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Block 4: Unit 1B
Introduction to Neurotransmitters & Neuromodulators, Focus on Acetylcholine
48
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Undergraduate 4
12/11/2016

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Term
5 qualities a candidate neurotransmitter must have
Definition
1. be present inside the presynaptic neuron
2. have the same action as stimulating the presynaptic neuron
3. be released from the presynaptic nerve
4. be synthesized by the presynaptic neuron
5. the action of the neurotransmitter should be terminated quickly
Term
neurotransmitter
Definition
transmits a signal from one neuron to another
Term
neuromodulator
Definition
modulates & changes behavior
Term
Must a ligand be either a neurotransmitter or a neuromodulator?
Definition
no! (it can be both)
Term
four general classes of neurotransmitters/neuromodulators
Definition
type 1: "classical" neurotransmitters
type 2: amino acids
type 3: peptide neurotransmitters
type 4: gaseous neurotransmitters
Term
"classical" neurotransmitters: 3 examples
Definition
ACh, GABA, catecholamines
Term
"classical" neurotransmitters: molecule size?
Definition
small
Term
"classical" neurotransmitters: charged or uncharged?
Definition
charged
Term
"classical" neurotransmitters: uniquely synthesized?
Definition
yes!
Term
"classical" neurotransmitters: in vesicles?
Definition
yes!
Term
amino acids: 2 examples
Definition
glycine, glutamate
Term
amino acids: molecule size?
Definition
small
Term
amino acids: charged or uncharged?
Definition
charged
Term
amino acids: uniquely synthesized?
Definition
no!
Term
amino acids: in vesicles?
Definition
yes!
Term
peptide neurotransmitters: general number of amino acids
Definition
3 - 50
Term
peptide neurotransmitters: molecule size?
Definition
large
Term
peptide neurotransmitters: charged or uncharged?
Definition
charged
Term
peptide neurotransmitters: uniquely synthesized?
Definition
no!
Term
peptide neurotransmitters: in vesicles?
Definition
no!
Term
acetylcholine synthesis process
Definition
choline + acetyl-CoA <-- (via ChAT) --> ACh
Term
2 qualities of the HACU (high affinity choline uptake) transporter?
Definition
1. high-affinity for choline
2. low-efficiency
Term
3 steps to make acetyl choline in the presynaptic nerve terminal
Definition
1. choline & sodium ions in via the HACU transporter
2. choline & acetyl-CoA come together on ChAT
3. ACh is produced
Term
Where is acetyl-CoA made?
Definition
inside cell in mitochondria
Term
Is ChAT linked closely with HACU?
Definition
yes!
Term
The ______ will usually dictate how much of a neurotransmitter will be made in that neuron; it is typically the rate limiting step in the transmitter synthesis
Definition
the first unique enzyme (or transporter)
Term
Can you stain for ACh?
Definition
no!
Term
Can ACh move through the membrane?
Definition
no! (it is a positively charged molecule)
Term
How many transporters are needed to package ACh into vesicles?
Definition
two
Term
2 transporters on the vesicle required to get ACh in
Definition
1. ATP-dependent ATPase
2. VAChT
Term
3 ways ACh concentration is regulated
Definition
1. ACh inhibits ChAT (stops synthesis of ACh)
2. availability of choline (if it isn't present, ACh can't be made)
3. more action potentials --> more HACU transporters (more ACh can be made)
Term
2 ways ACh response is terminated
Definition
1. AChE (acetylcholinesterase) (breaks up ACh in the synapse)
2. extracellular matrix in the synapse (complex of proteins that keep ACh in the synapse so they don't float away into the CSF)
Term
Which pesticides are linked with insecticide-induced cholinergic syndrome?
Definition
organophosphate (OP) insecticides
Term
5 main symptoms of cholinergic syndrome
Definition
1. problems with respiration
2. problems with heart rate
3. problems with muscles (ex. muscle twitches, cramps, weakness)
4. confusion
5. impaired memory
Term
2 main delayed effects of cholinergic syndrome
Definition
1. degeneration of axon (causes muscle weakness, numbness/"pins-and-needles" feelings, paralysis of limbs
2. break down presynaptic terminals
Term
2 pharmacological treatments for cholinergic syndrome
Definition
1. muscarinic antagonists (ex. atrophine)
2. AChE reactivator
Term
Where does ACh go in the brain?
Definition
ALL OVER
Term
Diffuse ACh projections go mainly to the ______
Definition
forebrain
Term
ACh acts more in a _____ fashion
Definition
paracrine
Term
3 main effects of ACh in the forebrain
Definition
1. memory
2. cognition
3. learning
Term
ACh acts in a ______ role in the forebrain
Definition
neuromodulatory
Term
Blocking presynaptic receptors where ACh acts as a neuromodulator --> ?
Definition
loss of ability to create new memories (in normal people)
Term
How is the ChAT/HACU ACh pathway across synapse presynaptic to postsynaptic affected in AD patients?
Definition
decreased
Term
5 phases of drug development
Definition
1. preclinical
2. phase 1
3. phase 2 - on patients
4. phase 3 (farthest step for all drugs except cholinergic ones)
5. phase 4- can actually get approved by the FDA (farthest step for cholinergic ones)
Term
What are the only drugs that have been able to treat people with AD symptoms?
Definition
cholinergic
Term
In Alzheimer's, clumps of ______ proteins clog up brain & poison cells
Definition
amyloid
Term
Alzheimer's drugs aim to destroy _____ cells
Definition
dementia
Term
The antibody _____ reduces alpha beta plaques in Alzheimer's disease
Definition
aducanumab
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