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159 Cards in this Set

  • Front
  • Back
What is physiology
1. The study of the function of living organisms
2. How animals maintain equilibrium- (i.e. ion balance, temp, response to environmental change)
3. Focus: molecular-> organismal level of organization
4. Physiological processes are based on chemical and physical laws- i.e. ohm's law
5. Physiology= phenotypic response to genes and environment
Evolutionary Trends in the Nervous System
1. Nerve Net- diffuse network of neurons- no functional specialization (afferent/efferent/interneuron all the same) i.e. hydra
2. Ganglia- cluster of connected soma that act as integrating centers- most bilateral animals (i.e. insect, leech)
3. Cephalization- anterior concentration of sensory neurons and receptors and associated cluster of ganglia (= brain)
4. More complex structures were added to more primitive structures (mammalian cortex)
5. Relative size of brain region correlates with relative importance (i.e. fish have small cerebrum big optic lobe, we have huge cerebrum)
6. Larger animals have bigger brain -> birds and mammals have a larger brain relative to body size
Central Nervous System
Most motor somata; all interneurons
-Nuclei: collections of somata of similar function
-Tracts: bundles of axons extending from particular nuceli
Peripheral Nervous System
Axons of sensory and motor neurons; ganglia of somata for some autonomic neurons and most sensory neurons
- nerves= bundles of axons
Spinal Cord
-Reflex behaviors; patterned locomotion
-Segmented: cervical (above ribs), thoracic (ribs), lumbar (below ribs), sacral (pelvis)
-Cerebrospinal Fluid:
-surrounds brain and spinal cord within meninges
- flows through central cavity and cerebral ventricles

