Chapter 6 Neurotransmitter Systems. Introduction Three classes of neurotransmitters –Amino acids,...
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Transcript of Chapter 6 Neurotransmitter Systems. Introduction Three classes of neurotransmitters –Amino acids,...
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Chapter 6 Neurotransmitter Systems
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Introduction
• Three classes of neurotransmitters– Amino acids, amines, and peptides
• Ways of defining particular transmitter systems:– By the molecule, synthetic machinery, packaging,
reuptake and degradation, etc.
• Acetylcholine (Ach)– First identified neurotransmitter
• Nomenclature (-ergic) – Cholinergic and noradrenergic
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Henry Dale – received the Nobel Prize for Medicine in 1926 for his work on synaptic transmission.
He is also well known for his coining of the term “cholinergic.”
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• Studying Transmitter Localization
• Immunocytochemistry – localize molecules to cells
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• In situ hybridization– Localize synthesis of protein or peptide to a
cell (detect mRNA)
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Muscarine – a type of poison found in some mushrooms
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Moto-Taxi Driver (1999) at a coffee shop in Bangalore, IndiaHe is stimulating his nicotinic receptors.
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A farmer harvesting opium poppies.
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Studying Neurotransmitter Systems
• Neurotransmitter - three criteria– Synthesis and storage in presynaptic neuron– Released by presynaptic axon terminal– Produces response in postsynaptic cell
• Mimics response produced by release of neurotransmitter from the presynaptic neuron
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• Studying Transmitter Release
– Transmitter candidate: Synthesized and localized in terminal and released upon stimulation
– CNS contains a diverse mixture of synapses that use different neurotransmitters
– Brain slice as a model• Kept alive in vitro Stimulate synapses,
collect and measure released chemicals
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• Studying Synaptic Mimicry
– Qualifying condition: Molecules evoking same response as neurotransmitters
– Microionophoresis: Assess the postsynaptic actions– Microelectrode: Measures effects on membrane
potential
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• Studying Receptor Subtypes– Neuropharmacology
• Agonists and antagonists
• e.g., ACh receptors – Nicotinic,
Muscarinic• Glutamate receptors
– AMPA, NMDA, and kainite
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– Ligand-binding methods• Identify natural receptors using
radioactive ligands •Can be: Agonist, antagonist, or
chemical neurotransmitter
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– Molecular analysis- receptor protein classes– Transmitter-gated ion channels
» GABA receptors» 5 subunits, each made with 6 different
subunit polypeptides– G-protein-coupled receptors
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Neurotransmitter Chemistry
• Evolution of neurotransmitters– Neurotransmitter molecules
• Amino acids, amines, and peptides • Dale’s Principle
– One neuron, one neurotransmitter• Co-transmitters
– Two or more transmitters released from one nerve terminal
– An amino acid or amine plus a peptide
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Neurotransmitter Chemistry
• Cholinergic (ACh) Neurons
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Neurotransmitter Chemistry
• Cholinergic (ACh) Neurons
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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)• Epinephrine (E,
adrenaline)
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• Serotonergic (5-HT) Neurons– Amine neurotransmitter
• Derived from tryptophan– Regulates mood, emotional behavior, sleep
• Selective serotonin reuptake inhibitors (SSRIs) - Antidepressants
– Synthesis of serotonin
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• Amino Acidergic Neurons– Differences among amino acidergic neurons
quantitative NOT qualitative – Glutamic acid decarboxylase (GAD)
• Key enzyme in GABA synthesis• Good marker for GABAergic neurons• GABAergic neurons are major of synaptic
inhibition in the CNS
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• Other Neurotransmitter Candidates and Intercellular Messengers– ATP: Excites
neurons; Binds to purinergic receptors
– Endocannabinoids– Retrograde
messengers
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Consumption of Cannabis:
Effect is due to its ability to alter neural activity in the brain in ways similar to several different neurotransmitters
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Transmitter-Gated Channels
• Introduction– Fast synaptic transmission– Sensitive detectors of chemicals and voltage– Regulate flow of large currents– Differentiate between similar ions
• The Basic Structure of Transmitter-Gated Channels– Pentamer: Five protein subunits
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Transmitter-Gated Channels
• Amino Acid-Gated Channels– Glutamate-Gated Channels
• AMPA, NMDA, kainite
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Transmitter-Gated Channels
• Amino Acid-Gated Channels– GABA-Gated and Glycine-Gated Channels
• GABA mediates inhibitory transmission • Glycine mediates non-GABA inhibitory
transmission• Bind ethanol, benzodiazepines, barbiturates
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• GPCR Effector Systems– The Shortcut Pathway
• From receptor to G-protein to ion channel; Fast and local
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• GPCR Effector Systems– Second Messenger Cascades
• G-protein: Couples neurotransmitter with downstream enzyme activation
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• GPCR Effector Systems (Cont’d)• Push-pull method (e.g., different G proteins or
stimulate and inhibit adenylyl cyclase)
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• Divergence– One transmitter
activates more than one receptor subtype greater postsynaptic response
• Convergence– Different
transmitters converge to affect same effector system
Divergence and Convergencein Neurotransmitter Systems
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Concluding Remarks
• Neurotransmitters– Transmit information between neurons– Essential link between neurons and effector
cells• Signaling pathways
– Signaling network within a neuron somewhat resembles brain’s neural network
– Inputs vary temporally and spatially to increase and/or decrease drive
– Delicately balanced– Signals regulate signals- drugs can shift the
balance of signaling power