Synapses 2 Flashcards
how is the CNS synapse different than the nmj in terms of mean quantal content
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
what does relatively small contributions from individual synapses mean about the CNS?
no one input is important- signals integrated from many different course cause change
this allows for plasticity-
plasticity
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
describe the localization difference between fast excitatory and inhibitory neurons in dendrites
excitatory- out on dendritic spines, distal from body
inhibitory- located more proximally
3 mechanisms for terminating NT action in CNS
diffusion- removes NT from vicinity of receptors
reuptake- high affinity transporters expressed in presynaptic terminals and glial cells
degradation- AChE, MAO
conserved features of ligand gated channels
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.
glutamate receptors (2 types)
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
how else can functional diversity be generated in receptors besides subunit heterogeneity
post-transcriptional editing- alternative splicing and RNA editing
GluR2
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
what is the function of NMDA receptors
“coincidence” receptor
signal indicates when there is coordinate activity in pre and post synaptic neurons
excitotoxicity
excitotoxicity w/ abnormal glutamate receptors linked to TBI, ischemia, epilepsy, ALS, MS, parkinsons, huntingtons, etc
neuronal nicotinic AChR
ionotropic
Na/K (some have Ca permeability)
fast excitatory post synaptic potentials in peripheral neurons
presynaptic modulation major fxn in CNS
GABA A receptors
ionotropic- inhibitory
brain
Cl and HCO3
V= -70
glycine receptors
inhibitory- ionotropic
spinal cord
Cl and HCO3
receptor subtype heterogeneity-
expressed in
cell specific
region specific
developmentally regulated
different parts of same cells
confers different functional and pharmcological characteristics to each receptor subtype
allosteric GABA
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
benzos
in the presense of GABA, bind the a and y sites leading to increased receptor activity
results in sedation, hypnosis, and muscle relaxants
endozepines
diazepam binding inhibitor
crucial role in nucleus of reticular thalamus to prevent hyperexcitability.
lack of DBI causes seizures
extrasynaptic receptors
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
why do GABA and glycine receptors do different things during development vs in adults
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
facilitation
increased number of vesicles released after each AP if the APs occur in rapid succession d/t residual Ca (increases the probability of release)
synaptic depression
decreased number of vesicles of NT released w/ prolonged high frequency activity b/c pool of releasable vesicles is delplteed
temporal summation
two events arising in rapid succession from a single input may sum w/ each other
depends on time constant
spatial summation
two events arising from separate but adjacent inputs may sum w/ one another
length constant of the postsynaptic membrane
where are nAChR found in the CNS?
found predominantly on presynaptic nerve terminals
have high Ca and Na permeability
depolarize and release Ca into nerve terminals
what are the important metabotropic receptors
a/b norepi serotonin dopamine muscarinic ACh histamine purinergic metabo glutamate receptors cannabinoid
how do metabotropic receptors work?
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
why do 5-ht receptors have extensive side effects
serotonin receptors are common presynaptically and affect all other major NTs
5-ht and alzheimers
5-ht2a receptors promote excitation of cotical neurons, and decline in parrallel to cognitive function in alzheimers
describe the CB/DA relationship in the NA and VTA
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
ratio of neurons to glia
1:1
functions of glia
regulate [k]
take up NTs
myelination
neuronal migration
respond to unjury
generate Ca waves that spread and cause release of substances
oligodendrocytes
myelinating glia
astrocytes
mediators of ion and metabolic homeostasis. most common glia cell
control numbers and functoins of synapses
regulate bloodflow
synaptic pruning (complement_
thrombospondins and cholesterol
substances released from astrocytes that promote morphological synaptogenesis
NG2
act as synaptic partners and are important in synaptic remodleing
drastically increased after injury, play a role in repair and regeneration
microglia
phagocytosis and defense
schizophrenia theory
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
gap junctions
channel called connexon, formed by connexin. allow current to flow directly and common in developing neurons
gap junction disease
account for significant portion of non syndromic deafness
