Synaptic Transmission and Receptors

Question 1

how are vesicles connected and what enables their release?

Answer 1

vesicles are bound one another by synapsin, action potentials cause voltage-gated calcium channels to open, calcium influx activates CaMKII enzymes, CaMKII (kinase) then phosphorylates synapsin and allows vesicles to be released from the reserve pool

Question 2

what are the steps of vesicle exocytosis?

Answer 2

docking, priming, fusion and release

Question 3

how does vesicle docking in the active zone work?

Answer 3

vesicles get stuck to the docking site and are held together by protein tethers (mast, boom, spar, rib, and pin) of the active zone, scaffolding also contains voltage-gated Ca2+ channels, they combine into a releasable pool

Question 4

what primes vesicles in the active zone for fusion?

Answer 4

v-SNAREs (synaptobrevin) bind with t-SNAREs (syntaxin and SNAP-25) and with Munc-18 (active zone protein), moves vesicles in contact with the cell membrane to ready them for release

Question 5

what is the reserve pool vs the releasable pool?

Answer 5

reserve pool is a group of vesicles bound together within the cell while the releasable pool is a group of vesicles bound to the membrane

Question 6

how does vesicle release occur after the SNARE complex forms?

Answer 6

synaptotagmin binds to the SNARE complex, incoming action potentials cause voltage-gated calcium channels to open allowing Ca2+ to bind to the synaptotagmin which curves the membrane and creates enough pressure to fuse the vesicle with the cell membrane, this allows for AP dependent (Ca2+ regulated) exocytosis

Question 7

what is quantal release?

Answer 7

the release of as much neurotransmitter as would be released by a single vesicle, one quantum = 1 vesicle, local potentials are determine by a small number of quantums

Question 8

what does low probability release mean?

Answer 8

as the number of active zones increases so does the chance of an action potential occurring

Question 9

how does dense core vesicle release differ from clear core vesicle release?

Answer 9

they have a reserve pool further from the active zone which requires multiple action potentials and calcium for active zone entry, docking occurs with the same protein tethers

Question 10

how do exosomes release?

Answer 10

small vesicles form early endosomes, which then turn into late endosomes when they form vesicles within them, form multivesicular bodies when they absorb multiple vesicles, then regulated presynpatic receptor stimulation triggers calcium dependent exocytosis from multi vesicular bodies in vesicles that leave cell

Question 11

what are the four types of membrane recapture?

Answer 11

kiss-and-stay: vesicles can refill with NT even after release
kiss-and-leave: releases contents and leaves the membrane but stays nearby to refill
endosomal membrane retrieval: endocytosis forms early and then late endosomes due to membrane infolding
bulk retrieval: multiple vesicles release in bulk at once

Question 12

what do trans-synaptic adhesion molecules do?

Answer 12

they span the membrane to hold the synapse together and line up active sites with one another

Question 13

what do neurexins do?

Answer 13

they are presynaptic adhesion molecules that connect the active zone protein complex to the postsynaptic adhesion molecules

Question 14

what do neuroligins do?

Answer 14

connected to the postsynaptic density protein complex and PSD95 that clusters glutamate receptors, holds excitatory proteins in place to increase glutamatergic synaptic efficacy

Question 15

how are GABA A receptors connected to the membrane?

Answer 15

connect to the scaffolding protein gephyrin instead of PSD95, holds inhibitory proteins in place to increase gabaergic synaptic efficacy

Question 16

what does PSD95 do to NMDAR vs AMPAR?

Answer 16

PSD95 attaches to NMDAR directly to hold them in place while PSD95 attaches to TARP proteins that then attach to AMPAR to travel up and down the membrane by using PSD95 as a train track

Question 17

what does catenin do?

Answer 17

alpha and beta catenin form a calcium dependent bond that keeps the synapse together, lack of Ca2+ (indicating an inactive synapse) causes them to let go of each other and release the synapse

Question 18

what does the postsynaptic density contain?

Answer 18

receptors, ion channels, scaffolding proteins (PSD95, gephyrin), actin cytoskeleton, and enzymes/signaling molecules

Question 19

how are postsynaptic receptors dynamically regulated?

Answer 19

PSD95 moves NMDA into the center and AMPA further out, TARP and gephyrin move receptors laterally, CaMKII phosphorylates specific sites on the receptor in order to either retract or insert receptors into the membrane

Question 20

what is the extracellular matrix made of?

Answer 20

interstitial extracellular matrix and perineuronal nets

Question 21

what is in the interstitial extracellular matrix?

Answer 21

makes up 20% of brain volume, contains proteoglycans and hyaluronic acid which binds to water to maintaining water level within the cell

Question 22

what are perineuronal nets made of and what do they do?

Answer 22

made up of sugar and proteins, located 70% on PV interneurons in the cortex and 30% on pyramidal neurons, involved in learning and memory by locking things in place, break down at night to allow memories to be updated before they are resolidified

Question 23

what does the tripartite/quadripartite synapse do?

Answer 23

astrocytes and pre-synaptic terminals take up K+, glutamate, and GABA that accumulates after AP, post-synaptic terminal can also assist since glutamate is toxic in high volumes, astrocytes have receptors that can respond to NT, astrocytes and microglia can release gliotransmitters to alter pre/post-synaptic activity

Question 24

what are the differences between electrical and chemical synapses?

Answer 24

electrical synapses are much closer together and less selective, voltage-gated or signal-gated, can be between glial cells too, faster than chemical synapses so they allow for synchronized activity between cells

Question 25

how do clear coat vesicles, dense core vesicles, and exosomes differ?

Answer 25

clear coat vesicles contain precursors for NT (already at active zone), dense core vesicles contain neuropeptides (take longer to get to active zone so sustained activity it required to release them), exosomes carry enzymes, microRNA, lipids (received through endocytosis into endosomes which release them in response to calcium, can exocytosis on their own so they travel around until they bind to a cell they want to release into)