Cell Neuro Exam 2 -

- Synaptic Transmission

What are the two classes of postsynaptic receptors?

1. Ionotropic - direct transmitter action

2. Metabotropic - indirect transmitter action

What are ionotropic receptors and give examples

ligand gated ion channels - allows ions to flow across membrane directly

nAChR, AMPAR, NMDAR

What are metatropic receptors

indirectly activates an ion channel through a cascade (through secondary messenger). they are not channels themselves.

where are ionotropic and metatropic neurons found?

postsynaptic terminal membrane

What is the neuromuscular junction (NMJ)

synapse where motor neuron meets skeletal muscle fiber

What happens at the junction in terms of neurotransmitters

acetylcholine is released at the motor neuron and binds to nAChR which excites the muscle.

what is the forward reaction of Acetylcholine (ACh) and what is the enzyme ivolved

Acetyl-CoA + Choline —> ACh

enzyme: ChAT

what is the reverse reaction for ACh and enzyme involved

Ach —> Acetyl Coa+Choline

enzyme: AChE

What Dale’s Law

A neuron only releases one type of neurotransmitter

How are neurons activity influenced by

many different inputsD

Does a neurotransmitter have the same effect on every post-synaptic neuron?

no —> determined by the type of postsynaptic receptor

How does nAChR work like molecularly to produce an excitatory contraction of the muscle

1. Ach binds to nAChR allowing it to ope

2. muscle membrane is usually negative and there is an inflow of K+ (depolarization) and flow out of Na+

3. Moves the membrane towards reversal potential of ~0mV causing muscle contraction

What happens to ACh after it is used to create contraction

on the synapse, ACh is broken down by AChE (acetylcholinesterase) and then the choline is transported back into the presynaptic neuron to create more ACh

How are synaptic activity quantified by?

recordings from the post synaptic membrane either an EPSP or EPSC

what is EPSP

• EPSP (Excitatory Postsynaptic Potential): Measures the change in voltage across the membrane.

• 
  

What is EPSC

• EPSC (Excitatory Postsynaptic Current): Measures the actual flow of ions (current).

• 
  

what is curare

competative antagonist of nAChR

• blocks Ach from binding

what is sarin nerve gas

Acetylcholinesterase inhibitor (AChE)

• blocks the breakodwn of ACh

What is competitive antagonist

binds to same site as agonist and blocks site from being activated

What is noncompetitve antagonist

binds to an allosteric (non-agonist) site ont he receptro to prevent activation of receptor

What does vesicle release depend on?

It is probabilistic and depends on Ca2+ levels —> more Ca —> more prob of release.

are there infinite vesicles?

no finate amt in releasable pool

Go through the steps of how vesicle release at the presynaptic neuron works (5)

1. Action potential moves down the presynaptic neuron

2. depolarization opens Ca2+ channels

3. causes Ca2+ to flow in a localized domain (in presynaptic neuron)

4. Ca2+ binds to synaptotagmin causing opening of fusion pore

glutamate flows out and binds to AMPAR —> AMPAR opens

How do vesicles dock to new membrane? (2)

1. V-SNAREs on the vesicle and T-SNAREs on pre-synaptic membrane wind together (coil-coil complex) to pull vesicle towards membrane (getting ready to release)

2. Munc-18 holds to SNARE proteins together

3. the incoming Ca binds to the Ca domains on the Synaptotagmin and is the last riger to release neurotransmitters into synapse

what does tetnaus and botox do

destroys SNAREs which blocks neurotransmitters from being bound and moved into post-synaptic neuron

what does botox specifially target/block

target NMJ and ACh

what is a sEPSP

spontaneous excitatory post synaptic potential —> MEASURES VOLTAGE of the POSTSYNAPTIC neuron once it recieves NT signal

• spontaneous release of neurotransmitter vesicles that dont require an AP

what is the quantal hypothesis

quantal events are caused by the release of a single vesicle (quanta) of the NT

How is quantal analysis done?

reduce extracellular Ca2+ concentration so APs dont cause depolarization which would release a ton of NT (vesicle fusion)

What is mESPS

mini EPSP which is a type of sEPSP but it is the post-synaptic potential (voltage) following the release of a single vesicle

what is quantal size

amplitude of the post synaptic response (mV) in response to a single vesicle release (measures mEPSP)

what is quantal content

Average # of vesicles that are released following a single AP or stimultion

match presynaptic property and post synaptic property to quantal content or size

presynaptic property - quantal content

postsynaptic property - quantal size

how does phosphorylation impact quantal content

phosphorylation of Ca2+ channels leave them open for longer —> more vesicle release

how is quantal content (m) calculated with n and p

n (number of release sites) p (probability of release)

n * p = m

how is quantal size calculated/found?

