Lecture 7

Question 1

Conventional neurotransmitters

Answer 1

Glutamate - Main excitatory transmitter in the brain

GABA - Main inhibitory transmitter in the brain

This means that when they interact with ionotropic receptors have these effects due to the ions they permit in
99 % of the neurons in the CNS use one or other of these. They might use another too but this one principally

Question 2

Main neuromodulators in the brain

Answer 2

Dopamine, Norepinephrine, acetylcholine, serotonin

Usually moderate post synoptic cells via metabotropic receptors

Question 3

Ach is special

Answer 3

Neuromodulator in CNS, often at axoaxonic synapses and vis metabotropic receptors

In PNS, released by motor neurons and acts on muscles via ionotropic receptors

Question 4

Glutamate details

Agonist/antagonist drug effects and examples

Answer 4

Excitatory
Ionotropic induce excitatory post synaptic currents
Depolarization

Agonists causes seizures and excitotoxicity) (kainic acid, MDMA)
Antagonists: Dissociative anesthetics (Ketamine, PCP)

Question 5

GABA details

Answer 5

Inhibitory
Ionotropic induce inhibitory post synaptic currents
Hyperpolarization

Agonists: anesthesia, anticonvulsants, muscle relaxants, sleeping pills, anxiolytics (alcohol, barbiturates, benzos)
Antagonists: Seizures

Question 6

The neuromodulators

Answer 6

made in a few cells with many axons such that their activation leads to widespread activity in the brain. mostly in the brainstem;

g protein in the CNS
Often diffuse short distances and so can affect neighboring cells

Classical neurotransmitters.

Question 7

Ach and norepinephrine in cns

Answer 7

casue increased attention and arousal

Question 8

seratonin

Answer 8

mood

Question 9

dopamine

Answer 9

released when unexpected good things happen and inhibited when unexpected bad happens

Question 10

What to consider when classifying neurotransmitters

Answer 10

What type of molecule is it

How/where is it made

How does it get released

what kind of receptor proteins does it bind to

How is it cleared away after use

Question 11

Classical neurotransmitter synaptic vesicle recycling

Answer 11

All classical neurotransmitters are made in axons

The parts and enzymes needed free float in the cytoplasm. When it is made, the transmitter is packed into vesicles by transporters in the membranes of the vesicles

After release, some are taken back up

Question 12

Monoamine neurotransmitters

Answer 12

Serotonin, dopamine and norepinephrine are monoamines. These are taken into vesicles by the vesicular monoamine transporter (VMAT)

This common transporter does not matter as each axon will only have one of the free floating transmitters in its cytoplasm

Question 13

Specific monoamine reuptake proteins

Answer 13

Each monoamine category has one specific reuptake protein.

Catecholamines: Serotonin, dopamine, norepjhinepherine

SERT, DAT, NET

This way a serotonin releasing axon can only reuptake serotonin which then uses the common VMAT to package this into vesicles

Question 14

Conventional neurotransmitters

Answer 14

Glutamate, GABA, dopamine, serotonin, norepinephrine, acetylcholine are locally synthesized in axon terminals
Usually secreted from vesicles (small) that dock close to the Ca2+ entry point into the cell
Active at ionotropic and metabotropic receptors in various places
Recaptured and reused
point to point diffusion
tens to hundreds of micrometers max distance

Question 15

Neuropeptides

Answer 15

eg oxytocin, vasopressin
made in soma and brought down axon
held and secreted from large dense core vesicles that dock back from the Ca2+ sit e of entry
only activate metabotropic receptors
NO synaptic recycling
May diffuse and exert action at a difference (non-synaptic communication)

Question 16

Lipid based

Answer 16

Cannaboids
synthesized and released on demand and as needed
secreted in a non vesicular manner, typically from post synaptic neurons
activate pre synaptic metabotropic receptors
modulate firing rate of pre synaptic neuron

Question 17

Black widow venom

Answer 17

causes ach release at neuromuscular junction
goes to extracellular solution
is absorbed by vesicles as they are made to recycle ach
when they dock, acts as Ca2+ and causes release
Does the same again and again
Thus Ach released without action potentials

Question 18

Botulinium

Answer 18

Ach antagonist
Extracellular solution
Stays on the vesicular membrane
Prevents Ca2+ interaction
So no Ach released despite action potentials

Question 19

Neostigmine

Answer 19

Inhibits Acetylchonenesterase activity
Causes Ach to linger for longer
Mysethemia gravis patients whos immune system attacks the Ach receptors
Get weaker with time
Cant cure it, but this makes Ach last longer so more activity