-Contains white matter and grey matter
Functions of CSF
1. waste removal
2. shock absorber- cushion from damage
3. nutrients
4. hormone transport
5. reduces pressure on bones and other organs
White Matter
outer myelinated axons
Grey Matter
inner non myelinated somata and dendrites
Dorsal roots ganglia
-somata of unipolar afferent nerves
-associated with sensory info coming in
dorsal horn
terminals of sensory afferents; synapse with interneurons or efferents
-associated with sensory info coming in
ventral horn
motor somata
-associated with motor function going out
ventral roots
efferent spinal nerves
-associated with motor function going out
Brain
-coordinates entire body
-develops from 3 primary vesicles in the neural tube: forebrain, hindbrain, and midbrain
-primary vesicles subdivide into 5 secondary vesicles
Neurulation
development of neural tube from ectoderm- nervous system derived from same tissue that skin is derived from
Hind Brain
Reflex responses, involuntary behaviors (i.e. breathing, posture)
- includes medulla oblongata, cerebellum, and pons
Medulla Oblongata
-autonomic function- respiration, b.p., heart rate, digestion
-some cranial nerves control neck and facial muscles
-pathways b/w the spinal column and brain
Cerebellum
-Motor coordination, learning, motor skills
-integrates input from eyes, ears, muscles w/ motor signals from forebrain
-damage results in cerebral palsy
Pons
-connects cerebellum and medulla to forebrain
-dorsal section- regulates respiration, taste, and sleep
Midbrain
-coordinates reflex responses to auditory and visual stimuli; greatly reduced in mammals
-includes tectum and tegmentum in non mammalian verts
-in mammals- superior and inferior colliculus
Tectum
roof of midbrain in non-mammalian vertebrates
-coordinates input from ears and eyes
Tegmentum
-fine motor control
-substantia nigra= nucleus within tegmentum associated w/ dopaminergic signalling
Superior/Inferior Colliculus
part of midbrain of mammals, derivative of tectum
superior- visual map
inferior- auditory map
Forebrain
-processing of olfactory signals, regulating body temp, reproduction, emotions; learning and memory
-consists of limbic system and cerebral cortex
Limbic System
Phylogenetically primitive structures; expression of emotion, motivated behavior, and some memory
Hippocampus
temporal and spatial processing
- consolidation of working memory
Amygdala
processing of emotional memories- esp. aggression and fear
-olfactory memory- (bruce effect)
Thalamus
Coordinating sensory and motor signalling- filter of sensory information
Hypothalamus
Integrates neural and endocrine system
-regulates body temp, body weight, sexual behavior, b.p, and thirst
Cerebral Cortex
Relative size of sub regions corresponds w/ relative importance
-includes sensory cortex, motor cortex, and association cortex
- in primates- assoc cortex the largest
Sensory cortex
primary visual, auditory, and somatosensory-> series of maps on layers of cortex
Motor cortex
controls voluntary muscle movement-> spatial distribution corresponds to muscle location
Association cortex
Memory storage, thought, communication, planning ( more complicated cognitive processing)
General Trends in the Cerebral Cortex
-Spatial distribution of neurons correlates w/ locations of muscles or body parts controlled by those neurons
-Space in the brain is organized in a strict somatotopic map in which space is allocated according to the relative importance of incoming sensory information-i.e. somatosensory cortex of star-nosed mole
Functional components of the sympathetic ANS
1. Active, frightened state (fight or flight)
2. Increased heart rate, respiration, b.p, skeletal muscles
3. Reduced digestion
Structural aspects of the sympathetic ANS
1. Pre-ganglionic somata in thoracic and lumbar
2. most synapses in sympathetic chain ganglion
3. long post-ganglionic axons
4. Pre- ganglionic neuron = cholinergic
post-ganglionic neuron = adrenergic (epinephrine/ norepinephrine)
Functional components of the parasympathetic ANS
1. Relaxed, sleeping state
2. Increased digestion
3. Decreased heart rate and respiration
Structural components on the parasympathetic ANS
1. Pre-ganglionic somata in brain and sacral segments
2. Synapses near target organ
3. Short post-ganglionic axons
4. Pre/post-ganglionic neuron = cholinergic
Neuron
a nerve cell; communicates information using chemical and electrical signals
Parts: soma, dendrites, axon, axon hillock, axon terminal
-morphology not always the same!- variety of lengths of processes
Dendrites
Receive incoming signal from other neurons and carry them toward the soma (graded potentials)
Axon Hillock
Site of signal integration that determines whether an A.P will occur
Axon
Transmits action potential to terminal
- evolved to carry w/ without loss of signal strength
Axon terminal
Site of synapse formation
-allows signals to be sent simultaneously to many other neurons, glands, or muscle fibers
Action Potential
All-or-none depolarization of a neuron membrane used to transmit signals along axons
-generally inside is more negative
- does not degrade over distance
- If signal strong enough at axon hillock- A.P will occur
-Voltage across plasma membrane rapidly rises and then falls
-neural, muscular, sensory, and some secretory cells
-depends on:
1. electrochemical gradients generated by Na+/K+ pump
2. open volatage-gated, ion-selective channels
Synapse
Site where information is passed between neurons; consists of a presynaptic and postsynaptic neuron
-Signal alternates b/w action potentials and graded potentials
Afferent Neuron
Neuron that carries sensory information from the body to the CNS
Interneuron
Carries info b/w neurons within the CNS
Efferent Neuron
Carries info from CNS to muscles and other organs (motor)
Neural Circuit
Afferent + Efferent Neuron and all the interneurons in between
Multipolar Neuron
