Lecture 11: Modulation of Neuronal Function by Metabotropic Receptors

Question 1

Function and location of dopamine neuromodulatory system

Answer 1

Midbrain - movement (especially initiation)

Question 2

Function and location of acetylcholine neuromodulatory systems.

Answer 2

Pons - sleep and wakefulness

Forebrain - learning, memory, attention

Question 3

Function and location of serotonin neuromodulatory system:

Answer 3

Serotonin raphe nuclei located in the medulla, pons and midbrain.
Regulates appetite, libido, sleep, mood, pain

Question 4

Function and location of noradrenaline neuromodulatory system

Answer 4

Located in the pons, regulates mood, vigilance, pain

Question 5

The reticular activation system consists of:

Answer 5

The serotoninergic raphe nuclei
The cholinergic system of the pons
The noradrenergic locus coeruleus

Question 6

The function and location of the reticular activation system

Answer 6

Located in the brain stem (pons), this system controls sleep wake cycles (including REM), arousal and vigilance

Question 7

Function of the Cholinergic Neuromodulatory System in the Basal Forebrain

Answer 7

Consists of several contiguous groups (nuclei) of magnocellular cholinergic neurons. From rostral to caudal, these are: septum, diagonal band (of Broca), basal nucleus (of Meynert).
Regulate hippocampus function - involved in episodic memory

Question 8

The axons of the septal cholinergic neurons traverse via a bundle of axons known as ___ to innervate the hippocampus

Answer 8

Fornix

Question 9

The axons of which group of cholinergic neurons innervate the hippocampus.

Answer 9

The septum

Question 10

Function of the septo-hippocampal system

Answer 10

It is crucial for long-term memory formation

Question 11

True or false:
Evolutionary, septum and hippocampus originated from spatially similar regions but grew apart with the development of the cerebral cortex.

Answer 11

True.

Question 12

Function of muscarinic acetylcholine receptor M2

Answer 12

M2 muscarinic receptors act via a Gi type receptor (Gi alpha subunit inhibits the production of cAMP from ATP. Gαi = Adenylate Cyclase inhibitor). This causes a decrease in cAMP in the cell, generally leading to inhibitory-type effects. They appear to serve as autoreceptors.
In addition, they modulate muscarinic potassium channels.
In the heart, this contributes to a decreased heart rate. They do so by the G beta gamma subunit of the G protein coupled to M2. This part of the G protein can open K+ channels in the parasympathetic notches in the heart, which causes an outward current of potassium, which slows down the heart rate.

Question 13

Function of muscarinic acetylcholine receptor M1

Answer 13

This receptor is found mediating slow EPSP at the ganglion in the postganglionic nerve.
It is predominantly found bound to G proteins of class Gq which activates phospholipase C.

Question 14

M1, M3, M5 receptors activate…

Answer 14

M1, M3, M5 activate phospholipase C. Therefore induce:
↑ IP3
↑ Ca++
↑ excitability of pyramidal neurons

Question 15

M2, M4 inhibit…

Answer 15

M2, M4 — inhibit adenylyl cyclase.
↓ cAMP
↓ excitability (post-synaptic)
↓ release (pre-synaptic)

Question 16

Activation of M1 type muscarinic receptors in hippocampus leads to…

Answer 16

Activation of phospholipase C, therefore ↑ IP3, ↑ Ca++, ↑ excitability of pyramidal neurons.
Closure of M-type K+ channels (not involved with action potential) (βγ) - depolarising/excitatory effect.

Question 17

True or false:

Most cholinergic release sites in the neocortex are not synaptic.

Answer 17

True. 90% of cholinergic release sites in the neocortex and hippocampus are not synaptic
Instead, ACh is released from varicosities, into the ECF
Cholinergic axons form many branches in the target tissue, and each branch has varicosities spaced about 2.5 microns apart
Each cholinergic neuron has between 200,000 and 500,000 release sites.

Question 18

True or false:

Each cholinergic neuron has 1 release site.

Answer 18

False. Each cholinergic neuron has between 200,000 and 500,000 release sites.

Question 19

Release of ACh onto CA1 pyramidal cells causes

Answer 19

slight depolarisation of the pyramidal cell but more importantly allows the pyramidal cell to fire at high frequency

Question 20

Cutting of the fornix results in…

Answer 20

Decreased function of the hippocampal pyramidal cells and atrophy and possible cell death of the cholinergic neurons