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95 Cards in this Set
- Front
- Back
synapse
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sites of communication between all parts of neurons, glial cells, and blood vessels/muscles
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proof that synaptic transmission is not all electrical
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when Loewi added ACh to the heart muscle, he saw that it enabled the muscle to contract
(electrical activity was generated from chemical activity) |
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what causes an AP in the post-synaptic cell? (electrical)
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current flows through gap junction channels into the post-synaptic cell and depolarizes it.
If depolarization is above threshold, voltage-gated channels open and an AP is generated. |
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relationship between AP on pre-synaptic cell and post-synaptic cell in electrical synapses
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the signal on the pre-synaptic site must be much greater than the signal on the post-synaptic site because no amplification of the signal occurs (as in chemical synapses)
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characteristics of the pre-synaptic cell in electrical synapses
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1. must be large enough to contain many ion channels so a lot of current can be generated
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characteristics of the post-synaptic cell in electrical synapses
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must be relatively small because this means it will have a higher input resistance, which means it will undergo greater voltage change in response to pre-synaptic current.
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how do electrical synapses work?
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after the pre-synaptic cell is depolarized, voltage-gated channels open and current flows through them and then depolarizes the post-synaptic cell.
can be bidirectional |
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interneurons, characteristics
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1. usually inhibitory
2. important in synchronizing activity in local cells 3. use electrical transmission because it is faster and thus can preserve precise timing of signals between distant neurons |
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where are electrical synapses found?
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1. responsible for the tail flip of the goldfish
2. in interneurons |
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latency
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the amount of time between pre- and post-synaptic potentials
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advantages of electrical synapses
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1. latency is v. short
2. change in potential of post-syn. cell is directly related to size and shape of pre-syn. cell 3. any amount of current in the pre-syn. cell will produce current in the post-syn. cell. 4. most can transmit both depolarization and hyperpolarization 5. can coordinate large populations of neurons to act together 6. not very selective: anything can go through gap junction channels 7. bidirectional |
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disadvantages of electrical synapses
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1. do not provide amplification (as Ca provides in chemical synapses)
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how chemical synapses work
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1. AP at the pre-syn. terminal causes voltage-gated Ca channels in the active zone to open, Ca rushes into the cell
2. Ca causes vesicles to fuse with the pre-syn. membrane and release NT into the synaptic cleft (exocytosis) 3. NT binds to the receptors on the post-syn. cell which opens ion channels which causes depolarization of the post-synaptic cell. 4. If this depolarization is over the threshold, an AP is produced |
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structure of gap junctions
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2 hemichannnels exist: one on the pre- and one on the post-synaptic membrane
each hemichannel called a connexon connexons are made up o 6 identical protein subunits called connexins. provide low resistance |
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gap-junctions and decoupling cells
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if there is a low cytoplasmic pH or high cytoplasmic [Ca], gap junction channels close so as not to damage other cells
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ionotropic receptors
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channel and receptor are same molecule
produce relatively fast synaptic actions lasting milliseconds |
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metabotropic receptors
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channel and receptor are separate; use 2nd messengers
produce slower synaptic actions lasting seconds to minutes |
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end-plate
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where the axon of the motor neuron innervates the muscle
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synaptic bouton
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the end of a motor axon where it loses its myelin sheath and branches
it is here that the motor neuron releases its NT (always ACh) |
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neuromuscular junction
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site of communication between motor neurons and muscles
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4 features of the neuromuscular junction
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1. pre-synaptic nerve terminal
2. synaptic cleft 3. post-synaptic compartment 4. Schwann cell compartment |
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basement membrane
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50-100 nm wide
composed of collagen, laminins |
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function & location of ACh-esterases
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to degrade ACh, allowing it to leave receptors on the post-synaptic cell
anchored to the basement membrane |
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invaginations of NMJ
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contain many voltage-gated Na+ channels and ACh receptors
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proteins in the NMJ
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1. rapsyn
2. alpha-dystrobrevin 3. alpha/beta/gamma-syntrophin |
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safety factors
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90% of ACh receptors of NMJ aren't used. Presumably, there are so many because without these receptors, we would die.
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end-plate potential
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EPSP at the NMJ
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expt to study synaptic potential vs. action potential
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took extracellular voltage recordings in frog NMJ in the presence of curare (which competes with ACh and prevents a post-syn. action potential)
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2nd expt with frog NMJ
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current was recorded at distances from the stimulation and it was found that it gets less and less the farther it moves away from the point of stimulation
receptors are highly concentrated at the NMJ compared to the rest of muscle. |
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what type of experiment would you use to determine which ions move through the receptors
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patch-clamp expt
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Ach-gated channels
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generate end plate potential
allow Na+ and Ca2+ to flow in and K+ to flow out |
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rate limiting factor of the end plate current
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the time it takes to open and close ACh-gated channels
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what is a method for blocking AP in vivo?
