Transcript The Chemical Brain - Part 2

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
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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
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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
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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