Synapses 2

Question 1

how is the CNS synapse different than the nmj in terms of mean quantal content

Answer 1

instead of a one motorneuron/nmj, there are thousands of neuronal inputs in the CNS. the mqc is 300 in motor neurons, but in the CNS it is .5.

this means in the CNS, 1 vesicle is released for every other action potential.

similarly, there are only 50 or so postsynaptic receptors. thus, the response is very small- 1 mv

Question 2

what does relatively small contributions from individual synapses mean about the CNS?

Answer 2

no one input is important- signals integrated from many different course cause change

this allows for plasticity-

Question 3

plasticity

Answer 3

the ability to change the way the brain responds to information in order to drive different behaviors. largely done through changing the efficacy of some synapses over others

Question 4

describe the localization difference between fast excitatory and inhibitory neurons in dendrites

Answer 4

excitatory- out on dendritic spines, distal from body

inhibitory- located more proximally

Question 5

3 mechanisms for terminating NT action in CNS

Answer 5

diffusion- removes NT from vicinity of receptors

reuptake- high affinity transporters expressed in presynaptic terminals and glial cells

degradation- AChE, MAO

Question 6

conserved features of ligand gated channels

Answer 6

structurally similar in that the are comprised of heterotetramers or heteropentamers

heternogenity w/in families of receptors

heterogeneity varies by function, age, sex, disease etc.

Question 7

glutamate receptors (2 types)

Answer 7

ionotropic- major excitatory in CNS

AMPA- allow Na/K
V= 0
low Ca permeability

NMDA- Na/K
high Ca permeability
V = > 0
blocked by Mg
important in long term potention and depression
important in excitatory amino acid toxicity

Question 8

how else can functional diversity be generated in receptors besides subunit heterogeneity

Answer 8

post-transcriptional editing- alternative splicing and RNA editing

Question 9

GluR2

Answer 9

a subunit in glutamate receptors, it undergoes a developmentally regulated RNA editing process where a glutamine residue is replaced with an arginine, lowering the Ca permeability

defective editing potentially linked w/ ALS

Question 10

what is the function of NMDA receptors

Answer 10

“coincidence” receptor

signal indicates when there is coordinate activity in pre and post synaptic neurons

Question 11

excitotoxicity

Answer 11

excitotoxicity w/ abnormal glutamate receptors linked to TBI, ischemia, epilepsy, ALS, MS, parkinsons, huntingtons, etc

Question 12

neuronal nicotinic AChR

Answer 12

ionotropic

Na/K (some have Ca permeability)

fast excitatory post synaptic potentials in peripheral neurons

presynaptic modulation major fxn in CNS

Question 13

GABA A receptors

Answer 13

ionotropic- inhibitory
brain
Cl and HCO3
V= -70

Question 14

glycine receptors

Answer 14

inhibitory- ionotropic
spinal cord
Cl and HCO3

Question 15

receptor subtype heterogeneity-

Answer 15

expressed in

cell specific
region specific
developmentally regulated
different parts of same cells

confers different functional and pharmcological characteristics to each receptor subtype

Question 16

allosteric GABA

Answer 16

compounds bind to GABA sites and change the channel conformation w/o acting as ligands themselves. modulation occurs in a subunit dependent way

benzos, barbiturates, anesthetics, ethanol, anabolic steroids are all capable of affecting GABA receptors

Question 17

benzos

Answer 17

in the presense of GABA, bind the a and y sites leading to increased receptor activity

results in sedation, hypnosis, and muscle relaxants

Question 18

endozepines

Answer 18

diazepam binding inhibitor

crucial role in nucleus of reticular thalamus to prevent hyperexcitability.

lack of DBI causes seizures

Question 19

extrasynaptic receptors

Answer 19

receptors outside of the synapse that are tonically activated by the low amounts of NT that exist extracellularly

for GABA, drugs like propofol and isofluorane enhance extrasynaptic receptors allosterically

Question 20

why do GABA and glycine receptors do different things during development vs in adults

Answer 20

differential expression of NKCC1 and KCC2.

young- NKCC1 predominants. transports Cl into neurons. when the receptor opens, the Cl gradient pushes it out of the cell, causing depolarization

later- KCC2 dominates, pumps Cl out of cell. when channel opens Cl rushes in, hyperpolarizing

expression can be reversed in adults following injury

Question 21

facilitation

Answer 21

increased number of vesicles released after each AP if the APs occur in rapid succession d/t residual Ca (increases the probability of release)

Question 22

synaptic depression

Answer 22

decreased number of vesicles of NT released w/ prolonged high frequency activity b/c pool of releasable vesicles is delplteed

Question 23

temporal summation

Answer 23

two events arising in rapid succession from a single input may sum w/ each other

depends on time constant

Question 24

spatial summation

Answer 24

two events arising from separate but adjacent inputs may sum w/ one another

length constant of the postsynaptic membrane

Question 25

where are nAChR found in the CNS?

Answer 25

found predominantly on presynaptic nerve terminals

have high Ca and Na permeability

depolarize and release Ca into nerve terminals

Question 26

what are the important metabotropic receptors

Answer 26

a/b norepi
serotonin
dopamine
muscarinic ACh
histamine
purinergic
metabo glutamate receptors
cannabinoid

Question 27

how do metabotropic receptors work?

Answer 27

activates G proteins causing second messenger cascade which results in amplification and divergence

amplification- one molecule can give rise to many molecules

divergence- one signaling molecule can alter activity of multiple downstream targets

Question 28

why do 5-ht receptors have extensive side effects

Answer 28

serotonin receptors are common presynaptically and affect all other major NTs

Question 29

5-ht and alzheimers

Answer 29

5-ht2a receptors promote excitation of cotical neurons, and decline in parrallel to cognitive function in alzheimers

Question 30

describe the CB/DA relationship in the NA and VTA

Answer 30

DA neurons run from the VTA to the NA, there they release DA. presynaptically, they are innervated by GABA neurons, which inhibit them. these GABA neurons have CB on them, which decrease cAMP, which makes it harder to open Ca channels, meaning GABA is less likely to be released

GABA is inhibitory. when it is less likely to be released, it makes it less likely that the DA neuron will be inhibited

Question 31

ratio of neurons to glia

Answer 31

1:1

Question 32

functions of glia

Answer 32

regulate [k]

take up NTs

myelination

neuronal migration

respond to unjury

generate Ca waves that spread and cause release of substances

Question 33

oligodendrocytes

Answer 33

myelinating glia

Question 34

astrocytes

Answer 34

mediators of ion and metabolic homeostasis. most common glia cell

control numbers and functoins of synapses

regulate bloodflow

synaptic pruning (complement_

Question 35

thrombospondins and cholesterol

Answer 35

substances released from astrocytes that promote morphological synaptogenesis

Question 36

NG2

Answer 36

act as synaptic partners and are important in synaptic remodleing

drastically increased after injury, play a role in repair and regeneration

Question 37

microglia

Answer 37

phagocytosis and defense

Question 38

schizophrenia theory

Answer 38

in normal conditions, synapse elimination occurs in early adult hood, which is when symptoms are first manifested

in schizos, abnormally high C4 complement found, indicating high microglial synapse elimination

Question 39

gap junctions

Answer 39

channel called connexon, formed by connexin. allow current to flow directly and common in developing neurons

Question 40

gap junction disease

Answer 40

account for significant portion of non syndromic deafness