples: -delayed rectifier K+ are involved in APS -V4.1 inactive during a depolarization -HERG inactivated so quickly that a current is only seen at the very end of the depolarization, when inactivation is already removed -Inward rectifier allows more K+ to flow in when the cell is hyperpolarized, more so than when it is depolarized -Ca++ activated have larger currents with higher Ca++ concentrations -2-Pore- usually respond to chem signals, not membrane potential |
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which are more specific, ligand gated or voltage gated ion channels?
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V gated usually only let one ion in, while L-gated are usually less selective allowing in 2 or more ion types.
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examples of ligands for ion channels
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-Ca++ activates some K+ channels
-cAMP, cGMP activates K+/Na+ channels -glutamate (extracellular) can activate K+/Na+ channels --> these signals are later converted to electric ones |
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types of ion channels
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voltage gated
ligand gated stretch/heat activated (ex. auditory hair cells are mechanically activated) |
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Na+ and Ca++ channel structure
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-4 successive repeats of a 6 membrane spanning regions to make a total of 24 tm regions
-beta subunits, nearby peripheral or tm proteins, help to regulate function of the channels -only one unit of these 24 tm region protein is necessary for function as a channel |
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K+ channel structure
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-usually span membrane 6 times, but some that span 2,4 and 7 times are also known
-it takes 4 of these protein subunits to make 1 functional channel |
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ion selectivity in ion channels
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-2 ms regions form a pore for the ion to go through
-one of these regions contains a loops that confers selectivity |
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voltage sensor structure
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-usually one tm helix will be the voltage sensor per tm region.
-usually has many +charged aa's that face one side. |
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to block K+ channels:
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use TEA, tetraethylammonium or Cs+
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to block Na+ channels, use...
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TXX, tetrodotoxin
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Voltage Sensor position is important b/c...
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the positively charged voltage sensor allows for gating to be charge dependent. Depolarization causes the voltage sensor to move, creating conformational change that allows for conduction of ions.
-in K+ channels, sensor is on the inside when closed(hyperpolarized) and outside when depolarized(open) |
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How does the selectivity filter for a K+ channel work?
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there is an opening on the intracellular side that contains a vestibule and a bottleneck, where K+ ions are dehydrated. K-O bonds are replaced by 4 carbonyls in the filter. Since Na+ ions are too small to interact with all 4, they would rather stay hydrated and not enter the bottleneck.
-this filter was originally discovered in bacterial cells, but is conserved in mammalian cells. -the pore attracts ions toward the filter with 2 neg. charged alpha helices |
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speed of ion channels vs transporters
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channels: thousands of ions per millisecond
transporters: require ion binding, a conformational change and unbinding, taking several milliseconds for one transfer |
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two types of transporters based on what energy they use
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ATPase pumps use the energy of ATP hydrolysis
-ex. Na+/K+ pump creates the membrane potential -ex. Ca++ pump removes Ca++ from inside the cell Ion Exchangers- cotransport one ion with it's gradient and one against it. -usually use Na+ as the energy confering transfer -ex. Ca++/Na+ to keep Ca++ out -ex. H+/Na+ to maintain cellular pH -since these use Na+ transport, they too ultimately depend on ATPase Pumps. |
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Properties of the Na+/K+ pump
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-uses 20-40% of brain's energy
-is electrogenic in that it creates an electrical current by transporting 3 positive charges out, but only 2 in. -in most circumstances, this pump does not contribute to the membrane potential significantly |
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differences and similarities b/w K+ channels
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same voltage to conductance profiles, but different inactivation properties
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K V2.1 channel properties
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-very similar to K+ channels that cause APs
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K V4.1 channel Properties
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-inactivate like Na+ channels after opening
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K+ Inward rectifier channel properties
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- cause an outward flux when the cell is hyperpolarized
-only type of K+ channel that creates an inward (not outward) current -activated by depolarization, not hyperpolarization |
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Ca++ activated or
2-pore pH activated |
the number to channels that open are based on Ca++ or H+ concentrations
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Use of xenopus oocytes in channel research
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oocytes contain a great deal of protein synthesis machinary
-isolate DNA for channel gene (possibly mutate to compare) -can inject mRNA for it into oocyte -study expressed protein with whole cell recording or just study one channel with patch clamping techniques |
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Can get through a Na+ channel
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Na+
Hydrazine Hydroxylamine Li+ BUT not K+ |
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differnces between the bacterial and mammalian K+ channel
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-bacterial is not voltage gated (no sensors)
-bacterial only has 2 tm helices per subunit -human also has a T1 domain in between the tm regions and the beta subunit regions |
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How many types of neurotransmitters?
What are the 2 classes? |
>100 neurotransmitters
2 main catergories: neuropeptides (much larger, 3-36 aa's long) and small molecule neurotransmitters, which includes the biogenic amines class |
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small molecules neurotransmitters
4 subclasses |
Acetylcholine
Amino acids Purines-ATP Biogenic Amines-catecholamines, indoleamines and imidalozeamines |
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Neurotransmitter Amino Acids
4 transmitters |
-Glutamate
-Aspartate -GABA -Glycine |
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Neurotransmitter Biogenic Amines
5 transmitters in 3 classes |
Catecholamines(Benzene w/ hydroxyls)
-Dopamine -Norepinephrine -Epinephrine Indolamines(Benzene with hydroxyl and an amine ring) -Seratonin Imidazoleamine (just N ring) -histamine |
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How is ACh made?
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Acetyl CoA (from Pyruvate) + Choline (from outside the cell) are joined by Choline acetyl transferase (CAT) to make Acetylcholine
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Where is ACh synthesized?
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-glucose bcms Pyruvate in cytoplasm
-Mitochondria make Pyruvate into Acetyl CoA -Choline enters the cell by a na+/choline pump -these two are joined inside the presynaptic terminal |
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How are small molecule neurotransmitters made in comparison to neuropeptides?
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sm. transmitters use raw materials brought into the presynaptic terminal by active transport. They make and package transmitters locally.
vs. n.peps are synthesized in the cell body like other proteins and loaded into vesicles to be transported along microtubules in the axon. |
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How are neuropeptides made?
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prepropeptides are made in the cell body and sent to the ER where their signal sequence is cleaved to make a propeptide.
the propeptide is then cleaved into a few functional peptides |
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Where is ACh used?
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-in skeletal neuromuscular junctions
- in the neuromuscular junction between the vagus nerve and cardiac muscle -in the visceral motor system -in the CNS |
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How do you get rid of ACh after release?
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-not uptake like most sm. transmitters
-a hydrolytic enzyme, acetylcholine esterase (AChE), removes it from the synapse -AChE has high catalytic activity:5000 molecules/s |
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What does AChE do?
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Acetylcholine esterase
-an enzyme that cleaves ACh into acetate and choline after it is released into the synaptic cleft. |
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AChE inhibitors
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Sarin and Soman, both nerve gases, cause a buildup of ACh and overstimulation of cholinergic synapses.
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What does Glutamate do?
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Most imp. transmitter for normal brain fxn
-nearly all excitatory neurons in the CNS are glutamatergic -too much can kill the post-synaptic neuron by excitotoxicity (strokes) |
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How is Glutamate Made and taken back up?
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-made from Glutamine by Glutaminase
-taken back up by neurons or glia -glia take it up, convert it back to Glutamine by Glutamine Synthase and spit it back out |
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GABA and Glycine function and reuptake?
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-Inhibitory transmitters
-inhibit APs from firing -both rapidly taken back up by glia and neurons |
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Synthesis of GABA
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-made from Glutamate by Glutamic Acid Decarboxylase (GAD) and requires Vitamin B6 as a cofactor
-remember that Glutamate is first made from Glutamine |
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Vitamin B6 Deficiency is a problem because..?
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it is a cofactor for GABA synthesis
-deficiency can lead to loss of synaptic transmission |
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What is Hyperglycemia?
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a form of mental retardation caused by a defect in glycine uptake and removal
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How does Glycine work and where is it found?
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-1/2 of spinal cord neurons use it (ventral sprinal cord mostly)
-makes postsyn membrane more permeable to Cl-, hyperpolarizing the cell and inhibiting APs |
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What is Strychnine?
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blocks binding of glycine
-binds without opening Cl- channels -therefore inhibits inhibition and causes spinal hyperexcitability |
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what is the precursor of catecholamines?
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Tyrosine
-Tyrosine hydroxylase catalyzes the rate limiting step and is a good marker of catecholaminergic neurons. |
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How and where is dopamine made?
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a catecholamine: made from tyrosine and uses tyrosine hydroxylase (to make DOPA) and the enzyme DOPA decarboxylase to make dopamine
-made by substantia nigra and mostly found in the corpus striatum (essential for coordination of body movements) |
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What does Dopamine do?