Multiple processes extend from soma; most common type of vertebrate neuron (i.e. motor neurons)
Bipolar neuron
2 processes: one carries signal to cell body (dendrite) one carries signal away (axon)
-uncommon (i.e. retinal cells)
Unipolar Neuron
1 process from cell body branches as axon (ie. some sensory neurons)
Glial Cell
Support cells
-fill the space between neurons
-generally do not produce APs
-4 kinds: Oligodendrocytes, Schwann Cells, Astrocytes, Microglia
Oligodendrocyte
Kind of glial cell providing support and myelination in the CNS
Schwann cells
Kind of glial cell involved with myelination in the PNS
Myelination
Insulation that wraps around axons allowing faster transport
-differs in CNS vs. PNS
Astrocyte
Kind of glial cell- very actively involved in signalling
- removes ions and neurotransmitter at the synapse
-nutritive function
-forms blood-brain barrier (tight junctions)
-radial glia: direct early development of neurons
-Produce neurotropic factors (i.e. BDNF- brain derived neurotrophic factors which help encourage cell division, growth and survival)- promising treatment for Alzheimers!
Microglia
Type of glial cell that provides neuronal maintenance in the CNS (like macrophages)
-pick up waste products
Electrical potential (V)
Potential work that may be performed if two charged particles come together (volts)
-Negative work done if oppositely charged particles come together (electrostatic force attracts opposite charges)
-1 Volt= force required to move 1 Amp (positive charge) through 1 Ohm resistor
Current (I)
Movement of positive charge past a point per unit time (amps)
Resistance (R)
Hindrance to electric charge movement through a conductor (ohms)
(i.e. from an insulator - resistor= cytoplasms, plasma membrane (lipids)
Ohm's Law: V= IR
Conductance (g)
Reciprocal of resistance (R=1/g)
-measure of how easy it is for charge to move
Ohm's Law I=Vg
Capacitance (C)
Amount of electrical charge stored for a particular electrical potential (farads)
-how much charge can be stored on either side of an insulator
-C dictates the shape of change of Vm
-Higher capacitance reduces the rate at which Vm responds to a change in I
Membrane potential (Vm)
Electrical gradient across a cell membrane
Vm=Vin-Vout
Recording techniques:(used to determine membrane potential)
-intracellular
-extracellular
-patch clamp
Resting potential (Vrest)
Steady inside- negative potential when no action potentials or postsynaptic potentials are occuring
(generally negative charged)
-most membrances are polarized with an inside-negative Vrest (-20 mV to -100 mV)
Depolarization
Inside of cell becomes less negative
-can be produced by a positive pulse from current electrode
-can trigger an AP
Hyperpolarization
Inside of cell becomes more negative
-can be produced by a negative pulse from current electrode
-cannot trigger an AP
Passive electrical properties
Physical properties of the cell (capacitance, resistance) that determine the graded movement of electrical signals
Active electrical properties
Properties of some cells that allow them to generate action potentials (i.e. opening and closing of ion channels)
Non-gated ion channels
Open most of the time, determine Vrest
-i.e. K+ leak channel, Na+ leak channel
Voltage-gated ion channels
Open with change in Vm- Vm changes with either graded potential or neighboring AP
-thus responsible for AP!
Rising phase of AP- voltage-gated Na+ channels open
Falling phase of AP- voltage-gated K+ channels open
Ligand-gated ion channels
Open when specific molecule binds
-specificity important!
-found at synapse- neurotransmitter= example of a ligand
Phosphorylation-gated ion channels
Open in response to phosphorylation
-2nd messenger cascades- phosphate attached to inside of channel
Capacitor
two conductors separated by an insulator; stores potential energy by separating charge
-plasma membrane acts as a capacitor! -> lipid bilayer = insulator and cytosol and extracellular fluid = conductors
-Amount of charge stored on capacitor is proportional to its area- more current required to change Vm on larger cells (takes longer b/c need to decharge capacitor
Resistive current (Ir)
Flow of ions through channels
-changes Vm
Capacitative current (Ic)
Flow of ions that change the net charge stored on the membrane- needed to decharge the capacitor
Time Constant
t=RmCm
-time it takes for Vm to reach 63% of its final value
-Longer t indicates slower change in Vm
Why is t important?
-longer t- change in voltage lasts longer!
-small t- graded potential begins and decays rapidly -> thus less likely to have temporal summation and less likely to reach threshold -> AP
What maintains Vm?
1. Na+/K+ pump- active transport
2. Non-gated ion channels- selectively permeable
Equilibrium potential (Ex)
Vm when concentration gradient is balanced by the electrical chemical gradient
-starting point needs to be in a difference in concentration (concentration gradient)
-conc gradient opposes force gradient (electromotive force (emf))- reaches equilibirum
Nernst Equation
Equilibrium potential (Ex) depends on temperature (T), charge of ions (z) and the concentration of ions inside and outside the cell
Ex= RT/zF ln [X]o/[X]i
At 18 deg C Ex =0.058/z log[X]o/[X]i
-designed for working at 1 ion at a time ( K or NA)
Dynamic steady state
equilibrium maintained by constant exchange of ions across membrane ( non-gated channels)
Goldman equation
Extension of Nernst equation to multiple ions; P = relative permiabilities
What does Vrest depend on?
1. ion permeability
- K+ and Na+ are most important ions
-K+ is more permeable than Na+ b/c at rest more K+ channels are open than Na+ channels
-thus Vrest will be nearer to Ek+ than Ena+
2. ion gradients
-at rest, strong electrical gradient driving Na+ into cell (b/c not as permeable!)
-at rest, Na+ gradually leaks into the cell and K+ leaks out of cell

