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Axodendritic – axon to dendrite
Axosomatic – axon to soma
Dendrodendritic – capable of transmission in either direction
Axoaxonal – may be involved in presynaptic inhibition
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microtubules
Synaptic vesicles
Button
Synaptic cleft
Golgi complex
Mitochondrion
Dendritic spine
Presynaptic membrane Postsynaptic membrane
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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
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Ca+
Exocytosis
Terminal Button
Ca+
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Neurotransmitter Molecules
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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.
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Directed – the site of neurotransmitter release and receptor activation are in close proximity.
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Nondirected – the site of release is at some distance from the site of reception.
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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)
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Receptor-neurotransmitter interactions
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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.
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There are multiple receptor subtypes for each neurotransmitter molecule.
Two general classes of receptors:
1.
2.
Ionotropic receptors – associated with ligand-activated ion channels.
Metabotropic receptors – associated with signal proteins and G proteins
1.
Postsynaptic
2.
Presynaptic (autoreceptors)
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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.
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Small-molecule Neurotransmitters
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Amino acids – the building blocks of proteins
Monoamines – all synthesized from a single amino acid
Soluble gases
Acetylcholine (ACh) – activity terminated by enzymatic degradation
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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
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Effects tend to be diffuse
Catecholamines – synthesized from tyrosine
– Dopamine
– Norepinephrine
– Epinephrine
Indolamines – synthesized from tryptophan
– Serotonin (5-HT).
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Acetylcholine (Ach)
– Acetyl group + choline
– Neuromuscular junction
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Soluble gases – exist only briefly
– Nitric oxide and carbon monoxide
– Retrograde transmission – backwards communication
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Glutamate
Polyamine
Na +
Ca 2+
Zn 2+
PCP
Mg 2+
Ca 2+
CaM
Glycine /
D-Serine
PSD-95
NOS
NO *
L-Citruline
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L-Arginine

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What is the NMDAR System and
How Does it Function?
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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

Striatum Hippocampus

Pharmacology of Synaptic
Transmission
Many drugs act to alter neurotransmitter activity
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Agonists – increase or facilitate activity
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Antagonists – decrease or inhibit activity
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A drug may act to alter neurotransmitter activity at any point in its “life cycle”
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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
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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
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