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-dopamine plays a key role in coordination and motor function
-also involved in reward, motivation, reinforcement |
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what drugs and diseases are associated with dopamine's function?
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-dopamine plays a key role in coordination and motor function
- In Parkinson's, dopaminergic neurons in the substantia nigra degenerate -treatment includes Leva-DOPA (crosses bb barrier) and degradation enzyme inhibitors -cocaine inhibits uptake of dopamine so that dopamine receptors are all occupied |
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1)tyrosine ---> DOPA is catalyzed by...?
2)DOPA---->Dopamine is catalyzed by? 3)Dopamine---> Norepinephrine 4)Norepinephrine--> Epinephrine |
1)tyrosine hydroxylase
2) DOPA decarboxylase 3)Dopamine B-hydroxylase 4)Phenylmethanolamine N-transferase |
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norepinephrine uses
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-sympathetic ganglion cells use it on the visceral motor system for fight or flight
-the locus coeruleus in the brainstem projects it to other areas to control attention, feeding, sleeping |
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norepinephrine synthesis and reuptake
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-Dopamine-->norepinephrine by dopamine-beta-hydroxylase
-taken back up by the norepinephrine transporter (NET) -NET is the target of many amphetamines |
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epinephrine: what does it do, where does it function?
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Adrenaline
-is present in lower levels than other transmitters -made by the rostro medulla, and project to the thalamus and hypothalamus |
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Serotonin
made how? from where to where? |
aka 5-Hydroxy Tryptamine (5HT)
-made from tryptophan -Found primarily in the raphe region of the pons and upper brainstem -project to forebrain areas involved in sleep and wakefulness |
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Serotonin:
reuptake and drugs |
-reuptake by serotonin transporters
-SSRI drugs like prozac act by inhibiting reuptake |
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Histamine
-made from? -metabolized by? |
-made by histidine
-metabolized by monoamine oxidase- |
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Histamine
-made where? -projects where? -function? |
-made by hypothalamus and projects to neurons in all of CNS
-immune system has receptors for Histamines too -mediates arousal and attention -this is why antihistamine benedryll makes you drowsy |
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ATP and other purines
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-general excitatory
-contained in all synaptic vesicles -in spinal cord, motor neurons and other ganglia |
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large dense core vesicles vs. small clear core vesicles
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-neuropeptides are kept in large dense core vesicles while small transmitters are kept in small clear core vesicles.
-clear core release upon a single AP and are stored closer to the membrane -Large core vesicles take more effort and need multiple APs |
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what protein is key for electrical transmission in a gap junction?
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connexin protein makes up pores that directly connect 2 neurons and allow for charge(via ions) to diffuse bidirectionally between them.
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describe the synapses at neuromuscular junctions
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simple, large and peripherally located
-between spinal motor neuron and skeletal muscle -synapses form flat structures called end plates that lay over part of a muscle fiber |
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EPPs
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end plate potentials
-generated at the end plate and only the end plate. You cannot detect them from the connecting muscle fiber. -can be seen as a bump at the base of an end-plate AP -made by summing a lot of MEPPs ~50mV |
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MEPPs
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~1mV
-can occur spontaneously, even w/o an AP -sensitive to agents that block Ca++ or ACh -one MEPP=1 vesicle of ACh |
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Quantal Neurotransmission
Bernard Katz |
the MEPP is a quantal event of neurotransmission
-one MEPP in the postsynaptic cell indicates that the presynaptic cell released one vesicle (~10,000 molecules) -not continuous because ACh comes in packets. |
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pulse chase experiment
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showed the exocytosis and endocytosis cycle by which vesicles are locally recycled
-visualized with Horseradish peroxidase (HRP) the cycle goes:(in 1 min) -endosome -budding out w/ clathrin -docking -priming (+ca++) -fusion -budding in w/ clathrin -endosome again |
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ways to show that vesicle fusion and neurotransmission is calcium dependent
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-can see inward flux in presynaptic cells with voltage gating
-injection of calcium into a presyn neuron will cause a potential in the postsyn neuron -chelating calcium, or removing extracellular calcium, or blocking channels with cadmium will inhibit a potential in the postsyn neuron |
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synaptotbrevin
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-the v snare(vesicle snare) involved in vesicle fusion
-located next to synaptotagmin |
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Snap 25
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snap-25- regulates the assembly of synaptobrevin(on vesicle) and syntaxin(on plasma membrane)
-snap 25, syntaxin and synaptobrevin all wind around one another and pull the vesicle into the plasma membrane when synaptotagmin senses that calcium ions are nearby |
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medulla
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closest to spinal cord
regulates respiration and blood pressure |
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pons-ventral and dorsal regions
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VENTRAL region has pontine nuclei that relay information from the cortex to the cerebellum (air vents in a pontiac)
DORSAL regulates taste, sleep and respiration |
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brainstem
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-medulla, pons, midbrain
-target or source of all cranial nerves( head and neck) -also a throughway that must be passed by any signals going up or down -all you need to live chicken |
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cerebral hemispheres
contains what 4 important substructures? |
-largest portion of the brain
contains: cortex (cognitive fxn) basal ganglia(control of fine movement) Amygdala (social behavior and expressing emotions) Hippocampus(memory) |
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How is the cerebellum organized?
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-neurons in sheets (cortexes)
-two hemispheres with several lobes divided by fissures -contains a purkinje cell layer on the outside and a deep white matter layer on the inside |
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function of the cerebellum
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-used for motor control, particularly fine movement and posture
-essential for coordination of movements, planning them, learning them and storing this information. -also used for higher cognitive function, like language. |
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Where does the cerebellum receive it's input from?
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-spinal cord
-cerebral cortex -inner ear and vestibular organs for balance |
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Components of the Diencephalon
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Thalamus
-sensory switchboard to the cortex -essential for getting peripheral sensory info to the cortex, and sometimes filtering it Hypothalamus -ventral to the thalamus and connected to all parts of the brain -imp for pituitary gland regulation, maternal behavior, eating, drinking growth -also imp. for initiating and maintaining rewarding behaviors |
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Thalamus
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-pair of oviod structures
-sensory switchboard -connections to the cortex are highly organized(into nuclei) and mostly reciprocal |
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Cerebral Cortex
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2 major parts:
Cortex and subcortex -seat of cognition -does not work alone |
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cerebral cortex
-organization and structure |
Highly convoluted with grooves (sulci, or fissures if very deep) and bumps (gyri)
-2-4 mm thick, holding ~100,000 neurons per square mm -seperated into left and right hemispheres that connect at the corpus callosum -4 lobes -organized into layers -gray matter |
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cerebral subcortex
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-white matter
-subcortical nuclei -empty venticles in the middle -corpus callosum and anterior commisures are in the middle of white matter (centermost) b/w hemispheres |
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cerebral subcortex:
3 classes of white matter pathways |
ascending
descending cortico-cortical |
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cortico-cortical pathways
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pathways within the cortex
-between hemispheres: commisures and corpus callosum -lengthwise along a hemisphere short and long(fisciculi) |
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ventricles
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a system of interconnected fluid filled cavitites in the center of the brain
-contain CSF, cerebral spinal fluid |
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lobar anatomy of the cerebrum
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-frontal lobe
-central sulcus -parietal lobe -parieto-occipital sulcus -occipital lobe -preoccipital notch -temporal lobe |
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primary vs. non primary cortex
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primary- the primary projection fields targeted by sensory info and principal fields that have neurons to project back into the spinal cord
non-primary-everything in between (like interneurons) . Refered to as the association cortex |
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primary visual cortex?
primary auditory? primary somato? primary motor? v.a.s.m. |
vasm= cal hesch post pre
visual=calcarine sulcus(occipital) auditory=heschl's (temporal lobe) somato=post-central gyrus (parietal) motor=pre-central gyrus(frontal lobe) |
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How many layers are there in the cerebral cortex?
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6 can be seen by staining cell bodies
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Lissencephaly
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"smooth brain" phenotype
-do not see characteristic gyri patterns -due to defects during neural migration in development |
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nerves spanning from the spinal cord?
