Download Chemical Synapses

M555 Medical Neuroscience
Synapses
Introduction
communication is the central task of the nervous system
there are sites (and plenty of them) where nerve cells communicate
with other nerve cells .... and with sensory cells, muscle cells and gland cells
points of communication - synapses
at synapse, a change in the membrane potential
of one cell may produce a change in the membrane potential of another cell
Electrical Synapses
(Electrotonic Synapses)
structure: opposed plasma membranes of cells at an E synapses
are in near contact
proteins acting like membrane-spanning pores align in adjacent cells
from figure 8-25
passage through gap junction pores
direction of electric current
gap junction proteins
found in human CNS
excitatory neurons in the retina, inferior olive, thalamus, hippocampus, olfactory bulbs
inhibitory neurons in cerebral cortex
functional characteristics
cell-to-cell transmission
if one neuron depolarizes,
the other neuron ...
looking at a larger picture
rapid synaptic communication
synchronization of activity
if one neuron hyperpolarizes,
the other neuron ...
electrical synapses-like structures
are present in some glial cells
a role in helping astrocytes
regulate extracellular [K+] and modify interneuronal signalling
a role in intracellular transport within Schwann cells
from figure 8-26
malfunction of connexin proteins in Schwann cells
group of disorders
inherited peripheral neuropathy
Chemical Synapses
“chemical” due to the involvement of chemical molecules to
carry a signal from one cell to the next
relevance
Chemical Synapses
two major classes
channel-linked chemical synapses
basic structure
K+
K+
G protein-linked chemical synapses
basic structure
Na+
Ca++
Na+
K+
K+
Ca++
Na+
Na+
Ca++
Ca++
nucleus
K+
nucleusK+
1) Axon Terminal of Presynaptic Neuron
2) Ca++ Channels in Plasma Membrane
of AxonTerminal
3) Synaptic Cleft
1) Axon Terminal of Presynaptic Neuron
4) Postsynaptic Neuron
4) Postsynaptic Neuron
5) Neurotransmitter Vesicles in Axon Terminal
5) Neurotransmitter Vesicles in Axon Terminal
6) Receptors for Neurotransmitter
and Ion Channels
(together in same structure)
6) Receptors for Neurotransmitter
2) Ca++ Channels in Plasma Membrane
of AxonTerminal
3) Synaptic Cleft
7) Ion Channels
8) G proteins
variations in chemical synapses
axon
axon
axon
axon
“boutons en passage”
one way to modulate
synaptic effect
axon
postsynaptic cell
Chemical Synapses
basic function
> AP in presynaptic neuron
how they function in general: > depolarization of axon terminal
> entrance of calcium ions into axon terminal
> exocytosis of neurotransmitter
> diffusion of neurotransmitter across synaptic cleft
> binding of neurotransmitter to receptor molecules of postsynaptic cell
> initiates response in postsynaptic cell
hyperpolarization = inhibitory
depolarization = excitatory
> removal of released neurotransmitter
some more details for channel-linked chemical synapses
First Step - Presynaptic neuron fires action potentials which travel toward axon terminal
depolarization of terminal opens
action potentials
action potentials
Ca++ channels in axon terminal;
depolarize axon terminal
reach axon terminal
Ca++ diffuses into axon terminal
AP
Ca++
K+
after entrance of Ca++;
neurotransmitter vesicles
dock with plasma membrane
K+
neurotransmitter vesicles
fuse with plasma membrane;
exocytosis of neurotransmitter
K+
K+
neurotransmitter molecules
bind with receptors
on postsynaptic cell
K+
receptors binding
neurotransmitters
become activated
K+
neurotransmitter molecules
diffuse across
synaptic cleft
K+
activated receptors
lead to opening (or closing)
of ion channels
K+
K+
Last Step - Membrane potential of postsynaptic neuron depolarizes (or hyperpolarizes)
Chemical Synapses
basic function
> AP in presynaptic neuron
how they function in general: > depolarization of axon terminal
> entrance of calcium ions into axon terminal
> exocytosis of neurotransmitter
> diffusion of neurotransmitter across synaptic cleft
> binding of neurotransmitter to receptor molecules of postsynaptic cell
> initiates response in postsynaptic cell
hyperpolarization = inhibitory
depolarization = excitatory
> removal of released neurotransmitter
some more details for channel-linked chemical synapses
First Step - Presynaptic neuron fires action potentials which travel toward axon terminal
depolarization of terminal opens
action potentials
action potentials
Ca++ channels in axon terminal;
depolarize axon terminal
reach axon terminal
Ca++ diffuses into axon terminal
AP
Ca++
K+
after entrance of Ca++;
neurotransmitter vesicles
dock with plasma membrane
K+
neurotransmitter vesicles
fuse with plasma membrane;
exocytosis of neurotransmitter
K+
K+
neurotransmitter molecules
bind with receptors
on postsynaptic cell
K+
receptors binding
neurotransmitters
become activated
K+
neurotransmitter molecules
diffuse across
synaptic cleft
K+
activated receptors
lead to opening (or closing)
of ion channels
K+
K+
Last Step - Membrane potential of postsynaptic neuron depolarizes (or hyperpolarizes)
Chemical Synapses
fusion of vesicles with plasma membrane of axon terminal
neurotransmitter in vesicle
docking
proteins
axon
terminal
synaptic cleft
receptors
postsynaptic membrane
neurotransmitter vesicles
lighter
and smaller diameter
dense cores
and larger diameter
axon terminals
cleft
postsynaptic membrane
cleft
postsynaptic membrane
Chemical Synapses
Neurotransmitters
molecular messengers used at chemical synapses
why are chemical messengers needed at chemical synapses?