What prevents this leak from depolarizing the cell?
-Na+/K+ pump!- maintains the membrane potential
-3 Na+ out for 2 K+ in
-more + charge out than in
-if Na+/K+ pump is blocked- drop of Vm to 0mV
Threshold Potential
Voltage just sufficient to trigger an action potential
- relates to # of channels
-where spike occurs (generally around -40 mV) when voltage-gated channels open
Steps in AP
1. At rest- non-gated (leak) Na+ and K+ channels maintain Vm
2. Depolarization- voltage-gated Na+ channels open, inward Na+ current
-drives Vm-> Ena+ (+55)- gets to about +40
-positive feedback loop- increased depolarization opens more Na+ channels (triggering effect)
-voltage gated K+ channels open slowly (not much an effect initially)
3. Repolarization- Na+ channels close
-voltage-gated K+ channels remain open (outward K+ current)
4. After hyperpolarization- voltage-gated K+ channels remain open- driving Vm toward Ek+
-K+ channels close and restore Vrest
Absolute refractory Period
Period during repolarization when a second AP cannot be triggered
-Inactivation of Na+ channels
-adaptive feature
Relative refractory Period
period during after-hyperpolarization when second smaller AP can be triggered
-voltage gated Na+ channels can be triggered
-Voltage-gated K+ channels still open
Accommodation
AP threshold increases in response to continuous current
-constant stimulus- causing more stimulus to get an AP
-negative feedback type loop
1. Phasic response: rapid accomodation after 1-2 APs
2. Tonic response: gradually decreasing frequency of APs
- a type of neuroplasticity
-less frequent pulses
-does not happen in all cells!- rare phenomenon- generally happens when overstimulated
Selectivity filter
portion of ion channels that determines which ions pass through
a. ion size
b. ion charge
c. ease of dehydration