4 sections |
from the bottom to the brain:
sarah likes terry-cloth sacral, lumbar, thoractic, cervical -the spinal cord goes to the first lumbar vertebra -regions that innervate limbs are thicker (cervical and lumbar) |
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frontal lobe fxn
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planning responses to stimuli
contains motor cortex (precentral gyrus) |
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Parietal lobe fxn
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somatic sensory cortex
-post central gyrus somatic= voluntary movement |
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Temporal Lobe
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-under parietal and frontal, in front of occupital
home to the auditory primary cortex (heschl's) -involved in speech, memory, hearing -contains hippocampus -contains insular cortex (taste) |
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Occipital Lobe
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In the lower back region
-contains primary visual cortex (calcarine sulcus) |
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ventral vs. dorsal
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ventral-towards the stomach
dorsal-towards the back |
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Cortex dysfunctions
Reelin mutation DCX mutation |
Reelin-less complicated gyri pattern, smoothed out brain
DCX- double cortex mutation, X linked and only affects girls. creates 2 layers of gray matter Both are caused by developmental issues |
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Laminar Organization
what is the function of ... layer II and III? layer IV? layer V and VI? |
6 layers: superficial to deep
Can infer the function of a cortex region by seeing which layers are thick or thin II and III-corico-cortical output IV-primary input layer V and VI- descending output layers |
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Broca vs. Gull on cortical phrenology
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Gull-thought bumps show which cortex areas were most used and represented regionalized functions
Boca-thought the colvolutions mattered more, and that function was localized in the brain. |
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Broca's Aphasia
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understand, but can't speak properly
-caused by a stroke in Broca's area, in the frontal lobe (where motor function is controlled) |
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Wernicke's Aphasia
"receptive aphasia" |
Speaks fluently (not a motor issue) but has difficulty finding the correct words, bad comprehension
-This is caused by a stroke in Wernicke's area, located in the temporal lobe, home of the auditory cortex, responsible for processing hearing |
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Conduction Aphasia
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-inability to produce the right response, even though the communication is understood.
-difficulty repeating words -associated with damage in the Arcuate fasiculus, which connects Broca's and Wernicke's area |
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Arcuate Fisciculus
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major association fiber tract
-connects Broca's area to Wernicke's area -Damage to it causes conduction Aphasia |
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K+ concentrations
-intracellular -extracellular |
in: 140 mM
out: 5 mM |
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Na+ concentrations
-intracellular -extracellular |
in: 10 mM
out: 145 mM |
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Cl- concentrations
-intracellular -extracellular |
in: 30 mM
out: 110 mM |
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Ca++ concentrations
-intracellular -extracellular |
in: .0001 mM
out: 1 mM |
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how is ion permeability measured expirementally?
what is the equation for it? |
-membrane conductance is easier to work with (g)
g(ion)=I(ion)/(Vmemb-Eion) g= I/(Vm-E) |
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Golgi staining
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potassium chromate and silver nitrate
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The neuron doctrine
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proposed by Ramon y Cajal
-neurons are cells and each one is an individual entity -neurons have a functional polarity -challenged Golgi's reticular theory |
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glial cell properties and facts
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-outnumber neurons 10-50 fold
-critical in brain development -crucial role in synaptic formation -crucial for reuptake and support -microglia and macroglia macroglia: oligodendrocytes, astrocytes, shwann cells |
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Microglia
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-phagocytes
-like the macrophages of the nervous system --repair damage after injury |
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Astrocytes
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-most numerous glia
-have long, star shaped processes -type of macroglia -restricted to the CNS -maintain a proper chemical environment for signaling |
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Oligodendrocytes
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-myelinate cells in the CNS
-can myelinate multiple axons at once -a type of macroglia |
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Shwann cells
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-a type of macroglia
-myelinate neurons in the PNS -one cell can only myelinate one axon |
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Ependymal cells
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-a glial/epithelial cell that maintains the blood brain barrier
-important for surrounding the ventricals |
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Axonal Trasport
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-uses the neurofilaments, actin microfilaments, and microtubules in the axon
-Fast axonal transport moves neuropeptides and uses ATP -slow axonal transport moves vesicles of enzymes to make small molecule transmitters in the synapse |
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Types of neurons
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can be divided by morphology:
-uni, bi multipolar can be divided by function -sensory, motor and interneurons |
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Purkije Cells
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in the cerebellum
-have huge processes -massive webs of dendrites -makes up gray matter in the cerebellum's cortex |
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Cortical pyramidal cells
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-multipolar dendrites that contain both apical and basal denrites
-most common excitory neuron in the cerebral cortex |
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ganglion
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a collection of 100s-1000s of neurons outside of the CNS that are usually along nerves
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Properties of an AP
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-rapid
-transient -all of none -self regenerating -can go long distances -highly stereotyped -discrimination is based on patterns of firing |
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somatic vs. autonomic (visceral) motor system
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somatic-skeletal muscle
autonomic-smooth muscle, cardiac muscle, glands(effectors) |
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The Route of Olfaction
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1) odorants enter the nose and bind to specific receptors found in the olfactory epithelium
2)The olfactory epithelium projects ipsilaterally to neurons in the olfactory bulb 3)the olfactory buld projects neurons contra and ipsilaterally to the pyriform cortex in the temporal lobe and other forebrain structures |
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The pyriform cortex
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• Pyriform cortex is only 3-layered (sometimes called the
archicortex), and is considered older than the neocortex. • Unique among senses in that it does not include a thalamic relay between primary receptors and the cerebral cortex. • Pyriform cortex relays information via the thalamus (in the descending pathway) to the associational cortex to initiate motor, visceral, and emotional reactions to olfactory stimuli. |
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The Route of odorants to the Olfactory Bulb
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1)odorants bind to receptors (exposed to the air in the nasal epithelium)
2)Receptors send electrical signals through nasal nerve to glomeruli that are odor specific. 3)glomeruli in the bulb converge onto Mitral cells. 4)the olfactory tract forms a connection between the bulb and its targets (Pyriform cortex, Amygdala, entorhinal cortex, and Olfactory tubercle |
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Olfactory perception:
Why are humans worse at it than most other animals? |
-because other animals' greater number of different olfactory
receptors - the greater density of receptors, -the amount of cortex used to process information. -human = 12 million ORCs -typical dog= 1 billion ORCs |
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Asnosmics
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-people who cannot smell certain odorants
-can be congenital, or due to injury/ virus |
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The vomeronasal organ VNO
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-used for detecting species specific pheromones
-The VNO projects to the accessory olfactory bulb, which in turn projects to the hypothalamus/Amygdala - In animals, a lesion in the VNO severely compomises sexual reproduction, sexual selection and social heirarchies, unlike a lesion in the main olfactory projection |
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Olfactory Receptors
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• Discovered by Linda Buck and Richard Axel.
• They found that olfactory receptors comprise a large GPCR gene family. • Each olfactory neuron expresses a single olfactory receptor • Each receptor can bind to multiple odorants. • Each neuron that expresses a given receptor targets to the same glomeruli in the olfactory bulb. |
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Olfactory Receptor organization
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-There are zones in the nasal epithelium that remain separated in the olfactory bulb, and go to different glomeruli in it
-ORCs with the same receptors converge on the same glomeruli -a different set of odor receptors are expressed in each zone |
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5 basic tastes
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• Sweet (sucrose, aspartame, glycine, etc.)
• Sour (H+) • Salty (Na+, some other salts) • Unami (savory, glutamates) • Bitter (alkaloids) |
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VMO pathway
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The vomeronasal organs are distinct and project to the accessory olfactory bulb, which in turn projects to the hypothalamus (via amygdala-not in her notes)
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Olfactory Receptor signal transduction
How does binding cause depolarization? |
1) an airborne odorant binds a GPCR in the olfactory epithelium(each receptor can bind to one to a few molecules)
2)Binding activated the alpha subunit of G-olf to activate Adenylyl Cyclase 3)Adenylyl cyclase makes cAMP 4)cAMP gates a Na/Ca cation channel, allowing both to depolarize the cell. 5) Calcium rushes in and gates a Cl- channel. In ORC's, Cl- concentration is higher inside, so the the anions rush out, causing even more depolarization. This system ensures an AP will result. |
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How does adaptation occur in Olfactory receptor signal transducction?
(how does sensitivity to a stimuli decrease with time) |
-subsequent odorant molecules will not cause as much depolarization because:
-calmodulin will bind Ca++, preventing it from gating the Cl- channel -Cl- channels close -Ca++ will be pumped out |
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Pathways in the Olfactory Bulb
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-where the binding info is collected and sorted
-sensory neurons(many with one receptor type) project to a glomeruli -In glomeruli, they synapse onto Mitral cells -Mitral cells project to the cortex (mostly pyriform) |
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Neurons of the Olfactory bulb
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-ORCs synapse here
-Mitral cells: dendrites on a single glomerulus and the axon to brain -Tufted cell: contacts multiple glomeruli -Interneurons, horizontal periglomerular cells, also process(probably inhibition, like the horizontal cells of the retina) |
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neural stem cells
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-Olfactory system is in the adult CNS can regenerate neurons
-ORCs are easily damaged -stem cells in the epithelium (nearby) or the subventricular zone (SVZ) can be made and repopulate -SVZ stem-cell made ORCs must do chain migration to get to the olfactory epithelium |
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What other systems work with the Gustation pathway?
