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Transcript
Synaptic Transmission
1
Synaptic contacts
Axodendritic – axon to
dendrite
 Axosomatic – axon to
soma
 Dendrodendritic – capable
of transmission in either
direction
 Axoaxonal – may be
involved in presynaptic
inhibition

2
Structure of the Synapse
microtubules
Synaptic
vesicles
Button
Synaptic cleft
Golgi complex
Mitochondrion
Dendritic
spine
Presynaptic membrane
Postsynaptic membrane
3
Release of Neurotransmitter
Exocytosis – the process of neurotransmitter
release
 The arrival of an AP at the terminal opens
voltage-activated Ca++ channels.
 The entry of Ca++ causes vesicles to fuse with
the terminal membrane and release their
contents


http://www.tvdsb.on.ca/westmin/science/sbioac/homeo/synapse.htm
4
Exocytosis
Terminal Button
Ca+
Ca+
5
Neurotransmitter Molecules

Two basic categories:
– Small molecule
 Synthesized in the terminal button and packaged
in synaptic vesicles.
– Large molecule (peptide)
 Assembled in the cell body on ribosomes,
packaged in vesicles, and then transported to the
axon terminal.
6
Types of Synapses
Directed – the site of neurotransmitter
release and receptor activation are in
close proximity.
 Nondirected – the site of release is at
some distance from the site of reception.

7
Presynaptic activation of
ACh muscarinic receptors
suppresses synaptic
transmission at intrinsic
fiber synapses but not at
afferent fiber synapses.
Postsynaptic activation
suppresses normal
adaptation of pyramidal
cell firing by blocking
voltage- and Ca+dependent K+ currents.
Combined, these effects
may prevent recall of
previous memory from
interfering with the
learning of new
memories.
(Adapted from Hasselmo, 1995)
8
Receptor-neurotransmitter
interactions
Released neurotransmitter produces signals in
postsynaptic neurons by binding to receptors.
 Receptors are specific for a given
neurotransmitter.
 Ligand – a molecule that binds to another.
 A neurotransmitter is a ligand of its receptor.

9
Receptors
There are multiple receptor subtypes for
each neurotransmitter molecule.
Two general classes of receptors:
1. Ionotropic receptors – associated with
ligand-activated ion channels.
2. Metabotropic receptors – associated with
signal proteins and G proteins
1. Postsynaptic
2. Presynaptic (autoreceptors)
10
11
Deactivating Neurotransmitters
As long as neurotransmitter is in the
synapse, it is active – activity must
somehow be turned off.
1. Reuptake – neurotransmitter is
taken back into the presynaptic
terminal.
2. Enzymatic degradation –
neurotransmitter is broken down by
enzymes.
12
Small-molecule Neurotransmitters
Amino acids – the building blocks of
proteins
 Monoamines – all synthesized from a
single amino acid
 Soluble gases
 Acetylcholine (ACh) – activity terminated
by enzymatic degradation

13
Amino Acid Neurotransmitters
Usually found at fast-acting directed
synapses in the CNS
 Glutamate – Most prevalent excitatory
neurotransmitter in the CNS
 GABA –
– synthesized from glutamate
– Most prevalent inhibitory
neurotransmitter in the CNS
 Aspartate and glycine

14
Monoamines
Effects tend to be diffuse
 Catecholamines – synthesized from
tyrosine
– Dopamine
– Norepinephrine
– Epinephrine
 Indolamines – synthesized from
tryptophan
– Serotonin (5-HT).

15
Acetylcholine and soluble gases

Acetylcholine (Ach)
– Acetyl group + choline
– Neuromuscular junction

Soluble gases – exist only briefly
– Nitric oxide and carbon monoxide
– Retrograde transmission – backwards
communication
16
NMDA Receptor Activation
Na+
Glutamate
Ca2+
Polyamine
Glycine /
D-Serine
Zn2+
PCP
Mg2+
PSD-95
NO *
Ca2+
CaM
L-Citruline
NOS
L-Arginine
17
D-serine localization in rat brain
18
What is the NMDAR System and
How Does it Function?
NMDA is a receptor for one of
the most prominent excitatory
neurotransmitters in the brain
(Glutamate)
 NMDA Receptors require coactivation of 2 ligands
(Glutamate and Glycine)
 Ion channel opens allowing Na+
and Ca+ in and K+ out

NMDA Receptor Distribution
Striatum
Hippocampus
Pharmacology of Synaptic
Transmission
Many drugs act to alter neurotransmitter
activity
 Agonists – increase or facilitate activity
 Antagonists – decrease or inhibit activity
 A drug may act to alter neurotransmitter
activity at any point in its “life cycle”
21
22
Examples of Agonists

Cocaine - catecholamine agonist
– Blocks reuptake – preventing the activity of
the neurotransmitter from being “turned off”

Benzodiazepines - GABA agonists
– Binds to the GABA molecule and increases
the binding of GABA
23
24
Examples of Antagonists
Atropine – ACh antagonist
– Binds and blocks muscarinic receptors
– Many of these metabotropic receptors
are in the brain
– High doses disrupt memory
 Curare - ACh antagonist
– Bind and blocks nicotinic receptors, the
ionotropic receptors at the
neuromuscular junction
– Causes paralysis

25
26