-charged amino acids inside channel- thus ion charge is important
-Na+ has more H20 molecules attached than K+ making it bigger and needing a larger channel
Ion Channels
1. Voltage-gated Na+ channels have activation and inactivation gates
-inactivation gate responsible for absolute refractory period
-rising phase of AP
2. Na+ channel structure:
-single large alpha protein with 4 transmembrane domains
-associated with multiple beta subunits
-low diversity: 11 isoforms in mammals, 2 isoforms in Drosophilia
(isoform = different forms of large protein structure- quaternary struc)
3. K+ channel structure
-4 alpha subunits-extracellularly
-4 beta subunits- intracellularly
-narrow transmembrane segment acts as selectivity filter
-high diversity ( 18 genes in mammals; 40 isoforms of alpha subunit in humans)-> diverse functions
Length Constant (lambda)
lambda = sqrt(Rm/Ri)
Rm= membrane resistance
Ri= cytoplasm resistance

-measures the distance over which an electrotonic potential shows a 63% drop in amplitude
-potential travels greater distance if lambda is larger
-refers to graded potentials within a segment
Ways of increasing lambda
1. increase membrane resistance (Rm) through myelination
2. Reduce Ri (also known as Rc)- giant axon- larger the radius, bigger the lambda
Myelin
Layers of membrane around axons (glial cells)
-increase Rm and decrease Cm
- increases length constant allowing electrotonic current to flow farther
-more rapid flow of AP
Nodes of Ranvier
unmylinated gaps where AP is produced
- myelin is segmented to prevent current from completely decaying
-saltatory conduction: discontinuous AP
-mutation of myelin basic protein (MBP) used as model of MS -> w/o myelination- signals down axon much slower and signals end up in wrong place
Electrical Synapse
direct coupling b.w pre and postsynaptic neurons
-not as common as chemical synapse
-faster than chemical synapse, but little flexibility (little plasticity)
-examples: retina, smooth muscles, cardiac muscles (places where you want constant regular contractions)
2 types:
- rectifying: current flows in one direction
-non-rectifying: current flows in both directions
Gap junctions
protein channels at electrical synapse
Ionotropic (fast) chemical synapse
1. voltage-gated Ca2+ channels open in presynaptic terminal
2. synaptic vesicles release neurotransmitter into synaptic cleft
3. Neurotransmitter binds post-synaptic ligand-gated channel
4. Current flows into post-synaptic terminal
5. Transmitter removed and membrane recycled through endocytosis
Metabrotrophic (slow) chemical synapse
1. Neurotransmitter binds to extracellular portion of receptor
2. Activates G protein bound to intracellular side of membrane
3. G protein directly or indirectly (second messengers) changes conductance through ion channels
Ionotropic vs. Metabotropic
Ionotropic: short signals (ms), small molecules synthesized at axon terminal, pre-synaptic release at active zones