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-The GI system gets it ready to recieve food(saliva and swallowing) or to reject it (gagging or regurgitation)
-Information about texture and temperature of food is provided by the somatosensory system (trigeminal) |
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What three cranial nerves innervate the tongue?
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VII- taste buds in the anterior 2/3 of the tongue
IX-taste buds in the posterior 1/3 of the tongue X-taste buds in the epiglottis and top larynx *all three of these converge on the Nucleus of the the solitary tract(in the medulla) with VII axons at the top and X axons at the bottom |
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Gustation Pathway:
Tongue to brain |
1)taste cells, organized into taste buds tongue (three cranial nerves) synapse on the Nucleus of the Solitary tract (gustatory nucleus) in the Medulla
2)Slitary nucleur complex neurons synapse on the Ventral posteriomedial nucleus (VPMpc) in the Thalamus 3) Neurons of the VPM synapse on the gustatory cortex, at the lateral sulcus, extending a bit onto both the temporal and the frontal lobes. -The gustatory cortex is anterior to the postcentral gyrus -This information may go to Amygdala |
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Tastants and Taste Perception
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-most tastes are hydrophillic molecules solubilized in saliva
-Quantity of substance is percieved and translates to intensity of a taste -Tastants act in the millimolar range, except for bitter things (ex. strychnine, poisonous alkaloid .1microM) -Tongue is not strictly regionalized, but patterns exist. |
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What are the three types of papillae and where on the tongue are they found?
What are their proportions? |
-taste buds have 30-100 taste cells, and are mostly found in papillae (bumps on the tongue)
1)fungiform papillae(25%)-found on the anterior tongue (smallest) 2)Circumvallate papillae(50%)-found on rear of the tongue(largest) 3)Foliate Papillae(25%)-found on the posteriolateral edges(intermediate size) |
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Taste receptor signal transduction:
Salty or Sour |
-these are ions: Na+ or H+ that can open channels
-channel names:"Amiloride sensitive" Na+ channel or H+ TRP channel "PDK" -They depolarize the neuron and open voltage gated Na+ channels -This depolarization is greater and can open voltage gated Ca++ channels -Ca++ will cause transmitter release |
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Taste receptors:
What are the subunits for sweet or umami or bitter receptors |
-all use GPCRs: receptors, not channels
-Sweet: T1R3/T1R2 -Umami/amino acids: T1R3/T1R1 -Bitter: uses T1R2 only and the Gprotein has a specific name, Gustducin |
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Taste receptor signal transduction:
For GPCRs (sweet, umami, bitter) |
-the GPRC (T1R1/3 or T1R2/3 or T1R2 only) will activate the Gprotein
**this is all the same for the three** -The alpha subunit will activate phospholipase C-beta to make IP3 -IP3 will open ligand gated calcium channels "TRPM5" -calcium will depolarize and allow for vesicle fusion. |
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Excitation and Contraction Process
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1)AP in motor neuron axon
2)End Plate Potential (EPP) at the neromuscular junction 3)Action potential in muscle fiber 4)The AP in the muscle fiber is followed by a short latency and then a twitch in the fiber -This twitch is the all or none contraction (tension) |
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The three types of movement
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Reflex Responses
Rhythmic motor patterns Voluntary movements |
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Reflex Responses
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Rapid, stereotyped, involuntary movements
-knee jerk -withdrawl from pain -swallowing |
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Rhythmic Motor Patterns
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typically, the initiation and termination of the activity is voluntary
-walking -running -chewing |
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Voluntary Movements
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Are largely learned and goal oriented
and Improve with practice -playing the piano -writing |
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What 4 highly coordinated systems control movement?
|
-Lower Motor system
-Upper Motor system -Basal Ganglia -Cerebellum |
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Lower Motor System
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Gray matter of the spinal cord and brainstem
-contains lower motor neurons and lower circuit neurons -This is the final common path traveled by all motor output |
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upper Motor System
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-Sends info to the spinal cord
-Initiates all voluntary movement -contains the motor cortex(planning, initiating and directing movements) and some brainstem centers(basic movements and postural control) |
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Cerebellum
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-No direct access to lower motor system
-It must connect To upper motor systems as a bypass -Is responsible for motor learning -responsible for sensory motor coordination for ongoing movements |
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Basal Ganglia
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-Suppresses unwanted movement
-Primes neurons for the initiation of wanted movements -Parkinson's and Huntington's are diseases of the basal ganglia |
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Motor Neuron Organization
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-cell bodies of motor neurons are found in the ventral horn of the cord
-each motor neuron innervates muscle fibers within a single muscle -All motor neurons innervating a single muscle are clumped together in "motor pools" |
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Motor Pool organization
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-Motor pools are located near their targets with a slight spread along the Anterior-Posterior axis
-in the ventral horn, neurons that innervate axial, proximate musculature (the trunk) are located medially -Neurons that innervate the distal muscles(like hands) are located laterally in the ventral horn. |
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Types of Motor Neurons
-alpha vs. gamma |
Alpha Motor neurons
-innervate the extrafusal muscle fibers -these extrafusal muscle fibers generate the force needed for movement Gamma Motor neurons -innervate intrafusal muscle fibers (muscle spindles). muscle spindle fibers are also innervated with proprioception afferents |
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The motor unit
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-the smallest unit of muscle activity
-a motor neuron and the fibers it innervates -each fiber connects to only one alpha motor neuron, but each motor neuron connects to multiple fibers -an AP in the motor neuron is enough to bring all the fibers it is contacting to threshold (in order to contract) -one motor neuron axon separates into many synapses (end plates on fibers) with endplates synapsing on different fibers |
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Small motor neurons
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-make up "slow"(S) motor units
-Small motor neurons innervate relatively few muscle fibers and form motor units that generate small force -innervate "red" , smaller muscle fibers -red muscle contracts slowly, but is resistant to fatigue -red muscle contains a lot of mitochondria (ATP) and myoglobin -especially important for activities that require sustained, mild muscle contraction (like posture) |
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Large motor Neurons
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-form FFs, fast fatigable motor units
-innervate larger, more powerful units -innervate large pale muscle fibers with less mitochondria -generate more force, but easily fatigued |
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Skeletal Muscle Fiber types
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Type I-innervated by S pools, darkest (red)
Type IIb- FR intermediate in color and force Tpe IIa- FF are lightest |
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The Size principle
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-more stimulation leads to more contraction by muscle
-at low stimulation only S groups are on, but with an increase, FR, then FF will be recruited -AP frequency is also a factor. If the fiber has not fully relaxed from contraction when it is stimulated, it can generate more force.(ex. fused tetnus) -force to stimulation ratio is not linear because of summation of force |
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Spinal Cord circuits revisited
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-Ia afferents for spindles will synapse on motor or interneurons in the ventral horn
-inhibitory interneurons for antagonistic muscles -a negative feedback loop is used to maintain muscle length at a desired value (set by descending pathways) |
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Reaction to a passive stretch reflex
(the beercup ex.) |
1. spidle stretch from poured liquid weight activates a sensory neuron
2. sensory neuron synapses on ventral cord motor neurons and interneurons 3. the same and synergystic muscles' motor neuron activity is increased (contract) 4. Antagonistic muscles will have decreased motor activity because of inhibitory motor neurons 5. the muscle spindle length is maintained despite the stretch |
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Gamma Motor neurons
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-When the muscle is stretched, the spindle is stretched and spidle afferents will fire
-When the muscle is contracted, the afferents will not feel anything without gamma motors, which create tension on the spindle by contracting the intrafusal fibers -This maintains the tension at all times by wither alpha or gamma motor neurons and allows the spindles to continue functioning, even during contraction |
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Gain (Gamma bias)
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Spindles can adjust how much output will happen when they are stretched
-large gain means a small stretch of intrafusal fibers will cause a large increase in the number of active motor neurons and firing rates -Gain can be adjusted to meet circumstances |
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Golgi tendon organ
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-analogous to a spindle but is located at the junction of the muscle and the tendon
-each tendon is innervated by one Ib afferent that is mixed with collagen fibrils -Unlike spindle fibers, golgi tenson organs fire when the muscle contracts, not when it is stretched --Ib axons from Golgi tendon organs contact inhibitory local circuit neurons in the cord -These inhibitory interneurons synapse with alpha motors that innervate the same muscle -This inhibits the muscle to prevent fatigue: A negative feedback loop to contraction |
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Flexion Reflex pathways
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-Reflexes that compensate posture when one withdrawls from pain
-Not monosynaptic like knee jerk -excitation of a nociceptor leads to opposite in the ipsilateral side(withdraw by contracting flexor) and the contralateral side(straighten out leg by extensor) -the anatgonist will be inhibited |
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The Cross extension reflex (flexion pathway)
-to lift? -to stand? |
to lift: positive toflexor motors in the ipsilateral leg and negative to the extensor in the ipsilateral leg
to stand(contralateral leg) -positive to extensor -negative to flexor remember "exit out" the extensor is on the outside on the thigh |
