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

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

Breakdown Products

Transmitter

Enz

yme(

s)

• Destruction • Reuptake

More on Receptors

• Gating– Ligand (activated by NT or drug)

– Voltage (activated by depolarization)

• Location– Postsynaptic

– Presynaptic

• Autoreceptor

• Heteroreceptor

PresynapticAutoreceptor=

PresynapticHeteroreceptors

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 AcidsGlutamate (Glu)

GABA

Biogenic AminesQuaternary Amines

Acetylcholine (Ach)

Monoamines

CatecholaminesDopamine (DA)

Norepinephrine (NE)

IndolaminesSerotonin (5-HT)

NeuropeptidesOpioid Peptides

Enkephalins

Endorphins

Dynorphins

(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