Metabtropic: long signals (sec-hrs), larger molecules usually synthesized in soma, many sites of neurotransmitter release
Neuromuscular Junction
1. AP depolarizes the presynaptic terminal
2. Voltage-gated Ca2+ channels open; Ca2+ enter pre-synaptic cell
3. ACh release into synaptic cleft
4. ACh binds to receptor on endplate
5. ligand-gated channels open -> Na+ flows in, K+ flows out
6. Graded endplate potential (epp)
7. Acetylcholinesterase breaks down ACh to stop epp (otherwise constant muscle contractions would occur)

-rather than axon hillock being point of integration- integration occurs at junctional fold
i.e. myasthenia gravis- autoimmune response to ACh receptors -> low receptor number -> muscle weakness
Treatment= acetylcholine esterase inhibitors
Reversal potential (Erev)
Vm at which no current flows through ion channels even though they are open
-occurs when Vm=Ex for all ions that determine Vm
-used to determine which ions carry postsynaptic potential and which ions flow through ion-gated channel
-Erev for frog NMJ lies b/w Ek and Ena- indicates that both ions are flowing through
Excitatory postsynaptic potential (epsp)
-change in Vm that increases the probability of an AP
-Erev > threshold
-usually inward Na+ or Ca2+ current
-depolarizing current
i.e. ACh at frog NMJ, Vrest= -90 mV, Erev = 0mV (both Na+ and K+ flow), threshold = -55 mV --> depolarizing effect
-since Erev> threshold -> excitatory
* a particular channel always has the same Erev *
Inhibitory postsynaptic potential (ipsp)
-change in Vm that decreases the probability of an AP
-Erev < threshold
-usually outward K+ or inward Cl-
- may be hyperpolarizing or (rarely) depolarizing current
i.e. GABA receptor in frog spinal cord
-Vrest= -65 mV, Erev = -80 mV (only K+ flow out- hyperpolarizing), threshold = -55 mV)
-Erev < threshold -> inhibitory!
-ipsp can prevent epsp from producing an AP
Properties of Excitation and Inhibition
-whether a neurotransmitter is excitatory or inhibitory depends on the channel it opens (i.e. type of receptor)
i.e. ACh at NMJ= excitatory, ACh in parasympathetic nervous system = inhibitory
* not dependent on neurotransmitter but on receptor!*
-if average is less than threshold, AP does not occur
-take an average b/c at 2 different receptors (diff. ions)- summation occurs at same receptors
Pre-synaptic Inhibition
-inhibitory neuron terminal ends on the terminal of an excitatory neuron
- reduces amount of neurotransmitter released by excitatory neuron and can block epsp
-reduces likelihood that Ca2+ channels will open
Miniature endplate potentials (mepps)
small spontaneous depolarizations of muscle endplate
- Fatt & Katz- frog muscle experiments
-how they figured out where neurotransmitter is released
Quantal release
hypothesis that neurotransmitter is released in discrete units (bundles)
Evidence:
1. experimentally induced mepps are usually in integer values
2. increase extracellular ACh concentration at synapse -> leads to graded depolarization
- 1 molecule ACh does not = mepp
3. electron microscopy used to reveal synaptic vesicles
Neurotransmitter Release
Evidence for depolarization-release coupling:
1. Depolarizing presynaptic membrane increases frequency of mepps
2. Giant axon: increasing presynaptic depolarization increases postsynaptic depolarization
Evidence that Ca 2+ is required for neurotransmitter release:
1. When extracellular Ca2+ decreases, there was a decreased post-synaptic response
2. Depolarize to equilibirum potential of Ca2+ and there was no neurotransmitter release
3. Inject Ca2+ in presynaptic cell-> transmitter release
4. Ca2+ influx measured during depolarization
-acquorin-luminescent in presence of Ca2+
Steps in Neurotransmitter release
1. Vesicle is guided to active zone by actin- ionotropic
2. Tethered to active zone by rab protein
3. Irreversible bond formed by SNARE proteins on the vesicle and plasma membrane
4. Ca2+ binds to synaptotagmin to induce exocytosis