its the mV that is generated by a single veiscle. look at peak of the first vesicle and see what mV it is at

How is EPSP amplitude calculated and what is it

EPSP amplitude - total post-synaptic potential change following an action potential (multiple vesicle releases)

EPSP amplitude (mV) = q*m

• OR q*n*p

q = in mV and measures the potential change caused by one veiscle (quantal size)

m = average number of vesicles released following a single AP (quantal content)

what is q, m, n, p

q - quantal size, size of post synaptic potential following single vesicle release (mV) (basically mEPSP)

m - quantal content, average number of presynaptic vesicles released

n - number of vesicle release sites on membrane after single AP/stimulation

p - probability of vesicle release

how is q related to mEPSP

amplitude of mEPSP = q

what are the two ways that EPSP amplitude can increase

1. increase in m (quantal content and av number of vesicle release)

2. increase in q (quantal size and the actual impact in mV of each vesicle release)

What does an EPSP amplitude of 0mV mean? what does each peak represent?

• 0 mv - means that there was a failure to release any vesicles

• each peak represents a the increase in one more vesicle release (peak 1 represents no veiscle peak 2 means 1 vesicle, ect)

what does a weak synapse mean (3) aka what are the factors that can make a synapse weak?

1. lower release probability (p)

2. lower number of release sites (n)

3. lower quantal size (q)

What is a paired pulse experiment

Delivering two back-to-back stimulations (AP) to cause two EPSPs and measure them

how does paired-pulse reveal high or low release probability

for low probability —> second EPSP amplitude is greater because the first EPSP releases very little vesicles and there is a lot of leftover Ca2+ on the membrane which causes more vesicle release on the second EPSP causing a higher amplitude

for high probability —> second EPSP is weaker because first EPSP release a lot of vesicles and there isnt enough time to replenish for the second EPSP

what is short term depression? and what kind of release probability does it correspond to

depletion of readily releasable vesicle pool, explains initial high release probability

what is short term facilitation? and what kind of release probability does it correspond to

short-term facilitation: residual Ca2+ increases probability of release to second pulse

corresponds to initial low release probability

how do u find ppr

amplitude of EPSP2/amplitude of EPSP1

What does it mean if paired pulse ratio (PPR) is less than 1

indicates that EPSP2<EPSP1 so short term depression

what does PPR > 1 mean

EPSP2>EPSP1 so short term facilitation

What does botox and tetanus do to NMJ

destroy SNARE proteins which means that there is no ACh vesicle fusion and release —> paralysis of muscles (weakness)

what does a-Latrotoxin do

makes pores in the membrane for easier Ca2+ entry —> more Ach release —> more rigidity

what is myasthenia gravis (MG) and what does it attack

attacks the post synaptic AChR which means that ACh cant bind causing musle weakness

how is MG treated

treat by blocking AChE

what is lambert-eaton syndrome (LEMS)

attacks the presynaptic mechanism of voltage gated Ca2+ channels which causes no release of ACh and muscle weakness

What does curare do

blocks AChR so no inflow of Na+ at the post-synaptic neuron which means no depolarization and AP so no muscle contractions

what does a-BGt do

blocks AChR so no inflow of Na+ at the post-synaptic neuron which means no depolarization and AP so no muscle contractions

what does sarin nerve gas do?

blocks AChE so no degredation of ACh —> increased firing of muscle nueons and lots of muscle contractions

What is AMPA and what kind of IV plot does it create

linear IV plot

opens quickly when Glu binds and lets Na+ in K+ out (ionotrophic)

What are the antagonists of AMPA (3)

CNQX, DNQX, NBQX

What is NMDA and what kin d of IV plot does it produce

exponential IV plot

Glutamate and Glycine need to bind + depolarization to allow Mg plug to leave —> channel opens Na, Ca rush in K out

What are the antagonists for NMDA? (2)

APV, MK801

How do the kinetics of NMDAR compare to that of AMAPR

NMDAR is slower

Practice go

AT - 70MV NMDAR is blocked (cell needs to be depolarized to remov Mg+ ion block). So using APV to block NMDAAR wont do anything but using CNQX to block AMPA will

Practice gooooo

Vhold is less negative so smaller force that drives Na inwards is smaller. Blocking NMDAR (using APV) shows the fast spike of the AMPAR and blocing AMAPR (using CNQX) shows the smaller and slower spike of the NMDAR

practice gogogogogo

Vhold = +70mV means realllyyyy deplarized so bye bye Mg+ block!

blocking NMDAR (APV) shows peak from just the AMAPR (sharp and fast)

blocking AMAPR (CNQX) shows peak from just NMDAR (slower and weaker)