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Locomotion by local cicuits
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-created by pattern generators that only need initiation and termination signals from upper motor pathways
-There is a stance phase (extensor) and a swing phase (flexor) -An increase in speed causes the stance phase to be shorter, but will not change the swing phase much |
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Step order with speed in quadreceps
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-the order of steps (limb pattern) changes with speed
walk: left side than right (in sequence) trot: Right forelimb and left hindlimb (and vise versa) will be synchronized run: two front limbs and two hind limbs are sunchronized |
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Upper motor control
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-upper axons influence local circuit neurons in the brainstem and spinal cord
-upper areas include brainstem centers(posture) and cortical areas (motor and premotor) in the frontal lobe( planning and control of voluntary movement sequences) |
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Spinal Cord Motor organization
-Gray matter |
-ventral gray matter
lateral local circuit neurons connect to lateral lower neurons in the medial intermediate area and medial horn (respectively) Lateral local circuit neurons in the lateral intermediate gray matter connect with lateral lower motor neurons in the ventral horn for distal muscle control. -long distance vs. short distance interneurons in the intermediate zone (local circuit neurons) |
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Spinal cord motor organization
-white matter |
descending upper motor axon tracts are located in the white matter
-axons from the motor cortex travel in lateral white matter in between dorsal and ventral horns on each side -axons from the brainstem travel in the medial white matter in between the ventral horns of each side -brainstem info (posture) travels to both sides -cortex info travels to only contralateral side(skilled movement) |
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Brainstem Centers of Upper Motor Neurons
-vestibular nuclei |
vestibular nuclei- receive info from the inner ear and project to medial regions of the spinal gray matter
-control axial/proximal -called the vestibulospinal tract |
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Brainstem Centers of Upper Motor Neurons
-superior colliculus |
-projects to medial cell groups in the cervical cord
-influences neck muscles -move head towards sensory stimuli -called the colliculospinal tract |
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Brainstem Centers of Upper Motor Neurons
-reticullar formation |
recieves input from highet motor cortex
-is a complicated network of circuits located at the core of the brainstem -a rod that ranges from the medulla-pons-midbrain -is important for posture -called the reticulospinal tract |
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Brainstem Centers of Upper Motor Neurons
-Red Nucleus |
-called red because it is surrounded by a rich capillary bed
-located in the midbrain -recieves input from the motor cortex and cerebellum -projects to lateral positions and intermediate zone in the cervical cord -involved in movement of arm muscles -called the rubrospinal tract |
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Feedforward processing
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-Able to predict changes in posture and generate an appropriate stabalizing
-often fire in anticipation to the actual need for an adjustment -the reticulospinal tract is key for this -If you inhibit this, the original muscle will still move, but the stabalizing muscle will not fire -ex. bicep anticipation will trigger gastrocnemius |
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Direct vs. Indirect pathways from the motor cortex
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Direct pathway
-goes to the ventral lateral spinal cord (white matter) Indirect pathway -synapses in the reticular formation, which subsequently goes to the medial |
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Primary Motor Cortex (1MC)
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-located in the precentral gyrus, adjacent to the Si
-Controls the contralateral side of the body Topographic organization -body represented across the medial-lateral axis -More space is given to areas of fine motor control -Multiple neurons can get the same muscle to contract and are not located all in the same place in the cortex -recieves input from the SI to incorporate for planning |
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Motor Feilds
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-A stimulation of a neuron in the primary motor cortex (1MC) will cause multiple muscles to fire, while inhibiting another group of muscles
-multiple neurons can get the same muscle to fite -Receptive feilds are based on organized movements, not on specific muscles -therefore, motor neurons can act upon more than one motor pool |
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Directional Tuning of Upper Motor neurons in the 1MC
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-activity of a single neuron recorded for the PMC is dependent on the direction of the future movement
-individual neurons are tuned too broadly to predict the direction of a movement -Must compare activity in a population of neurons to calculate direction |
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The Premotor Cortex (preMC)
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-lies adjacent(rostral) to the 1MC
-makes extensive reciprocal connections to the 1MC, and projects directly to the spinal cord -makes up 30% of axons in the corticospinal tract -contains the lateral preMC, involved in movement intensions |
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Lateral PreMC
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-has neurons that are tuned to a particular direction of movement like the 1MC does
-These neurons differ in that they fire earlier to pair movement with a visual cue -This is used for planning intentions before initiating the act -Lesion in monkeys prevents vision-conditioned tasks, though vision is fine |
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Medial PreMC
(top of brain before 1MC) |
-mediate the selection of movements
-responds to internal rather than external cues -Uses memory to select movements, not cues like the lateral preMC does -Neurons of the medial preMC will fire if just thinking about doing the movement |
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Modulation of movement by the Basal Ganglia
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-gets info to the spinal cord indirectly, by modulating upper motor neuron activity
-large set of nuclei that lie deep within the cerebral hemispheres -the caudate, putamen and globus pallidus are the the main nuclei -Form a loop in the brain with substantia nigra and the subthalamic nucleus to link most of the cortex to upper motor neurons |
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Corpus striatum
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"striped body"
-contains two of the main nuclei, the caudate and putamen, the two input zones of the basal ganglia -Most parts of the brain project here, esp the associational cortical areas of the frontal and parietal lobes: the corticostriatal pathway -recieving neurons are called medium spiny neurons and have large dendritic trees -medium spiny neurons integrate info from a variety of structures |
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Which areas do not project to the corpus striatum
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The auditory and visual cortex do not project to the corpus striatum (unlike most other parts of the cortex)
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Inputs to the caudate and Putamen (generalizations)
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-these inputs are excitatory glutamatergic synapses
-each spiny neuron can get synapses from lots of different cortical neurons -each cortical neuron also diverges and synapses on a few medium spiny neurons |
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Projections from Medium Spiny Cells:
-convergence? -use which nt? -project to..? |
-Are GABAergic (inhibitory)
-Terminate in a pair of nuclei within the basal ganglia called the Globus Pallidus (internal and external) AND on the pars reticulata in the substantia nigra(these are then the major output neurons) -more than 100 medium spiny cells converge onto one neuron in the globus pallidus |
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Globus Pallidus Output
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-Globus Pallidus internal neurons project to the ventral lateral and ventral anterior nuclei, VL and VA of the thalamus
-the thalamus then redirects back to the cortex to form a loop between the cortex and basal ganglia |
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Pars Reticulata Output
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-projects to upper motor neurons in the superior colliculus without going to the thalamus(unlike globus pallidus outputs)
-Are also GABAergic and maintain high levels of spontaneous activity for constant inhibition of movement |
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the Direct Pathway of medium spiny cells
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-MSNs will fire in anticipation of movement
-this inhibits inhibition that is normally making upper motor neurons stay quiet -now upper motor neurons can send commands to local circuit and lower motor neurons to initiate movement |
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The General Disinhibitory Circuit in the Basal ganglia to lower motor neurons
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-excitatory input to a MSN in the striatum will disrupt the tonically active output neuron(Globus Pallidus) from releasing GABA
-This will be a break from normal inhibition of the VA/VL nuclear complex in the thalamus -Now excitatory inputs that were previously cancelled out will cause the thalamus to excite the motor cortex -The motor cortex will excite lower motor neurons via upper motor neurons and local circuit and allow for movement **This is all due to transient ibhibition of a globus pallidus neuron |
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Neurotransmitters of the disinhibition pathway
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-The cortex uses excitatory glutamate on the putamen
-The MSN of the putamen use GABA on the internal globus pallidus -The internal GP uses GABA on the VA/VL nuclear complex of the thalamus -the thalamus uses Glutamate on the cortex -movement will occur if the GP stops releasing GABA for a moment |
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THe Indirect Pathways of the Medium Spiny Neurons
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-MSNs also project to the external Globus Pallidus neurons
-external GPs then project to the subthalamic nucleus of the ventral thalamus -the subthalamic nucleus can then project back into the internal GP (cutting back into the direct pathway) -This loop works as negative feedback to disinhibition. -Subthalamic projections are excitatory and cause GPs to start releasing GABA again so upper motor neurons don't get excited for very long. -once again the nts are glutamate and GABA **THis has the opposite effect of the direct pathway |
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What condition can result if the indirect pathway is not functional?
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Hemiballismus
-violent involuntary movements of the limbs -caused by defects in the subthalamic nucleus of the contalateral side -internal GPs are not excited by the STN to start releasing GABA again to the thalamus, and so the VA/VL inappropriately excites the motor cortex |
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What dopamine receptors do Medium spiny neurons going to the INTERNAL globus pallidus have?
