Neurotransmitters I The Life Cycle of a Conventional NT Biosynthesis & Storage Release Receptor...
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Transcript of Neurotransmitters I The Life Cycle of a Conventional NT Biosynthesis & Storage Release Receptor...
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Neurotransmitters I
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The Life Cycle of a Conventional NT
• Biosynthesis & Storage
• Release
• Receptor Action
• Inactivation
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Biosynthesis
Precursor(s) Transmitter
Enzyme(s)
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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
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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)
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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
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Inactivation
Breakdown Products
Transmitter
Enz
yme(
s)
• Destruction • Reuptake
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More on Receptors
• Gating– Ligand (activated by NT or drug)
– Voltage (activated by depolarization)
• Location– Postsynaptic
– Presynaptic
• Autoreceptor
• Heteroreceptor
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PresynapticAutoreceptor=
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PresynapticHeteroreceptors
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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
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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)
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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
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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
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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
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Modulatory Functions
• State-dependent effects
• Regulate influence of extrinsic vs. intrinsic activity
• Synchronization of areas/functions
• Motivational/emotional recruitment of mental resources
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