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Neurotransmitters I

Neurotransmitters I. The Life Cycle of a Conventional NT. Biosynthesis & Storage Release Receptor Action Inactivation. Transmitter. Enzyme(s). Biosynthesis. Precursor(s). Storage. Synaptic vesicles made by Golgi apparatus in cell body

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Neurotransmitters I

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  1. Neurotransmitters I

  2. The Life Cycle of a Conventional NT • Biosynthesis & Storage • Release • Receptor Action • Inactivation

  3. Transmitter Enzyme(s) Biosynthesis Precursor(s)

  4. Storage • Synaptic vesicles made by Golgi apparatus in cell body • Precursors, enzymes, and vesicles are transported from cell body down axon to terminal • At terminal, NTs are synthesized and packaged into vesicles • Filled vesicles dock onto proteins in terminal

  5. Release • Action potential opens channels for Ca++ to enter terminal membrane • Vesicles to undock and move to membrane • Vesicles fuse with membrane and empty transmitter into synapse (exocytosis)

  6. Receptor Action • Ionotropic • Opens ion channel in receptor itself • Ions produce either excitation or inhibition • Fast action • Metabotropic • Sets off cascade of chemical events • Can lead to ion channel opening on another protein • Can lead to other, long-term changes • Slower action

  7. Transmitter Enzyme(s) Breakdown Products Inactivation • Destruction • Reuptake

  8. More on Receptors • Gating • Ligand (activated by NT or drug) • Voltage (activated by depolarization) • Location • Postsynaptic • Presynaptic • Autoreceptor • Heteroreceptor

  9. Presynaptic Autoreceptor =

  10. Presynaptic Heteroreceptors

  11. Some Receptor and Other Changes • Receptor number (up/down-regulation) • Receptor affinity (low/high) • Reuptake transporter number/affinity • Enzyme levels • Transmitter synthesis • Axon growth • Dendrite growth • Etcetera

  12. Hierarchy of NTs of Interest Amino Acids Glutamate (Glu) GABA Biogenic Amines Quaternary Amines Acetylcholine (Ach) Monoamines Catecholamines Dopamine (DA) Norepinephrine (NE) Indolamines Serotonin (5-HT) Neuropeptides Opioid Peptides Enkephalins Endorphins Dynorphins (Others: lipids, nucleosides, soluble gases)

  13. Amino Acid NTs • High concentration in brain (micromolar) • Small vesicles • Point-to-point communication • Mostly cortex-to-cortex • Sensory-motor functions • Consistently excitatory or inhibitory • Mainly ionotropic receptors • Fast acting, short duration (1-5 ms) • Examples: Glutamate, Aspartate, GABA, Glycine

  14. Biogenic Amines • Medium concentration in brain (nanomolar) • Small vesicles • Single-source divergent projections • Mainly midbrain to cortex • Modulatory functions • Excitatory or inhibitory by receptor • More metabotropic receptors than ionotropic, but plenty of both • Slow acting, long duration (10-1000 ms) • Examples: Acetylcholine, Epinephrine, Norepinephrine, Dopamine, Serotonin

  15. Neuropeptides • Low concentration in brain (picomolar) • Large vesicles • Packaged in vesicles before transport to terminal • Co-localized with other transmitters • Interneuronal • Modulatory functions • Mostly inhibitory • Virtually all metabotropic • Slow acting, long duration (10-1000 ms) • Examples: Enkephalins, Endorphins, Oxytocin, Vasopressin

  16. Modulatory Functions • State-dependent effects • Regulate influence of extrinsic vs. intrinsic activity • Synchronization of areas/functions • Motivational/emotional recruitment of mental resources

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