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MSNs synapsing in the internal GP have D1 receptors, coupled with GaplhaS
-this makes them excitatory when dopamine binds -since the direct pathway has 2 GABA synapses (at MSN and GPN) they cancel out to give overall positive feedback to the thalamus (and on) |
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What dopamine receptors do Medium spiny neurons going to the EXTERNAL globus pallidus have?
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Use D2receptor for dopamine coupled with Galphai
-This inhibits the indirect pathway -there are 3 GABA synapses in this pathway(MSN,GPe,GPi) so their overall effect is to give negative feedback to the thalamus. -dopamine stops this negative feedback |
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How does Parkinson's disease interfere with the MSN pathways?
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-due to degeneration of dopaminergic neurons of the substatia nigra pars compacta
-dopamine pathways to activate the direct and inhibit theindirect pathway is diminished -the overall impact an overactive SNT that greatly increases the levels of tonic inhibition of the thalamus/motor cortex -->decreased excitation, causing slow movements and rigidity or extremes |
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How does Huntington's disease interfere with pathways
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-causes rapid deterioration of the caudate and putamen
-Leads to rapid, jerky movement |
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Non-Motor loops in the Basal Ganglia
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-occulomotor look for modulating Gaze
-Limbic Loop that may regulate emotional behavior and motivation (Tourette's may interfere here) |
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Inputs to the caudate
(2) |
-neurons here will fire in anticipation of eye movements
the caudate receives cortical projections primarily from: -association cortices -motor areas in the frontal lobe that controls eye movement |
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Inputs to the Putamen
(6) |
-neurons will fire in anticipation of body movements
the putamen receives cortical projections from: 1,2) the primary and secondary somatic sensory cortex 3) extrastriate visual cortex in the temporal and occipital lobes 4,5) premotor and motor cortex 6) auditory association areas in the temporal lobe |
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Non Cortical inputs to the Medium Spiny Neurons
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-From interneurons within the striatum itself
-From thalamic neurons which are inhibitory and synapse on the dendritic shaft -From the brainstem's dopaminergic substantia nigra pars compacta projections. -MSNs need many inputs to fire and are therefore usually silent |
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Modulation of movement by the cerebellum
general: info from? projects to? it's job? |
-the "little brain"
-like the basal ganglia, it does not have direct acces to lower motor neurons -gets projections from a wide area of the cortex -sends projections to the upper motor neuron centers (brainstem, cortex) -is 10% of brain's volume, but 50% of it's neurons: dense! -important for fine movement coordination, balance and muscle tone |
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What is the relationship of the cerebellum to the cortical motor area?
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-The cerebellum gets 40X more info than it spits back out (to relay nuclei and the thalamus)
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Anatomy of the cerebellum
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-has folia that runs horizontally
-has bilateral symmetry -has 3 lobes: anterior, posterior, Flocculondular lobes |
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What are the three parts of the cerebellum and how are they distinguished? where is each?
|
-based on their sources of input
1)cerebrocerebellum (lateral) 2)Spinocerebellum (medial) 3)vestibulocerebellum (flocculus and Nodulus) |
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Cerebrobellum
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-oppupies the lateral cerebellar hemispheres
-input from many cortex projections -especially well developed in primates -concerned with regulation of highly skilled movements, especially the planning and execution of complex temporal and spacial sequences |
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Spinocerebellum
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-located in the medial and intermediate aread of the cerebellum with vermis in the middle
-only part of the cerebellum that gets direct input from the spinal cord -lateral part concerned with distal muscles -vermis(central part) is concerned with proximal muscles and eye movements |
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Vestibulocerebellum
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-oldest part of the cerebellum (common to all verts)
-comprised of the floculus and the nodulus (tubing below the vermis) -recieves input from the vestibular nuclei in the brainstem -regulates movements underlying posture and equilibrium |
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3 zones of each cerebellum's
-cortex -Deep nuclei -Peduncles |
Cortex: cerebrocerebellum, Spinocerebellum and vestibulocerebellum
Peduncles: Superior, Middle, Inferior Deep Nuclei: Fastigial, Interposed, Dentate |
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brainstem and Diencephalon components related to the cerebellum
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-VA/VL complex of the thalamus
-pontine nuclei (pons) -Vestibular nuclei (medulla) -inferior olive (medulla) -Dorsal nucleus (spinal cord) |
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Superior Cerebellar Peduncle
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-mostly Efferent (away from cerebellum)
-Sends axons out to the upper motor neurons in the red nucleus and deep layers of the spinal cord -sends axons to the thalamus (and relay nuclei) to get to motor and premotor cortices and primary motor neurons |
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Middle Cerebellar Peduncle
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-Mostly an Afferent pathway (to the cerebellum)
-gets projections from pontine nuclei (which itself gets projections from almost all aread of the cerebral cortex and spinal cord) -To get to the middle peduncle, the pontine axons will cross the midline. This is why cerebellum is involved in control of the ipsilateral side of the body. -there are over 10 million axons in this tract! |
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Inferior Cerebellar Peduncle
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-contains both afferent and efferent pathways
-efferent: axons from the cerebellum use the inferior peduncle to get to the vestibullar nuclei and reticullar formation -afferent: cerebellum recieves info from the vestibular nuclei, spinal cord and brainstem tegmentum through the inferior peduncle |
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Inputs to the cerebellum
|
**the cerebral cortex is the major source
-motor and premotor areas -primary and secondary somatosensory -visual areas in the posterior parietal lobe (which are concerned with processing visual motion) |
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Output of the cerebellum
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-mainly to the motor and premotor cortex
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Purpose of the cerebellum
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-recieves huge amounts of info from the cortex and spits out only back to the motor and premotor areas.
-visually guided movements are the major task -the cerebral cortex lets the cerebellum know what movements were planned and ordered, and the output allows for motor error reduction by looping back to the planning |
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vestibular input
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-vestibular input from the 8th cranial nerve (hearing, balance)
-vestibullar nuclei in the medulla -remains ipsilateral from the point of entry (like spinal input) in the brainstem: right cerebellum is for right body (unlike cortex) |
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Dorsal nucleus of Clarke input
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- relay info from muscle spindles and other mechanoreceptors
-project to the spinocerebellum |
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Inferior Olive and locus coerulus
|
-are nuclei in the brainstem
-send input to the cerebellum for learning and memory of movements |
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What part of the thalamus relays info between the cerebellum and the motor areas of the cortex?
|
the ventral lateral complex
-cerebellar cortex--> Deep cerebellar nuclei--> VL complex--> motor cortex areas (in afferent pathways TO the cerebellum, pontine nuclei are used) |
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Output targets of the Cerebellum
|
-red nucleus
-vestibular nuclei -supperior colliculus -reticular formation -motor/premotor cortex |
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Granule cells
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-most numerous cell type in the brain
-give rise to parallel fibers that ascend to the molecular layer of the cerebellum. -Each granule cell connect to thousands of Purkinjes |
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Purkinje cells
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-each purkinje cell touches thousands of parallel fibers
-is also innervated by many contacts of a single climbing fiber (this modulates the purkinje cell's sensitivity to a granule cell -project to deep nuclei -are GABAergic |
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Input cells of the deep cerebral nuclei
|
Purkinje cells are inhibitory
-more involved in correctin behavior mossy fibers and climbing fibers also synapse the deep nuclei, but they are excitatory. |
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Functions of the cerebellum
What do defects cause? |
-vestibulo-ocular reflex
-conditioned reflexes (eye blink) -motor learning --> defect lead to ataxia |
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Cerebellum's role in
Vestibulo-ocular Reflex |
-fastest reflex in the brain
-still operates without cerebeullum, but only in constant conditions -adjusting to growth, change or damage requires the cerebellum -monkey glasses example -rabbit air puff example -VOR gain can reset to optical effects |
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How do you test a split brain?
|
-vision will go to the opposite side of the brain, so that the left visual field will be on the right side of the brain.
-If the corpus callosum is cut, a person cannot transfer this information of what is in thier left visual field from the right side of the brain to the left side, where speech centers are. -Split brains will say they see nothing on the left side. -this is not a problem for the right visual field, which will be redirected to the left brain, and need not pass the midline to be communicated. |
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TEA, tetraethylammonium
vs. TTX, tetrodotoxin |
TTX-blocks inward current (Na+) but not outward current (K+)
TEA- will block outward current (K+), but not inward current -will not get both a depolarization and a hyperpolarization if you use one of these |
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Why do APs exhibit an all or none threshold?
|
At potentials below the threshold, not enough Na+ channels open to raise the potential high enough to open more channels (signal dispersed by diffusion if enough channels in next portion of axon do not open)
-at potentials above threshold, the action potential cycle is activated and maintained |
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Why do APs exhibit undershoots?
