Transcript synaptic transmission - UAB School of Optometry

synaptic transmission
Basic Neuroscience NBL 120 (2007)
how is the signal transferred?
electrical currents in the presynaptic process
induce currents in the postsynaptic process
 not very efficient………..
high
low
how do synapses work?
“I vividly remember visiting him
[Eccles] in his pleasant house with its
fine tennis court and beautiful view
over Sydney harbor.” (Katz, 1985)
pharmacologists versus physiologists
the lawnmower incident
chemical transmission
a synapse is both anatomically and
functionally optimized
 Ca2+
 vesicles
 postsynaptic receptors
 central synapses are just smaller than the nmj
 integration
nmj structure - anatomy overview
axon
endplate
boutons
mitochondria
vesicles
active zone
synaptic cleft
basement
membrane
junctional
fold
10,000 / m2
acetylcholine receptors
nmj - physiology overview
 stimulate motorneuron: muscle contraction
 record potential change in muscle fiber
 AP (high safety factor)
origin of the EPP
EPP: passive decay
 length constant
AP: regenerative
nmj - actetylcholine receptor
a-bungarotoxin
PORE
BINDING
SITE
GATE
Bungarus
multicinctus(pacific
(many-banded
krait)
Torpedo californica
electric ray)
acetylcholine receptor channel
single channel
EPP
closed
open
non-selective cation channel
efficiency of the EPP
v hi-fidelity synaptic transmission
v design of the perfect receptor
 high transmitter concentration in the cleft
 rapid binding to many receptors
 very fast opening (opening rate 100,000 s-1)
 99+% receptors that are bound - open
 channel closes after ≈ 1 ms
 agonist unbinds quickly (low affinity)
 degradation and diffusion
 receptor recovers without desensitization
mEPPs quantal hypothesis
smallest evoked EPP = spontaneous mEPP
Fatt and Katz (1952)
“It has been suggested that the
end-plate potential (epp) at a
single nerve-muscle junction is
built up statistically of small allor-none units [quanta or
discrete packets of transmitter]
which are identical in size with
the spontaneous ‘miniature
epp’s’” (Del Castillo & Katz, 1954)
normal EPP ≈ 200 quanta or vesicles (quantal content)
presynaptic mechanisms
object:
synchronous + fast release of many vesicles
vesicle cycling…….
 synthesis of transmitter
 storage of transmitter in
vesicles
 docking+priming of vesicles
 release (fusion) of vesicles
 action of transmitter on
postsynaptic receptors
 termination of transmitter
action
 recycling of vesicle
membrane (endocytosis)
many proteins are involved….
release…..
delay?
depolarization and Ca2+ are required
synaptic delay
Ca2+ channels open slowly…
presynaptic Ca2+ microdomains
presynaptic
terminal
 Ca2+ is only high while channels
are open
Llinas et al (1995)
Ca2+ channels / vesicles
synaptotagmin (on vesicle): Ca2+ sensor
low affinity for Ca2+
vesicles must be close to Ca2+ channels
everything is in close proximity
clearance of transmitter
 acetycholinesterase:
 10 molecules ACh per ms (one every 100 s)
 inhibition prolongs synaptic transmission…..
 diffusion is very fast
Katz and Miledi (1973)
myesthenia gravis
cholinesterase inhibitor
CNS neurons have many synapses
locations of synapses
axosomatic
(e.g. inhibition)
axodendritic
(e.g. excitation
spines)
axoaxonic
(e.g. presynaptic
inhibition)
dendrodendritic
(e.g. reciprocal
excitation)
coping with multiple synapses
how do the multiple
inputs combine to
determine the output
firing pattern of the
neuron?
dendritic
integration
and other
mechanisms
central synapses
smaller (<1 m) synaptic contact
fewer active zones:
release few vesicles
failures
don’t reach AP threshold
inhibition versus excitation
GABA
glycine
chloride
hyperpolarizing?
glutamate
ACh
serotonin
depolarizing
combining excitation and inhibition
excitatory input
excitatory input
inhibitory input
EPSP
EPSP
threshold
inhibitory
input
action potential
IPSP
no action potential
mechanism of inhibition
“Shunting inhibition”
Inhibitory transmitters (e.g. GABA) open
Cl- permeable channels. ECl is always
more negative than AP threshold. Thus,
opening up a large amount of inhibitory
channels will oppose the depolarzation
by any excitatory transmitter/receptor
and keep the membrane close to Ecl.
general rule
 relationship between:
membrane potential
ion equilibrium potentials
ENa
+67
membrane
potential (mV)
RMP
ECl
EK
-90
-98
 if the membrane becomes more permeable to one ion
over other ions then the membrane potential will move
towards the equilibrium potential for that ion (basis of AP).
temporal summation
action potentials separated in time
threshold
no postsynaptic action potential
action potentials closely spaced in time
threshold
postsynaptic action potential
spatial summation
threshold
membrane time constant
dual synaptic components…..
Wait for lecture on synaptic plasticity……
terminating the synaptic signal
just how much glutamate is around?
one role of glia at CNS synapses
transmitter
transporters
re-uptake
prevent
excitotoxicity
synaptic summary
 neuromuscular junction
 fast synaptic transmission - highly efficient
 Ca2+-dependent release of vesicles (quanta)
 postsynaptic ligand-gated ion channels
 synaptic integration in the CNS




synapse location
inhibition versus excitation
“shunting” inhibition
temporal versus spatial summation