Flipped lecture Synapses + NT Flashcards
What is ChAT?
Choline acetyltransferase
What is the role of Choline acetyltransferase?
ChAT catalyzes the transfer of an acetyl group from acetyl-CoA to choline, producing acetylcholine
Essentially synthesises ACh
Where is Acetyl Coa produced?
Produced by cellular respiration in mitochondria
Wat are nictonic acetylcholine receptors (nAChRs)?
nAChRs are a type of cholinergic receptors, meaning they respond to ACh
What happens to Ach?
AChe breaks down Ach into Chloine and Acetic acid which the choline is then reuptaked by choline transporter
How many types of Muscarinic receptors?
5
M1,M2,M3,M4,M5
Where are Musarinic (mAChRs) found?
Cns and autonomic nervous system
Which muscarinic receptors are excitatory and inhibitory?
M1, 3, 5: excitatory via Gq
M2, 4: inhibitory via GI
Are there more mAChRs (muscarinic) or nAChRs (nicotinic) in the brain?
Brain has 10-100x more mAChRs than nAChRs
What is the neurotransmitter at the NMJ?
Neuromuscular junction
Acetylcholine
What blocks the release of acetylchloine?
- Botulinum toxin - destroys SNARE’s protein
- Black widow spider venom - Causes large Ca2+ influx but then completely stops it
What blocks the AChE?
- Nerve gas
- Organophosphate pesticides
- Alzheimer’s treatments
Buildup of Ach resulting in excessive stimulation of ACh receptors
What activates ACh receptors?
- Nioctine, muscarine (agonists)
- Neonicotinioid pesticides
What blocks the ACh receptors?
- Nicotinic: curare, a-bungarotoxin
- Muscarinic: atropine
What 4 ways could interfere with Acetylcholine’s role?
1) Block release
2) Block AChE
3) Activate ACh receptors
4) Block Ach receptors
Why is atropine used to treat nerve gas poisoning?
- Nerve gases are potent inhibitors of AChE (breaks down ACh)
- Atropine is a muscarinic acetylcholine receptor antagonist - means it blocks ACh from binding to muscarinic receptors
Atropine acts as a competitive inhibitor, preventing the excess ACh from overstimulating the muscarinic receptors
What is VMAT?
Vesicular monoamine transporters
What gets packed into vesicles by VMAT?
Monoamines
What is MAO?
Monoamine oxidase
What can destroy monoamines?
Monoamina oxidase (MAO) and catechol-O-methyltransferase
What are monoamine receptors mostly like?
Monoamine receptors are mostly GPCRs
What are the receptors for epinephrine/ norepinephrine?
Adrenergic receptors: alpha and beta types
What are the receptors for Serotonin?
7 receptors - one is a ligand-gated Na+/K+ channel
Where is dopamine produced?
Produced in the substantia nigra
Where are dopaminergic neurons in the substantia nigra projected to?
They are projected to the striatum
What is the pathway responsible for motor movement called?
The nigrostriatal pathway
What happens if dopamingeric neurons are damaged?
Damage to the dopamine-producing neurons in the substantia nigra leads to a decrease in dopamine in the striatum, which is the primary cause of Parkinson’s disease
What is TH?
Tyrosine hydroxylase
Does dopamine cross the blood-brain barrier ?
No it does not cross
Why can Parkinson’s be treated by increasing dopamine?
Parkinson’s disease is primarily caused by the loss of dopamine-producing neurons in the substantia nigra, leading to a dopamine deficiency in the striatum.
This deficiency disrupts the delicate balance of neurotransmitters in the brain, resulting in the characteristic motor symptoms of Parkinson’s, such as tremors, rigidity, and slowness of movement.
Therefore, a major focus of Parkinson’s treatment is to increase dopamine levels in the brain to compensate for this loss
What is VTA?
Ventral tegmental area?
Where does the ventral tegmental area project to?
The VTA projects to the cortex and limbic system
What does the mesolimbic pathway mediate?
Reward/motivation
Where do noradrenergic neurons live?
They live in the locus coeruleus
How much noradrenergic neurons are there in the brain?
12,000 per hemisphere
What is the role of noradrenergic neurons in the brain?
Noradrenergic neurons, particularly those in the locus coeruleus, are vital in regulating wakefulness and vigilance.
They increase alertness and responsiveness to stimuli.
Also regulate sleep/wake, attention, arousal, mood, memory, anxiety, pain etc
Where do serotonergic neurons live?
They live in the Raphe nuclei
What is the role of serotonergic neurons?
Serotonin is heavily involved in regulating mood, feelings of well-being, and happiness.
mbalances in serotonin levels are often linked to mood disorders like depression and anxiety
What are monoamines?
Monoamines are neurotransmitters that contain one amino group connected to an aromatic ring by a two-carbon chain
What do cocaine and amphetamines do?
Block reuptake of dopamine and norepinephrine
What do antipsychotics do?
They block dopamine receptors (possible side effect: Parkinson’s-like symptoms)
Give me exampls of antidepressants
- Tricyclics: block reuptake of NE, serotonin
- Selective serotonin reuptake inhibitors (SSRIs), e.g. fluoxetine (Prozac)
- MAO-A inhibitors