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-the potassium cycle is slower, so at some point Na+ channels are closed, while K+ channels are still open and + charge is leaving the cell. More K+ is flowing out than at rest, when K+ leak channels are open, but voltage gated ones are not.
-Hyperpolarization will occur and will inactivate the K+ channels *this, along with closed Na+ channels, creates a refractory period -K+ leak channels(K+ going in now) and transporters bring the cell back to resting potential |
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How can you increase the rate of AP formation? (speed it up)
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1) increase diameter of the axon: less resistance in axon
2)Insulate the axon to reduce current leak. Myelin does this. -can't insulate the whole axon b/c channels are neccessary to have ion flow. APs are "saltatory" -channels are only at rodes of ranvier, so APs jusmp between them |
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The Cerebral Hemispheres Contain
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cortex:grooves (sulci) and gyri
subcortex: -basal ganglia- control of fine movement -amygdala- social behavior and expression of emotion -hippocampus- memory |
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10 stages of synaptic transmission
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1) neurotransmitter is synthesized and packages into vesicles
2)An action potential arrives at the presynaptic terminal 3) depolarization causes opening of voltage gated Ca++ channels 4) There is an influx of Ca++ (hugggee chemical gradient so it rushes in very fast) 5)Ca++ causes vesicle to fuse with the membrane 6)Neurotransmitter is released into the synaptic cleft 7)Transmitters bind to receptors in the post synaptic cell 8) This opens of closes channels on the post synaptic membrane 9) Current flows inside the postsynaptic cell, possibly causing an AP 10) Retrieval of membrane via endocytosis (and of neurotransmitter) |
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how does Snap-25 mediate vesicle fusion?
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*t-snare snap-25 mediates the winding of v-snare synaptobrevin with t-snare syntaxin when [ Ca++ ] is high enough
*[Ca++] is sensed by synaptotagmin on the vesicle |
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Tetnus
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cleaves synaptobrevin ( a v-snare) to prevent vesicle fusion
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Botulinum toxins (botox)
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cleaves syntaxin and snap 25, the t-snares on the target membrane
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Alpha- latrotoxin
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-black widow poison
-causes massive exocytosis of vesicles without any [Ca++] requirement - thought to effect the calcium sensor synaptotagmin |
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Criteria that defines a neurotransmitter
(4) |
-Must be present in the presynaptic neuron
-must be released in response to a depolarization -Must be calcium dependent -The must be specific receptors for it localized on the post-synaptic cell -It does not have to be exclusively a neurotransmitter and may have other functions (like ATP, glutamate, glysine) |
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Which neurotransmitters have transporters for reuptake?
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-Glutamate (on presynaptic terminal and on glial cells to make it into glutamine)
-GABA (on term and glial cell) -Norepinephrine (the transporter is a target for amphetamines) -Serotonin (target for prozac) |
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Which neurotransmitters are degraded by enzymes?
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-Acetylcholine: by Acetylcholine esterase, AChE
-Histamine: by Monoamine oxidase. MAO (like benedryl) -Peptide Neurotransmitters : by pepsidases |
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Act exclusively by GPCRs
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-catecholamine receptors
-neuropeptides |
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Purinergic receptors
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-ATP is excitatory and in all cells
-3 classes: 1 ion, 2 GPCR -ionotropic- only 2 tm regions! -2 GPCR- one likes adenosin, the other ATP |
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Criteria that defines a neurotransmitter
(4) |
-Must be present in the presynaptic neuron
-must be released in response to a depolarization -Must be calcium dependent -The must be specific receptors for it localized on the post-synaptic cell -It does not have to be exclusively a neurotransmitter and may have other functions (like ATP, glutamate, glysine) |
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Which neurotransmitters have transporters for reuptake?
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-Glutamate (on presynaptic terminal and on glial cells to make it into glutamine)
-GABA (on term and glial cell) -Norepinephrine (the transporter is a target for amphetamines) -Serotonin (target for prozac) |
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Which neurotransmitters are degraded by enzymes?
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-Acetylcholine: by Acetylcholine esterase, AChE
-Histamine: by Monoamine oxidase. MAO (like benedryl) -Peptide Neurotransmitters : by pepsidases |
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Act exclusively by GPCRs
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-catecholamine receptors
-neuropeptides |
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Purinergic receptors
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-ATP is excitatory and in vesicles
-3 classes: 1 ion, 2 GPCR -ionotropic- only 2 tm regions! -2 GPCR- one likes adenosin, the other ATP |
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Serine/ Threonine Kinases
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PKA- tetramer with 2 regulatory subunits and two catalytic subunits. cAMP binds the regulatory subunits and releases the catalytic ones to go phosphorylate target proteins
CaMKII- Ca/Calmodulin-dependent protein kinase. Thought to act as a memory molecule. PKC- activated by DAG and Ca++ (released by PI3 binding a Ca++ channel). |
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Protein tyrosine Kinases
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1) Receptor tyrosine kinases- Eph receptors and growth factors
-MAPs(also kinases) are often downstream 2)cytoplasmic kinases-many oncogenes -are particularly key in cell growth and differentiation |
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Transcription Factors
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-often found at the end of nuclear signaling pathways
-are proteins that interface with RNA polymerase to select the promotor regions of a gene ex's: C-fos and CREB |
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CREB
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-"cAMP response element binding" protein
-phosphorylation activates it and it activates transcription - can be phosphorylated by: 1) PKA 2)CA++/calmodulin kinase IV 3)MAP kinase |
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Neural Growth Factor
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the first step to all of these is an NGF dimer causing homodimerization of a receptor tyrosine kinase
PI3 kinase-->Akt-->cell survival ras--> ras/gtp-->MAP kinases or PLC-->PKC activation both cause neurite outgrowth and differentiation |
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What is long term depression in Cerebellar Parallel fiber synapses?
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the purkinje cell a parallel fiber is about to synapse on has AMPA and mGluR
-AMPA opens and excites cell -mGluR activates a signal transduction pathway that feeds back to decrease the activity of AMPA -long term depression: the same stimulus will have less impact after this |
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How does intracellular calcium caused by an AP opening voltage gated Ca++ gated channels impact Tyrosine Hydroxylase?
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-not only does intracellular calcium cause vesicle fusion(short term) , but it also activates protein kinases (long term)
-Ca++ dep. protein kinases will phosphorylate tyrosine hydroxylase, the rate limiting enzyme in catecholamine production -Increased catecholamine synthesis causes more to be released and a larger post-synaptic response |
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Order of conduction velocity from sensory afferents
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fastest:
proprioception: Ia, II Touch: AB First Pain, temp A-Delta Second Pain, temp, itch C fiber slowest |
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Meissner's
-adapt fast or slow? -% innervation of hand? -receptive field size? -location? |
-the one that looks like a q-tip
-between dermal papillae (in epidermis) -Adapts fast -low threshold -has small receptive feilds -40% of hand |
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Pacinian Corpuscles
-adapt fast or slow? -% innervation of hand? -receptive field size? -location? |
-the one onion-amoeba one
-Adapts fastest -low threshold -10-15% innervation -large receptive feilds -Good at discrimination of fine surfaces -stimulation induces a tickle/vibration -onion like filter filters out all but high frequency stimulation |
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Merkel's Disk
-adapt fast or slow? -% innervation of hand? -receptive field size? -location? |
-the ones in the ones in the epidermis grooves
-25% of hand innervation -particularly dense in fingertips, lips, genetalia -adapt slow -feeling of light pressure -small receptive fields |
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Ruffinis's
-adapt fast or slow? -% innervation of hand? -receptive field size? -location? |
-the skinny Footballs
-lie parallel to skin in the dermis -20% of hand -adapt slow -large receptive fields -detect cutaneous stretch |
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2 point discrimination test can depend on...
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-density of mechanoreceptors in the area
-degree of convergence at the level of the 2nd order sensory neuron -lateral inhibition can make borders more discreet: *response is proportional to stimulus in first order neurons *the neuron closest to the stimulus will inhibit its adjacent neighbors -don't forget the CNS is also used for discrimination: practice can help |
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The somatic sensory components of the thalamus
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-the ventral posterior complex (VPC) contains the VPL and the VPM
VPL: gets all projections from the medial lemniscus for somatosensory and proprioception info VPM: recieves all trigeminal info from face (cranial nerve 5) -The VPC has a complete representation of the body -all VPC axons project to layer IV of the somatic sensory cortex |
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Where does the primary somatosensory cortex send projections?
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-SI projects to SII, which projects to amygdala or hippocampus to associate feeling and memory
-SI projects to Parietal areas 5 and 7 that can go to motor and cortical areas in the frontal cortex from there. |
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3 types of nociceptors
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-AS mechanosensitive
-AS mechanothermal -C fiber polymodal (no myelination) |
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What is the difference between a thermoreceptor and a Nociceptor for temperatures?
