PSY236 Lecture Notes - Lecture 10: Rate Limiting, Perceptual Learning, Butyric Acid
2 Jun 2018
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Week 10 Lectures: Neurotransmitters
Action potential = neurotransmitter release
• 1. Action potential
• 2. Vesicle docks
• 3. NT release (Exocytosis)
• 4. NT binds to receptor
• 5. Unbound NT transported into presynaptic terminal (reuptake = endocytosis)
• 6. NT gets broken down or repackaged in vesicles
What makes a neurotransmitter a neurotransmitter?
• There are 5 rules to being a true ‘classical’ chemical neurotransmitter
1. The chemical must exist (made and stored) in presynaptic cells (stored in
terminals)
2. The chemical must be released from presynaptic terminals on action
potential
3. Released chemical must bind to receptors and cause a biological effect
4. There must be a mechanism to inactive or metabolise the chemical
5. The chemical should have the same biological effect if artificially applied
to synapse (e.g. by microinjection to brain area – exogenously applied)
Neurotransmitter (NT) requirements
• A. chemical exists presynaptic (NT release – exocytosis)
• B. Release on action potential
• C. Act on receptor = biological effect
• D. Metabolism/inactivation (NT gets broken down or repackaged in vesicles)
o Inactivation – unbound NT transported into presynaptic terminal
(reuptake = endocytosis)
• E. Application of exogenous chemical produces same effect
Where do neurotransmitters come from?
• Peptides
o Precursor peptide (small protein) synthesized in rough ER
o Cleaved in Golgi apparatus to active neurotransmitter
o Secretory vesicles bud off from Golgi apparatus
o Secretory granules (large vesicles, 100 nm) transported to terminal and
stored
• Monoamines, amino acids and acetylcholine
o Precursor molecule (from diet) synthesized to neurotransmitter
o Transported to synaptic vesicle (50 nm) and stored
Main difference between peptides and monoamines, amino acids or acetylcholine
neurotransmitters:
• Peptide neurotransmitters are made in the soma and transported in secretory
granules to the terminal
• Monoamines, amino acids and acetylcholine are made from precursor
molecules in the terminal and are transported into synaptic vesicles
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The life of a neurotransmitter
• Peptides made in the soma
• Peptides are transported
• Acetylcholine too, monoamines/amino acids made in terminals
• Stored in vesicles
• Released
• Metabolized or reuptake
What are the neurotransmitters?
• Amino acids
• Acetylcholine
• Monoamines/trace amines
• Peptides e.g. substance P
• Lipids e.g. Anandamide
• Nucleosides e.g. ATP
• Soluble gases e.g. Nitric Oxide: Viagra
Major roles
• Glutamate → major excitatory NT, learning and memory, neuroplasticity,
excitotoxicity
• Dopamine → short term memory, strategy and planning, reward, movement
• Serotonin → cognition, emotion, reward
• Noradrenaline → attention, flight/fight, sleep
• GABA → major inhibitory NT, modulator of many processes
• Acetylcholine → memory, perceptual learning, movement, REM sleep
Common amino acid neurotransmitters
• Glutamate Aspartate + Gamma Amino Butyric Acid
• GABA
• Glycine
o Brainstem spinal cord
Where are the cell bodies?
• GABA is also found in interneurons
Many GABA interneurons
• Interneurons are small neurons retained in the one brain area
• GABA or Acetylcholine are commonly in interneurons
Synthesis
• Glutamate, aspartate and glycine are common amino acids used in protein
synthesis, synthesised from glucose
• GABA is a specific amino acid present only in GABA cells
o Glutamate (glutamic acid decarboxylase) → GABA
• Immunostaining for GAD can be used to identify GABA neurons
Metabolism
• Terminal → GABA transaminase breaks down GABA
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find more resources at oneclass.com
• Glial cell → GABA transaminase breaks down GABA
• Glutamate is recycled
• GABA or glutamate reuptake (transporters)
• Postsynaptic density/dendrite
o Glutamate is neurotoxic (kills neurons) in high amounts – glial cells
work to reduce toxic levels
Major roles
• Acetylcholine → memory, perceptual learning, movement, REM sleep
Where are the acetylcholine cell bodies?
• Striatal interneurons
• Nucleus basalis
• Septohippocampal pathway
Synthesis
• Acetylcholine (Ach) is predominantly excitatory (+)
• Ach is taken up by the Ach transporter into vesicles and stored
Metabolism
• Acetylcholine is broken down by Acetylcholine esterase
• Acetylcholine = choline & acetic acid
o Ach metabolism occurs in the synaptic left
o Choline is then transported into the presynaptic cell for re-use
• Many insecticides or nerve gases inhibit AChE
• Enhances Ach transmission at muscle and heart
• Death usually by respiratory paralysis
Acetylcholine life-cycle
• More choline detected in the synaptic cleft = reduces ACh production
• Rate limiting step is choline in synapse - inversely related (negative feedback)
Major roles
• Dopamine → short term memory, strategy and planning, reward, movement
• Serotonin → cognition, emotion, reward
• Noradrenaline → attention, flight/fight, sleep
3 Catecholamines + 2 Indolamines
• Catecholamines → dopamine → noradrenaline → adrenalin (hormone from
kidney; adrenal)
• Indoalmines → serotonin → melatonin (circadian rhythms) → histamine
(wakefulness, low levels in brain, posterior hypothalamus) → forebrain
Where are the dopamine and noradrenaline cell bodies?
• Noradrenaline → found in locus coeruleus and caudal raphe nuclei
• Dopamine → found in ventral tegmental area and substantia nigra (also in
nigostriatal system and mesolimbic system)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Neurotransmitter (nt) requirements: a. chemical exists presynaptic (nt release exocytosis, b. The life of a neurotransmitter: peptides made in the soma, peptides are transported, acetylcholine too, monoamines/amino acids made in terminals, stored in vesicles, released, metabolized or reuptake. What are the neurotransmitters: amino acids, acetylcholine, monoamines/trace amines, peptides e. g. substance p, lipids e. g. anandamide, nucleosides e. g. atp, soluble gases e. g. nitric oxide: viagra. Common amino acid neurotransmitters: glutamate aspartate + gamma amino butyric acid, gaba, glycine, brainstem spinal cord. Where are the cell bodies: gaba is also found in interneurons. Interneurons are small neurons retained in the one brain area: gaba or acetylcholine are commonly in interneurons. Synthesis: glutamate, aspartate and glycine are common amino acids used in protein synthesis, synthesised from glucose, gaba is a specific amino acid present only in gaba cells, glutamate (glutamic acid decarboxylase) gaba. Immunostaining for gad can be used to identify gaba neurons. Major roles: acetylcholine memory, perceptual learning, movement, rem sleep.