*This is where calcium has most important effects! (for neurotransmitter release from docked vesicles)*
Antagonists
block or counteract the effects of endogenous ligand
Agonist
Bind to the receptor to induce the same effects as the endogenous ligand. Receptors often named after their agonist
Acetylcholine
cholinergic neurons
-2 kinds of receptors: nicotinic and muscarinic
Nicotinic acetylcholine receptors (nAChR)
-Receptor Type: Ionotropic
-Location: Skeletal Muscle, autonomic, CNS
-Excitatory effect

-Studies using electroplex organ of electric rays
-nAChR can be labeled using snake venom
-5 subunits, 2 alpha-sununits
-Channel opens when both alpha-subunits bind ACh
-Desensitized channel: channel closes while ACh is still bound (if exposed to too much ACh- mini neg. feedback)
-both Na+ and K+ can go through- but Na+ is more permeable b/c of the depolarizing effect to make it excitatory
Muscarinic AChR
-ACh binds to receptor
-Receptor type: Metabotrophic
Receptor Location: smooth and cardiac muscle, endocrine glands, CNS
-excitatory or inhibitory effect
-G-protein release GDP
-G-protein binds GTP -> causes G-Protein to detach
-Activated alpha-subunit binds to K+ channel causing it to open-> inhibitory in this case
-differences in g-protein may cause activation
Amino Acid neurotransmitters
synthesized at terminal or obtained from food
-glycine, GABA, Glutamate
Glycine
Receptor: Glycine
Receptor type: ionotropic (Cl- channels)
Receptor location: CNS
Effect: Inhibitory
GABA
Receptors:
GABA-A- ionotropic (Cl- channels), located in CNS, inhibitory

GABA-B- metabotropic (K+ channels), located in the CNS, mostly inhibitory
Glutamate
Receptors:
NMDA-ionotropic (multi-ion), located in CNS, excitatory
-has regulatory binding by Mg,Zn, and glycine
-glycine required for receptor to open (cofactor)
-channel is both ligand-gated and voltage-gated: depolarization required to remove Mg blocking ion
-Membrane must be depolarized by AMPA receptor first

AMPA-ionotropic (multi-ion), located in the CNS, excitatory

mGlu (1-8)- metabotropic, located in the CNS, excitatory and inhibitory- each one has a slightly different effect

-NMDA/AMPA receptors work together- NMDA dependent on AMPA
Biogenic Amines
Synthesized from a single amino acid at axon terminals
-Dopamine, Norepinephrine, Epinephrine, Serotonin
Dopamine
Receptor= Dopamine- metabotropic, located in the CNS, excitatory or inhibitory
-catecholamine (tyrosine-derived)
Norepinephrine
Receptor= alpha and beta adrenergic- metabotropic, located in the CNS and PNS; cardiac and smooth muscle
-excitatory and inhibitory

-binds to same receptors as epinephrine but to a different extent- (doesn't bind as strongly)
-catecholaime (tyrosine-derived)
Epinephrine
Receptor= alpha and beta adrenergic- metabotropic, located in the CNS; cardiac and smooth muscle
-excitatory and inhibitory

