Ch06

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Ch06

  1. 1. NEUROTRANSMITTER SYSTEMS
  2. 2. NEUROTRANSMITTERBasic criteria:1. The molecule must be synthetized and stored in the presynaptic neuron2. The molecule must be released by the presynaptic axon terminal uponstimulation3. The molecule, when experimentally applied, must produce a response in thepostsynaptic cell that mimics the response generated by the release of theneurotransmitter by the presynaptic cell
  3. 3. HOW TO STUDY NEUROTRASMITTERSLocalization of Transmitters and Transmitter-synthesizing enzyme Immunocytochemistry Anatomically localize particular molecules to particular cells
  4. 4. HOW TO STUDY NEUROTRASMITTERSStudying Transmitter Localization In situ hybridization mRNA strands can be detected by complementary probe Probe can be radioactively labeled - autoradiography
  5. 5. HOW TO STUDY NEUROTRASMITTERSStudying 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 vitro  Stimulate 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
  6. 6. HOW TO STUDY NEUROTRASMITTERSStudying Receptors No two transmitters bind to the same receptor; however one neurotransmitter can bind to many different receptors Receptor subtypes Neuropharmacology Subtype specific agonists and antagonists ACh receptors Skeletal muscle Heart
  7. 7. HOW TO STUDY NEUROTRASMITTERSStudying Receptors
  8. 8. HOW TO STUDY NEUROTRASMITTERSStudying ReceptorsLigand-binding methods Drugs that interact selectively with neurotransmitter receptors were used to analyze natural receptors Solomon Snyder and opiates Identified receptors in brain Subsequently found endogenous opiates Endorphins, dynorphins, enkephalins Enormously important for mapping the anatomical distribution of different neurotransmitter receptors in brain
  9. 9. NEUROTRASMITTER CHEMISTRYCholinergic (ACh) Neurons good marker for cholinergic neurons Rate-limiting step of Ach synthesis Secreted from the axon terminal and associated with axon terminal membrane
  10. 10. NEUROTRASMITTER CHEMISTRYCholinergic (ACh) Neurons Synthesis Degradation
  11. 11. NEUROTRASMITTER CHEMISTRYCatecholaminergic 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)
  12. 12. NEUROTRASMITTER CHEMISTRY Marker for catecholaminergic neurons Rate limiting, regulated by physiological signals •Low-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 cytosolReleased from the adrenal gland as well
  13. 13. NEUROTRASMITTER CHEMISTRY• 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
  14. 14. NEUROTRASMITTER CHEMISTRY• Amino Acidergic Neurons – Amino acid neurotransmitters: Glutamate, glycine, gamma- aminobutyric acid (GABA) – Glutamate and glycine • Present in all cells - Differences among neurons are quantitative NOT qualitative • Vesicular transporters are specific to these neurons – Glutamic acid decarboxylase (GAD) • Key enzyme in GABA synthesis • Good marker for GABAergic neurons • One chemical step difference between major excitatory transmitter and major inhibitory transmitter

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