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overexpress K+ channels in muscle fiber: too many extracellular (+) charges means no AP (because ???)_
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reversal potential of end plate ion channels
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0mV, due to the fact that the channels are equally permeable to Na+ and K+; Na+ flows in and K+ flows out.
not selective because the pore of the channel is large |
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regenerativity of voltage-gated ion channels
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increased depolarization due to Na+ influx causes more voltage-gated channels to open, which causes more depolarization, which causes more propagation of AP, which generates "all or nothing" APs.
positive feedback cycle |
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are ACh channels regnerative?
(4) |
No
the number of ACh activated channels varies according to the amount of ACh available the depolarization produced by Na+ flowing through these channels does not cause more ACh channels to open |
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what type of channel is ACh R?
(4) |
ionotropic
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structure of ACh R
(4) |
1. a membrane glycoprotein
2. formed by 5 subunits: 2 alpha, beta, theta, and epsilon |
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where does ACh bind in the ACh R?
(4) |
on the alpha subunits exposed to the membrane surface
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what happens when 2 ACh's bind to the ACh R?
(4) |
cause conformational change, opening the pore and allowing Na+ and K+ to flow through
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which subunits of ACh R are present at birth?
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2 alpha, beta, theta, and GAMMA (not epsilon)
CHECK |
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Myasthenia Gravis
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chronic autoimmune disorder that results in progressive skeletal muscle weakness
causes rapid fatigue and loss of strength eye muscles particularly affected |
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2 forms of Myasthenia Gravis
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1. congenital: caused by deficiency of ACh at the end plate
2. autoimmune: characterized by the presence of antibodies that react with ACh R --> interferes with synaptic transmission --> reduces # of ACh R --> muscles become weak |
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general function of rapsyn
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important for synapse clustering
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MuSK
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muscle-specific tyrosine kinase
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synaptic integration
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mechanism by which neurons integrate thousands of synaptic inputs to trigger an AP
input both inhibitory and excitatory |
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NMJ vs. CNS: how many innervations?
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NMJ: one muscle fiber receives input from one axon
CNS: neurons can receive input from many axons of different neurons |
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NMJ vs. CNS: does each AP trigger an AP in the post-synaptic cell?
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NMJ: yes
CNS: rarely the case because MUCH excitatory input is needed for an AP to fire (each synapse only produces about 1 mV and about 70 mV are needed) |
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NMJ vs. CNS: size of synaptic cleft
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NMJ: large
CNS: small |
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NMJ vs. CNS: types of NT
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NMJ: ACh
CNS: many--GABA, glutamate |
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NMJ vs. CNS: type of receptors
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NMJ: ionotropic
CNS: both ionotropic and metabotropic |
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NMJ vs. CNS: excitatory, inhibitory synapses
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NMJ: all synapses excitatory
CNS: both excitatory and inhibitory synapses |
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why were spinal motor neurons used to study synaptic integration?
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they're large, easily accesible, and have both inhibitory and excitatory synapses
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excitatory and inhibitory synaptic connections mediating stretch reflex
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see figure 12.1
interneuron makes excitatory connection with extensor motor neuron and an inhibitory connection with the flexor motor neuron quads are stimulated, hamstrings relaxed |
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idealized experimental setup for studying excitatory synapses
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the whole afferent nerve from the quads can be stimulated electrically with extracellular electrodes
OR single axons can be stimulated with an intracellular current-passing electrode inserted into the neuron cell body AP stimulated in the afferent neuron from quads stimulates an EPSP in the extensor motor neuron |
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idealized experimental setup for studying inhibitory synapses
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inhibitory interneurons receiving input from quad pathway are stimulated intracellularly
an AP generated in the inhibitory neuron in the extensor pathway causes an inhibitory PSP in the flexor motor neuron |
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magnitude of EPSPs in the CNS
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up to 1 mV; usually .2-.5 mV
(thus many are needed to generate an AP) |
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sculpturing
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the ability of inhibitory synapses to shape the pattern of firing in a cell
sculpturing results in a distinctive pattern of firing of impulses |
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Type I synapses
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glutamatergic (excitatory)
on dendrite wide synaptic cleft, dense pre-syn. region round synaptic vesicles |
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Type II synapses
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GABA-ergic (inhibitory)
often contact cell body narrow synaptic cleft, less obvious pre-syn. region flat synaptic vesicles |
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glutamate
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the major excitatory NT in the brain and spinal cord
mediated by both ionotropic and metabotropic receptors |
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types of ionotropic receptors (acted upon by glutamate)
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always excitatory
AMPA receptors, kainate receptors, NMDA receptors |
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metabotropic receptor (acted upon by glutamate)
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ACPD (both inhibitory and excitatory)
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APV
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drug that selectively blocks NMDA receptors
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CNQX
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drug that selectively blocks non-NMDA receptors
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early component of EPSP
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generated by non-NMDA receptors
receptors gate cation channels with relatively low conductances that are permeable to both Na+ and K+, but not Ca2+ |
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late component of EPSP
