Neurotransmitters I The Life Cycle of a Conventional

Neurotransmitters I

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

Biosynthesis Precursor(s) Transmitter Enzyme(s)

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

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)

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

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

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

= Presynaptic Autoreceptor

Presynaptic Heteroreceptors

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

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

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

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

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

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