Definition of Neurotransmitter

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Definition of Neurotransmitter

• Synthesized in the neuron
• Present in the presynaptic terminal and released
  in sufficient amounts to effect the post-synaptic
  neurons or effector organ
• Exogenous application mimics the action of
  released neurotransmitter
• Specific mechanism exists for removing it from
  synaptic cleft.

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Vesicles - EM

• Small clear vesicles
• small molecule transmitters
• 40-60 nm

• Dense core vesicles
• peptides
• 90-250 nm
• biogenic amines
• 40-120 nm
• often irregularly shaped

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Acetylcholine
Amino Acid Transmitters
Biogenic Amine Transmitters
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• Amino Acid Transmitters
• Glutamate
• most frequently used neurotransmitter
• GABA (?-aminobutyric acid)
• most common inhibitory neurotransmitter in brain
• Glycine
• major inhibitory neurotransmitter in spinal cord
• Aspartate

Glutamic Acid Decarboxylase
- requires B6 cofactor
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• Glutamate is present in high concentration in ALL
  cell, because it is synthesized by normal
  metabolism in all neurons (even
  non-glutamatergic), but it is stored in vesicle
  only in part of them (glutamatergic neurons)

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GABA synthesis enzyme and transporter are
colocalized in hippocampus neurons.
GAD
GAT-1
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Acetylcholine

• Neuromuscular junction
• Parasympathetic post ganglionic neurons
• Cholinergic brainstem nuclei
• Nucleus basalis

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Cholinergic nuclei
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Catecholamines

• Dopamine, Norepinephrine, Epinephrine

Tyrosine hydroxylase - rate-limiting
DOPA Decarboxylase
Dopamine ?-hydroxylase - associated with
vesicles - Norepinephrine is the only
transmitter made in vesicle
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Synthesis of catecholamines
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• Dopamine
• Substantia nigra - Parkinsons disease
• Ventral tegmentum - schizophrenia
• Hypothalamus - autonomic and endocrine function
• Norepinephrine
• locus ceruleus
• 10,000 neurons project to every major region of
  brain and spinal cord
• Regulate vigilance and responses to novel stimuli
• Sympathetic post ganglionic neurons
• Epinephrine
• Few neurons make it

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Two dopaminergic Systems 1) Sbst. Nigra to
Basal Ganglia 2) VTA to Accumbens, Prefrontal
CTX , Thal, Hippocampus etc
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Noradrenergic system
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• Histamine
• Mast cells
• Hypothalamus
• regulates behavioral arousal

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Histaminergic system
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• Serotonin
• Raphe nucleus
• widely distributed to brain and spinal cord
• regulates attention and other cognitive functions
• implicated in depression
• Fluoxetine serotonin reuptake inhibitors

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Serotoninergic system
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Neurotransmitter transport and re-uptake
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Glycine
GABA
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Vesicle transporter
Transmitter concentration in synaptic vesicles is
50-100mM Vesicular transport is pH-dependent
Vesicular ATP-ase
Glutamate transporter
Other transporters Acetylcholine transporter
GABA/Glycine transporter - Related to bacterial
drug-resistance transporters
Amine transporter
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Transmitter Removal

• Diffusion
• Enzymatic degradation
• Re-uptake

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• Peptides transmitters

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Peptides are made and packaged in the cell body,
and taken to presynaptic terminals via fast
axonal transport. No peptide reuptake or
membrane recycling. Peptide release requires
general, rather than local, rise in Ca2 levels.
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A large number of neuroactive peptides have been
charachterized
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Peptides are often cleaved from pro-peptides
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Nitric Oxide

• Membrane permeable gas
• Made by nitric oxide synthase
• Functions both as a neurotransmitter and a second
  messenger

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Involvement of Ca2 channels In
neuro-transmitter release
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Capacitance measurements indicate exocitosis
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Voltammetry measurement of charged
neurotransmitter exocytosis
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Presynaptic inhibition

• Activate metabotropic receptors that close Ca2
  channels and open more K channels
• Activation of ionotropic Cl- channels
• Activate metabotropic receptors that inhibit the
  release machinery

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Short-term Synaptic plasticity
Two responses to the SAME stimulus are not
necessarily the same probably because of the
accumulation of Ca2 in the presyn terminal
following one or more APs
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