COGNITIVE SCIENCE 17

The Chemical Brain

Part 1

Jaime A. Pineda, Ph.D.

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

Enzy

me(

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

EnkephalinsEndorphinsDynorphins

(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