AP
axon
postsynaptic
cell
classes of neurotransmitters
acetylcholine (ACh)
in PNS
neuromuscular junction receptors:
H
O
HCH
H
preganglionic autonomic receptors:
H
+ CH
H
C
H C
N H
postganglionic parasympathetic receptors:
O
C
C
H
HH
H HCH
H
in CNS
brain stem and basal forebrain receptors
cathecholamines (monoamines, biogenic amines)
tyrosine
tryptophan
COOH
tryptophan hydroxylase
CH2 CH NH2
HO
tyrosine
hydroxylase
5-hydroxytryptophan
decarboxylase
DOPA dihydoxyphenylalanine
HO
COOH
CH2 CH NH2
N
H
HO
OH
CH2 CH2
norepinephrine
dopamine
OH
beta-hydroxylase
NH2
CH CH2 NH2
HO
OH
serotonin
dopa
decarboxylase
dopamine
HO
CH2 CH2 NH2
PNMT
epinephrine
OH
CH CH2 NH
CH3
HO
OH
OH
figures 8-20 and 8-21
Chemical Synapses
Neurotransmitters
amino acids
glutamate and aspartate
glutamate receptors
most are channel-linked
special type: NMDA receptor
(“NMDA” = N-methyl-D--aspartate)
Na+
Na+
glutamate
glutamate
glutamate
interstitial
Ca++
glutamate
interstitial
intracellular
Mg++
intracellular
NMDA
glutamate
receptor
coventional
glutamate
receptor
coventional
glutamate
receptor
small depolarization of
neuron’s membrane potential
NMDA
glutamate
receptor
larger depolarization of
neuron’s membrane potential
lasting change in synapse
long-term potentiation
possible excitotoxicity
amino acids
COOH
glutamate
CH2
CH2
H2N
C
GABA (gamma amino butryic acid)
peptides
substance P
endogenous opioids
CH2
H
COOH
nitric oxide
COOH
glutamic acid
decarboxylase
CH2
H 2N
and glycine
CH2
GABA
Chemical Synapses
fate of neurotransmitters
inactivation
reuptake
uptake
diffusion
figure 8-7
interaction of NT and receptors
Chemical Synapses
changes in membrane potential of postsynaptic cell
excitatory postsynaptic potential
regarded as excitatory ...
membrane potential
electrode
*
active
excitatory
synapse
initial
segment
axon
inhibitory postsynaptic potential
regarded as inhibitory ...
membrane potential
electrode
active
inhibitory
synapse
*
initial
segment
axon
commonly, a combination of excitatory and inhibitory chemical synapses
decisions
decisions
decisions
do
something!!
do
this!
do
that!
do
nothing!!
what do I do?
is he going to tell us
to do something?
postsynaptic potentials
figure 8-3
or not?
Chemical Synapses
summation of synaptic potentials recorded at initial segment
1
2
temporal and
spatial summation -
1+ 2
synaptic potentials
occurring at same time
at different sites
2+ 3
note:
3
2
3
1
from figure 7-9
postsynaptic cells
why focus on membrane potential of the axon’s initial segment?
a much simplified example
of neuronal integration