CH06

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NEUROTRANSMITTER SYSTEMS

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NEUROTRANSMITTER

Basic criteria:

1. The molecule must be synthetized and stored in the presynaptic neuron

2. The molecule must be released by the presynaptic axon terminal upon

stimulation

3. The molecule, when experimentally applied, must produce a response in the

postsynaptic cell that mimics the response generated by the release of the

neurotransmitter by the presynaptic cell

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HOW TO STUDY NEUROTRASMITTERS

Localization of Transmitters and Transmitter-synthesizing enzyme

Immunocytochemistry

Anatomically localize particular molecules to particular cells

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Studying Transmitter Localization

In situhybridization

mRNA strands can be detected by complementary probeProbe can be radioactively labeled - autoradiography

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Studying Transmitter Release

Loewi and Dale identified Ach as a transmitter

CNS contains a diverse mixture of synapses that use different

neurotransmitters

impossible to stimulate a single population of synapses

Brain slice as a model (ex vivo,brain in a dish)

Kept alive in vitroStimulate synapses, collect and measure

released chemicals (mixture)

Often stimulated by high K+solution to cause massive synaptic release

Ca2+ dependency of the release has to be confirmed

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Studying Receptors

No two transmitters bind to the same receptor; however one neurotransmittercan bind to many different receptors

Receptor subtypes

Neuropharmacology

Subtype specific agonists and antagonists

ACh receptors

Skeletal muscle Heart

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Studying Receptors

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Studying Receptors

Ligand-binding methodsDrugs that interact selectively with neurotransmitter receptors were used

to analyze natural receptors

Solomon Snyder and opiates

Identified receptors in brain

Subsequently found endogenous opiatesEndorphins, dynorphins, enkephalins

Enormously important for mapping the anatomical distribution of different

neurotransmitter receptors in brain

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NEUROTRASMITTER CHEMISTRY

Cholinergic (ACh) Neurons

good marker for cholinergic neurons

Rate-limiting step ofAch synthesis

Secreted from the axonterminal and associated with

axon terminal membrane

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Cholinergic (ACh) NeuronsCholinergic (ACh) Neurons

Synthesis

Degradation

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Catecholaminergic Neurons

Involved in movement, mood, attention,

and visceral function

Tyrosine: Precursor for three amine

neurotransmitters that contain catechol

group

Dopamine (DA)

Norepinephrine (NE, noradrenaline)

Epinephrine (E, adrenaline)

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Marker for catecholaminergic neurons

Rate limiting, regulated by

physiological signalsLow-rate release - increased

catecholamine conc. - inhibit TH activity

High-rate release - increased Ca2+ influx

- boost TH activity

Present in the synaptic vesicles

Present in the cytosol

Released from the adrenal gland as well


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Serotonergic Neurons Serotonin (5-HT,5-

hydroxytryptamine) is derived

from tryptophan

Regulates mood, emotional

behavior, sleep Synthesis of serotonin

Limited by the availability of

blood tryptophan (diet)

Selective serotonin reuptake

inhibitors (SSRIs):Antidepressants


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Amino Acidergic Neurons

Amino acid neurotransmitters:Glutamate, glycine, gamma-aminobutyric acid (GABA)

Glutamate and glycine

Present in all cells - Differencesamong neurons are quantitative

NOT qualitative Vesicular transporters are specific

to these neurons

Glutamic acid decarboxylase (GAD)

Key enzyme in GABA synthesis

Good marker for GABAergicneurons

One chemical step differencebetween major excitatorytransmitter and majorinhibitory transmitter


CH06

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