-binds to same receptors as norepinephrine but to a different extent- (binds stronger)
-catecholaime (tyrosine-derived)
Serotonin (5-HT)
Receptor= 5-HT- metabotropic, located in the CNS, excitatory or inhibitory
-tryptophan derivative
Neuropeptides
large proteins synthesized in soma and transported to axons; more potent than small neurotransmitters
-endorphins and neuropeptide Y
Endorphins
Receptor= opiate- metabotropic, located in the CNS, mostly inhibitory
agonist=opium
Neuropeptide Y
Receptor=NPY-metabotropic, located in the CNS, excitatory
-associated w/ diet, inhibitory effect in eating
Neuromodulation
neurotransmitter release has effect on multiple nearby neurons
-mechanism of neural plasticity!
i.e. frog sympathetic ganglion
-postsynaptic cells have: nAChR (fast), mAChR (slow), and receptors for GnRH (late slow)
-the late, slow effect is modulatory: increases probability of AP (GnRH= neuromodulator)
Synaptic Integration
1. Post-synaptic current decays in dendrites; synapses closer to soma more likely to bring cell to threshold- location of synapse causes differences in response-> plasticity!
2. Spatial summation: graded potentials from multiple inputs combine
-more likely with longer t (slower repolarization) and longer lambda (signal travels farther)
-summation b/c current flowing through the same channel
Temporal summation: graded potential occuring at different times combine- more likely w/ longer t (slower repolarization) so does not degrade as fast
Synaptic Plasticity
long-lasting changes in synaptic efficiency due to experience
-i.e. short term homosynaptic modulation, heterosynaptic modulation, and long term homosynaptic modulation
Short-term homosynaptic modulation
activity in presynaptic terminal-> changes in transmitter release-> changes in postsynaptic function
-caused by facilitation, synaptic depression, and posttetanic potentiation
Facilitation
During summation (so need 2 graded potentials), the amplitude of 2nd response is greater than expected
-occurs due to residual Ca2+ (b/c Ca2+ has not all disipated)
-greater conc of Ca2+ leads to more vesicles being released and greater response
Synaptic depression
Reduction in synaptic efficiency following repeated stimulation (tetanic)
-due to depletion of vesicles
Posttetanic potentiation
After recovery from depression, the response is larger than normal- most likely due to residual Ca2+
heterosynaptic modulation
neuromodulator released from nearby axons cause changes in presynaptic function- different from neuromodulator which has post-synaptic effect
-still short term
i.e. presynaptic inhibition and heterosynaptic facilitation
heterosynaptic facilitation
amount of transmitter released is increased by neuromodulator (also pre-synaptic)
-modulators act on 2nd messengers to change conductance through pre-synaptic ion channels
long-term homosynaptic modulation
-hrs-days= long term
-type of synaptic plasticity
-can be either long-term potentiation or depression
long-term potentiation (LTP)
repetitive high frequency stimulation produces long-term increases in synaptic efficiency
-like facilitation but longer term
i.e.Mammalian hippocampus (where working memories are formed- used as an index of learning)
1. Glutamate release- rapid opening of AMPA channels and post-synaptic cell depolarizes
2. NMDA receptor opens and Ca2+ enters post-synaptic cell
3. Ca2+ leads to 2nd messenger cascade which upregulates AMPA receptors
4. Larger depolarization during subsequent stimulations- leads to larger and larger responses
long-term depression (LTD)
repetitive low frequency stimulation produces long-term decrease in synaptic efficiency
-not used enough so decrease in efficiency -> fewer and fewer receptors
Adult Neurogenesis
-example of plasticity
-growth of new neurons in the brain
-occurs in 2 neurogenic regions in the mammalian brain: hippocampus and subventricular zone
-new neurons involved in memory formation
Why study animal physiology?
1. Human Health applications
2. curiosity (within ethical standards)-> evolutionary questions
3. Animal health- pets, agricultural applications
3. commerical applications- ecosystem management and agric.-> increased productivity
Levels of organization in physiology
1. cellular and molecular physiology
2. systems physiology: how cells and tissue interact
3. organismal physiology: how intact animal performs specific processes or behavior
4. Ecological physiology: how animal physiology influences distribution and abundance of a species or population
Modes of categorization of physiology
1. biological level of organization (i.e. molecular level vs. organ systems vs. organisms)
2. nature of the process that causes physiological variation
3. ultimate goal of research
Process that generate variation
1. developmental physiology: how physiological processes change during the course of development
2. environmental physiology: how animals respond to physiological change
3. evolutionary physiology: how physiological traits arise within a lineage
Ultimate Goal
1. Applied physiology: research intended to achieve specific practical goal (i.e. exercise physiology)
2. Comparative physiology: study animals to explain the origins and nature of physiological diversity
(basic science- curiosity driven- comparing physiologys to explain different behaviors)
i.e. prairie vole (monogamous) vs. meadow vole (promiscuous) - compare brain differences
Central Themes of Physiology
1. Structure and function are interconnected-i.e. actin and myosin structure relates to function- head of myosin pulls on actin
2. Evolutionary Adaptations:
-individuals w/ well adapated physiological traits have higher probability of passing on genes
-similar physiological process in distantly related species suggests that process is adaptive for their shared environmental conditions
-i.e. both birds and animals have 4-chambered heart despite their many differences
3. Homeostatis: relatively constant internal physiological state of organisms generally maintained by negative feedback mechanism
-Conformers: allow internal condition to change w/ environmental change
-Regulators: maintain homeostasis regardless of environmental conditions-> more stable
Negative Feedback
Continuous sampling of the controlled variable couple with immediate corrective action
- controlled variable= a physiological factor that is maintained in a narrow range (i.e. glucose, pH, temp)
-set point: desired value of controlled variable- may change w/ time of day/season
-controller: integrative center that compares current value of the control variable to the set point (i.e. CNS, beta cells of pancreas)
-effector: organ or organ system that responds to bring controlled variable back to set point (i.e. liver)
-thus maintains homeostasis!
Radioisotope tracing
-trace movements of radio-labelled molecule through the body
-autoradiography to photograph location of isotopes
Immunoassays
Molecular Technique
-Antibody binds to molecule of interest
-Tissue and cellular staining
-Radioimmunoassay- competitive binding assay b/w radioactive substance vs. substance of interest
-Enzyme-linked immunosorbant assay (ELISA)- measures color change rather than radioactivity
Genetic Engineering
Molecular Technique
-Recombiant DNA: DNA from multiple sources
-Clone copies of molecules of interest
-use retrovirus to insert gene into animals- inserts genes into living cells- usually done w/ adult animals- used for gene therapy
Transgenic animals
Molecular Technique
knockouts- have no copt of gene of interest
knockdown- low levels of gene expression
-cell inserted into blastocyst (developing embryo at and early stage)
-challenge is interpreting the result- once gene is eliminated- difficult to figure out its role
DNA microarrays
Molecular Technique
-cDNA probes for entire genome or portion of genome are plated into a grid on a chip
-mRNA sample from tissue/organism is amplified and labeled with fluorescent marker
-sample mRNA hybridized with chip to determine what genes are being expressed
challenge= enormous data sets
Microelectrode
Cellular Technique
-Used to inject or measure current inside cells
-Patch clamping- allows measurements of a single ion channel
-measure ion concentrations and pressure
-fine piece of glass tubing (capillary tube)- machine heats center and pulls ends apart
Microscopy
Cellular Technique
-Fluorescent labeling
-Confocal microscopy- shines laser through tissue slide at many angles- can get a 3D image reproduced on computer
-Transmission and scanning electron microscopy- electrons shot through tissue- look at where electrons bounce off- need to use metal in sample
Cell culture
Cellular Technique
-rearing of cells in vitro
-unique culture mediums for each type of cell
-stem cells
-immortal cancer cells
Biochemical Separation Techniques
1. Spectrophotometry- sample in cuvet and laser shined through to measure transmission or reflectance to determine components
2. Chromotography
-Paper chromatography-purification technique- in general, smaller molecules will travel faster
-Column chromatography-purification technique
-High Performance liquid chromatography (HPLC)- long piece of tubing filled w/ solvent- add pressure to push product through tube
3. Electrophoresis (acrylamide, agarose)- acrylamide allows for finer scale separation than agarose (more coarse)
-separates based on charge
-southern blot: DNA
-northern blot: RNA
-western blot: protein
i.e. used for paternity analysis
Cellular Techniques
1. Microelectrodes
2. Microscopy
3. Cell culture
Molecular Techniques
1. Radioisotope tracing
2. Immunoassays
3. Genetic engineering
4. Transgenic animals
5. DNA microarrays
Ultimate vs. Proximate Causation
Proximate cause: addresses mechanisms by which a process occurs (how questions)- used generally in physiology
i.e. testosterone improves male spatial memory
Ultimate cause: evolutionary function of a physiological process (why questions)
i.e.males w/ better spatial memory acquire more mates
Species
Groups of interbreeding populations that are reproductively isolated from all other such groups
-if cannot produce viable offspring not same species
-also geographically isolated
Systematic classifications
Domain-> Kingdom-> Phylum-> Class-> Order-> Family-> Genus -> Species