2. Neurotransmitters I

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

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

5. 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

6. 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)

9. 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

12. Inactivation Breakdown Products Transmitter Enzyme(s) DestructionReuptake

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

15. Presynaptic Autoreceptor =

16. Presynaptic Heteroreceptors

17. 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

19. 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)

20. 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

21. 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

22. 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

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