GSU NEUR 3000 - NEUR 3000 - Chapter 6 (37 pages)

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NEUR 3000 - Chapter 6



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NEUR 3000 - Chapter 6

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Pages:
37
School:
Georgia State University
Course:
Neur 3000 - Hon Principles of Neuroscience
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NEUROTRANSMITT ER SYSTEMS NEUR 3000 Dr Joseph J Normandin PRINCIPLES OF NEUROTRANSMITTER SYSTEMS There are three classes of neurotransmitters Amino acids Amines Peptides there s probably more Within these classes there is a multitude of neurotransmitters Each neurotransmitter is part of a system that includes The molecule itself Synthesis of the neurotransmitter Packaging Reuptake degradation Action PRINCIPLES OF NEUROTRANSMITTER SYSTEMS There are three criteria that define a neurotransmitter Synthesis and storage in presynaptic neurons Released by a presynaptic axon terminal Produces a response in a postsynaptic cell Neurotransmitters bind to specific receptors There are many receptor subtypes for a given neurotransmitter Receptors can be transmitter gated ion channels ionotropic or g protein coupled receptors metabotropic The receptor determines neurotransmitter action A given neurotransmitter can have opposing actions depending on the receptor PRINCIPLES OF NEUROTRANSMITTER SYSTEMS PRINCIPLES OF NEUROTRANSMITTER SYSTEMS Exogenous molecules also interact with neurotransmitter receptors Any compound that binds to a receptor is a ligand Exogenous ligands that mimic the effect of a neurotransmitter are called agonists Exogenous ligands that block the effects of a neurotransmitter are called antagonists PRINCIPLES OF NEUROTRANSMITTER SYSTEMS PRINCIPLES OF NEUROTRANSMITTER SYSTEMS Neurotransmitter systems are defined by neurons that release a particular neurotransmitter Dopaminergic neurons GABAergic neurons However a given amine or amino acid neurotransmitter system may also co release with peptide neurotransmitters NEUROTRANSMITTER CHEMISTRY Acetylcholine ACh Amine neurotransmitter Cholinergic neurons Found in Motor neurons of the neuromuscular junction Central nervous system Autonomic nervous system NEUROTRANSMITTER CHEMISTRY NEUROTRANSMITTER CHEMISTRY NEUROTRANSMITTER CHEMISTRY Acetylcholine ACh In Alzheimer s disease there is death of CNS ACh neurons Drugs that inhibit AChE are effective in treating the memory deficits early on How NEUROTRANSMITTER CHEMISTRY Catecholamines Amine neurotransmitters Dopamine DA Norepinephrine NE Epinephrine E Catecholaminergic neurons Dopaminergic Noradrenergic Adrenergic Found in Central nervous system DA NE E mood arousal movement Autonomic nervous system NE visceral responses May also act as hormones NE E visceral responses NEUROTRANSMITTER CHEMISTRY NEUROTRANSMITTER CHEMISTRY Catecholamines Catecholamines are not degraded in the synaptic cleft Termination of catecholaminergic signals is dependent on reuptake transporters Back inside the axon terminal monoamine oxidase MAO will degrade catecholamines Dopaminergic cell death is a hallmark of Parkinson s disease Treatment in early Parkinson s is with L dopa What does that do NEUROTRANSMITTER CHEMISTRY Serotonin 5 hydroxytryptamine 5 HT Amine neurotransmitter Serotonergic neurons Found in Central nervous system though few in number Important in the regulation of mood emotion sleep NEUROTRANSMITTER CHEMISTRY NEUROTRANSMITTER CHEMISTRY Serotonin 5 hydroxytryptamine 5 HT Not degraded in the synaptic cleft Termination of serotonergic signals is dependent on reuptake transporters Back inside the axon terminal monoamine oxidase MAO will degrade 5 HT Blocking of the 5 HT transporter by SSRIs is the most common method of pharmacological intervention for depression What does that do NEUROTRANSMITTER CHEMISTRY Amino acid neurotransmitters Glutamate Glu Glycine Gly gama Aminobutyric acid GABA Amino acidergic neurons Glutamatergic Glycinergic GABAergic Found Ubiquitously in central nervous system Glutamate is the major excitatory NT of the brain GABA is the major inhibitory NT of the brain NEUROTRANSMITTER CHEMISTRY NEUROTRANSMITTER CHEMISTRY Amino acid neurotransmitters Not degraded in the synaptic cleft Termination of amino acidergic signals is dependent on reuptake transporters on neurons and glia Back inside the axon terminal or glia GABA transaminase will degrade GABA Glu Gly are recycled NEUROTRANSMITTER CHEMISTRY Other neurotransmitters ATP Found in presynaptic terminals in CNS PNS Released with calcium influx Co released with catecholamines at some synapses Binds to purinergic receptors ionotropic and metabotropic NEUROTRANSMITTER CHEMISTRY Other neurotransmitters Endocannabinoids Small lipid molecules Retrograde transmitter from postsynaptic cell to presynaptic terminal Regulates NT release at presynaptic terminal Synthesized from membrane via a specific enzyme Released w o vesicle Bind to CB1receptor metabotropic inhibits calcium channel opening What would this do TRANSMITTER GATED CHANNELS Transmitter gated ion channels are a type of receptor Binding of a ligand results in the opening of an ion channel Also called ligand gated ion channels ionotropic receptors Considered to be fast synaptic transmission Channel selectivity for different ions determines the effect of ligand binding TRANSMITTER GATED CHANNELS Ionotropic glutamate receptors AMPA NMDA Kainate receptors Originally defined by the exogenous ligands that activated these receptors in experimental preparations AMPA NMDA receptors produce fast excitatory transmission in the brain AMPA receptors Selective for Na K EPSP Co expressed with NMDA receptors NMDA receptors Selective for Na K Ca2 EPSP other actions Voltage dependent Mg2 block Say what TRANSMITTER GATED CHANNELS TRANSMITTER GATED CHANNELS TRANSMITTER GATED CHANNELS Ionotropic GABA Glycine receptors GABA makes up the majority of fast inhibitory transmission in the brain glycine the rest GABA and glycine receptors are selective for Cl IPSP Many exogenous ligands bind to the GABAA receptor and enhance IPSPs Benzodiazepines valium GABA Increase frequency of channel openings Barbiturates phenobarbital GABA Increase duration of channel opening Ethanol also a GABAA agonist All of these exogenous ligands bind to their own specific site on the receptor different than where GABA binds Are there endogenous ligands for these sites Neurosteroids TRANSMITTER GATED CHANNELS G PROTEIN COUPLED RECEPTORS G protein coupled receptors GPCRs are another type of receptor Binding of a ligand results in the activation of g proteins which can have a variety of effects via effector proteins Also commonly called metabotropic receptors Considered to be slow synaptic transmission but effects can be long lasting and amplified by signaling cascades G protein is short for guanosine triphosphate GTP binding protein


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