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generated by NMDA receptors
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expt that separates early component from late component (EPSP)
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voltage clamp with APV on hippocampus neurons: late component disappears when treated with APV. Thus, the early component is due to non-NMDA, late component due to NMDA (which APV blocks)
-80mV: no difference btwn APV and non-APV because NMDA is blocked by Mg2+. -40mV: small late current in non-APV +20mV: prominant late outward current in non-APV |
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how Mg2+ is expelled from NMDA receptors
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1. glutamate is released and binds to AMPA receptors
2. Na+ enters the cell via the receptors 3. this depolarization causes Mg2+ to be expelled from the NMDA receptor due to electrostatic repulsion (depolarization) |
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features of AMPA receptors
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not permeable to Ca2+, early component of EPSP, low conductance
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features of NMDA receptors
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high conductance, requires depolarization + glutamate + glycine (cofactor), permeable to Na+, K+ and Ca2+
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NMDA receptors and drugs
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PCP blocks NMDA receptors so that Ca2+ cannot enter the cell
schizophrenia is similar |
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Ca2+'s relation to NMDA receptors
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NMDA receptors let Ca2+ into the post-syn. cell, and it is responsible for carrying much of the current
Ca2+ activates other enzymes, acts as 2nd msgr. |
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GABA
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main inhibitory NT in brain and spinal cord
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expt to show how inhibitory signals work
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systematically changed the level of the resting membrane potential while stimulating an inhibitory pre-syn. neuron to fire an AP. At resting potential (-65mV), a small hyperpolarizing potential was generated when the interneuron was stimulated. At -70mV, no change in potential was recorded. At potentials more neg. than -70, a depolarizing response was discovered in the motor neuron.
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what do IPSP's result from (ion)?
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an increase in conductance to Cl- (more Cl- influx)
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axon hillock
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contains a large amount of Na+ channels with a lower threshold than soma/dendrite
the decision whether to fire an AP or not is made here |
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temporal summation
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consecutive synaptic potentials at the same site are added together in the post-syn. membrane
determined by time course of EPSP and frequency the larger the time constant, the greater the ability for temporal summation |
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spatial summation
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integration from many neurons acting on different parts of the post-synaptic membrane
depends on length constant (the larger the length constant, the more likely neurons are to be brought to threshold from 2 different inputs) |
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axo-somatic synapses
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axon to cell body
often inhibitory (sculpturing): the depolarization from an excitatory current must move through the cell body before it is propagated in the axon |
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dendro-somatic synapses
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dendrite to cell body
often inhibitory |
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axon hillock
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contains a large amount of Na+ channels with a lower threshold than soma/dendrite
the decision whether to fire an AP or not is made here |
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axo-dendritic & dendro-dendritic synapses
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often excitatory
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axo-axonic synapses
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neither inhibitory or excitatory
modulatory synapses (e.g., controls amount of NT release) |
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expt to determine if Na+ is involved in NT release
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inserted recording electrodes into the pre- and post-synaptic cells and blocked Na+ channels with TTX. AP still resulted, meaning it did not stop NT release.
when they blocked Na+ channels for 30+ minutes, they found that no AP resulted any more because the pre-synaptic potential was extinguished. |
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expt to prove K+ is not involved in NT release
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add 2 electrodes to pre-syn. cell (one recording, one stimulating) and one to the post-syn cell.
add TEA: NT release still occurs, although depolarization is constant since K+ cannot flow into the cell and repolarize it-->transmitter release is sustained |
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expt to test Ca2+ involvement in NT release
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found that if extracellular [Ca2+] is increased, there is an increase in the post-syn. potential. If extracellular [Ca2+] is decreased, there is a decrease in post-syn. potential
implied Ca2+ flows into the cell the amount of Ca2+ current through voltage-gated channels determines amount of NT release, which in turn determines magnitude of post-syn. potentials |
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abundance of Ca2+ channels at presyn. terminal
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found that there are many Ca2+ channels here, which both depolarize and act as second messengers
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Ca2+ concentration in active zone
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in the active zone during the AP, Ca2+ reaches a concentration of 100mM
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latency in EPSP
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due to the fact that it takes time for NT to bind to the post-synaptic cell.
First you see the pre-syn. AP (due to Na+ and K+), then the inward current of Ca2+, then the EPSP, then the AP in the post-syn. cell if the EPSP was above threshold |
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evoked release
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stimulated NT release; seen as multiples of the unit potential
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quantized release of NT
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produces a post-synaptic potential of fixed size
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expt to determine if NT release is quantized
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used frog NMJ and TTX
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miniature end plate potentials
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small, spontaneous post-synaptic potentials of about .5mV.
largest at site of nerve muscle contact and decay electronically with distance. frequency increased by depolarizing the pre-synaptic terminal |
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Ca2+ and quantized NT release
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alterations in external Ca2+ concentration do not affect the size of a quantum of transmitter, but the average number of quanta released in response to a pre-synaptic AP.
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