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- nociceptor will not fire until the temperature is dangerous (painfl)
-other thermoceptors fire at all temperatures at the same frequency |
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TRP channels
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-"transient receptor potential"
-Ion channel receptors -open in response to heat or capsaicin -open to allow in Ca++ and Na+ for an AP inward current (non-selective cation channel) -VR1 mutation causes mice to drink capsaicin with no reaction |
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Two types of Pain by two fibers:
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-first sharp pain: AS fibers
-second, dull, long lasting pain: C fibers |
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Hyperalgesia
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-enhanced sensitivity and pain response to the area around damaged tissue (like sunburn)
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Hyperalgesia is due to release of these 5 substances by damaged cells
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-prostoglandins
****blocked by asprin and ibuprofen because they inhibit cyclooxygenases, necessary for prostoglandin synthesis -bradykinin -Histamine -serotonin -ATP ***can interact with TRP channel to make them easier to open |
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Spinothalamic tract
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-cell bodies most lateral in the DRG
-innervate dorsal horn (some of these project into spinal cord for reflexes) -other neurons cross the midline at the segment and go up to the VPC via the antherolateral column |
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what is responsible for the emotional aspects of pain?
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-the VPC (thalamus) projects to the reticullar formation and interlaminar nuclei of the thalamus to get to the limbic system
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Pain and Temp from face
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-enter at the level of the mid pons
-travel DOWN via spinal trigeminal tract to get to the spinal nucleus in the Medulla, where cross over occurs -Now, the info can go UP on the Trigemino-thalamic tract to the VPM |
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Referred Pain
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-viseral pain does not have it's own neurons in the dorsal horn.
-this info is conveyed by hitting a random second order nociceptor assigned to get inputs from skin -the pain will seem to be coming from this skin input |
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Gate theory of pain
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-this is why rubbing an injured area can dampen the dull late pain (Cfibers)
-An AB fiber (mechanoreceptor) and a C fiber will be sending messages through the dorsal horn at the same time when the AB heads to the dorsal column and the C fiber heads to the antherolateral system. -The AB fiber can inhibit the C fiber's ascending message with inhibitory interneurons |
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What part of the brain can be stimulated to reduce pain sensation while leaving other senses intact?
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-the periaqueductal gray matter (in midbrain) or rostral medulla (raphe's nuclei and reticullar formation) can be stimulated because they project to the dorsal horn to inhibit ascending pain fibers
-similar to gate theory, but in this case, inhibition of the ascending pain is by a *descending* projection -this works when descending inputs from brain (ex. Rache nucleus) synapse on interneurons that contain enkephanlin, an opiod, that can inhibit C fibers |
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Opiods
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-receptors are metabotropic and expressed in areas of the descending pain pathway
-naloxone is an antagonist -opiods decrease the chances that a nociceptor will fire by hyperpolarizaing |
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Light is focused in two ways:
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-a fixed lens: the cornea and a flexible lens, the ciliary muscles
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which cells in the retina produce graded responses and which ones produce APs?
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-rods, cones, bipolar cells and horizontal cells are graded
-ganglion cells are the output cells and give APs -this is because the ganglions are the only ones that travel long distances to make APs necessary |
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Photoreceptor
in the light vs. in the dark |
in the dark: relatively depolarized at -40 mV and has high levels of cGMP to ope Na+ channels
in the light: signal transduction breaks down cGMP into GMP and Na+ channels close, causing hyperpolarization |
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How does calcium in photoreceptors prevent saturation?
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during resting (relative depolarizations), Ca++ comes in through cGMP gated cation channels. It normally:
1)inhibits rhodopsin kinase 2)inhibit gaunylyl cyclase when the levels of calcium drop due to fewer channels being open during hyperpolarization, there is less intracellular Ca++. this causes: 1) more rhodopsins to be inactivated by arrestin 2)More GTP to get turned into cGMP and reopen some channels |
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Rods vs. Cones
adaptation response sensitivity convergence location |
-Rods produce a rxn to one photon, while cones need over 100
-Cones adapt better than rods Rod circuit: Rods--> rod bipolar--> amacrine cell-->cone bipolar or ganaglion cone circuit: cones--> bipolar-->Ganglion -Rods exhibit convergence: many rods onto a bipolar, many bipolars onto an amacrine cell -cones can be 1:1:1--> good acuity -cones in middle, rods in periphery |
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how do cones get color vision?
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3 opsins: blue (short wavelength cones), green (M-cones) and red (L-cones)
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Notes about RGC firing
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-There is a spontaneous level of activity
-on center or on surround -one spot can be modulated by multiple receptive feilds -firing rate is based on the RATIO of center to surround, not the multiple |
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2 types of bipolar cells and their receptors
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On center: (on hyper!!!!)
-uses mGluR that cause Na+ channels to close and *hyper-polarize* the cell in response to glutamate off center: -uses AMPA receptors that cause the cell to depolarize in response to glutamate |
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on center vs. off center bipolar cells in the dark:
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-More Glutamate being released from photoreceptors
-AMPA off center cells are depolarized in the dark -mGluR on center cells are hyperpolarized in the dark |
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how do on-center bipolars connected to an on-center cone in light change the amount of APs on center RGC fires?
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*less glutamate released to bipolars (one of each type will synapse with a cone)
ON CENTER: where normally hyperpolarized (inhibited) in response to basal glutamate release. -less glutamate, less hyperpolarization, increased firing to ON CENTER RGCs |
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How do off-center bipolars connected to an on-center cone in light change the amount of APs an off center RGC fires?
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*less glutamate released to bipolars in the light
OFF center: AMPA will get less glutamate and will depolarize less. This decreases the graded signals(glutamate) the bipolar gives to off center RGCs and will decrease firing. |
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Horizontal cells
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-release GABA in response to glutamate
-horizontal cell will be hyperpolarized |
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What regions do the optic tracts (after chiasm ) project to?
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-Mostly the Lateral Geniculate nucleus of the thalamus
-Also the superior colliculus (for head eye movement) -also the pretectum (for pupillary light reflex) -also the suprachiasmatic nucleus (for control of circadian rhythms) |
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Which layers of the LGN are for the left eye and which are for the right?
(hint: it takes a bigger person to be wrong, left) |
layers 1,4,6= left , "wrong" :1+4+6=11
layers 2+3+5=10, smaller, right |
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What route does info of the superior visual feild take to the visual cortex from the LGN?
-How about the inferior visual field? |
Meyer's loop
-the inferior retinal info (superior visual field) loops down into the temporal lobe -the superior retinal info (inferior retinal field) loops above the LGN though the parietal lobe. |
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How is the map of the visual field distributed across the occipital lobe's visual cortex?
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-the visual field (due to the retina) is flipped and inverted on the visual cortex map.
-the fovea is represented the most posterior part of the occipital lobe (and cortex!), with periphery more anterior -upper and lower visual field are divided by the calcarine sulcus |
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Dorsal stream pathway
(door slammed in your face) |
-motion detection:
V1-V2-MT :middle temporal area (parietal lobe) -spatial analysis |
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Ventral stream pathway
(a brightly-painted vent) |
-V1-V2-V4 :inferior temporal lobe
-color and object recognition |
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What is the neural circuit for pupillary light reflex?
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-light hits retina, and both sides of the brain get a signal about it from one eye (b/c of temporal nasal division to sides)
-RGCs send signal to pretectum -pretectum projects contra and ipsi to the Edinger westphal nuclei in the midbrain -Ed/West projects to ciliary ganglion (PNS) -ciliary ganglion projects to the constrictor muscle of the iris |
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How far is the visual map maintained until the left and right visual fields are merged?
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-maps are maintained all the way to the V1
-2 sides finally merge though the corpus callosum |
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Do dLGN neurons have center and surround receptive fields?
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yes. Each receives input from 1 or 2 RGCs and therefor inherit this system from them
-are also either on or off.` |
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How else (besides right or left eye source) are the layers of the LGN organized?
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1,2= magnocellular pathway (m channel)
3,4,5,6=Parvocellular (perv) pathway More perves, smaller cells, like to wear bright colors |
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what is the input and output layer of the striate cortex
|
LGN projects to layer IV (iput layer)
-output comes out of layer V (peace out output) -layer IV is still monocular, and is used to set up dominance columns -other layers are binocular |
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how are the receptive fields of the visual cortex set up? Are they center surround?
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No (center surround ends after LGN)
*2 Cell types of the Visual cortex Simple cells only respond to a certain angle orientation and have surround inhibition to other orientations. Complex cells have big receptive fields detect movement. Do not on-off or prefered orientation -prefered orientation is organized into columns and are set up in repeating units |
