cholinergic systems

Question 1

What are the 6 cholinergic nuclei?

Answer 1

CH1 - medial septal nuclei
CH2 - vertical band of Broca
CH3 - horizontal band of Broca
CH4 - Basal nucelus of Meynert
CH5 - pedunculopontine
CH6 - lateral dorsal tegmentum

CH1-4 - basal forebrain
CH5-6 - mesopontine tegmentum

Question 2

Which neuromodulators are transmitted in the basal forebrain?

Answer 2

Acetylcholine (cholinergic), GABA (GABAergic), glutamate (glutamatergic)

Question 3

Which basal forebrain nuceli are cholinergic?

Answer 3

CH1 - consists of 10 - 20% cholinergic
CH2 - 70% cholinergic
CH4 - 90% cholinergic (least heterogenous nuclei)

Question 4

Where does CH1 and CH2 project to?

Answer 4

Hippocampus (via fornix), PFC, hypothalamus (orexin neurons)

Question 5

Where does CH3 project to?

Answer 5

Olfactory bulb

Question 6

Where does CH4 a and b project to?

Answer 6

CH4a to basolateral amygdala
CH4b to cortex

Question 7

What is the function of the basal forebrain?

Answer 7

Integrative hub of descending sensory and motor information, which conveys information to the limbic system.
The basal forebrain is also involved in the default mode network (CH1 and 2) and attentional mode network (CH4)

Question 8

Why are cholinergic neurons highly susceptible to damage?

Answer 8

They have a small cell body and long axons susceptible to damage.

Question 9

How do cholinergic neurons act?

Answer 9

Acts by releasing acetylcholine on to neurons via synaptic or volume transmission. It works on muscarinic receptors, which are excitatory and inhibitory, and nicotinic receptors, which are only excitatory but exists on excitatory and inhibitory neurons.

Question 10

What are the thee genes required for synthesis and release of acetylcholine?

Answer 10

cholinetgic acetyl transferase (ChAT), vesicular acetycholine transporter (VaChT) and the choline transporter 1.

Question 11

What is the cholinergic regulation of attention?

Answer 11

Cholinergic regulation of attention ensures that the brain pays less attention to irrelevant stimuli and more attention to salient/ novel stimuli. When a cue is sounded, ACh is released, resetting the brain’s oscillation and dampening overall signals. When novel stimuli is detected, glutamate is released -> the dampening of signals by ACh leads to a heightened glutamatergic responses. ACh also disinhibits neurons inhibiting glutamate, resulting in heightened glutamatergis transmission. This occurs in shock/ fear training, wherein the basal forebrain ties the two stimuli together

Question 12

How do we determine the function of cholinergic basal forebrain neurons?

Answer 12

lesions studies
manipulate cell number or connections
record from them

Question 13

What chemical can be used to lesion the BF?

Answer 13

Alpha P75 saporin -> stops cholinergic cells from replicating, causes lesions

Question 14

What is allocentric/ allothetic and egocentric/ idothetic navigation?

Answer 14

Allocentric - landmark dependent, memory of the environment. Uses hippocampus and place cells, does not require integration
Egocentric - your position in relation to the environment. Uses PFC and sensory integration

Question 15

What form of navigation is tested using the Morris Water maze? What was the primary finding about the BF in this study?

Answer 15

Allocentric/ allothetic navigation -> when the BF was lesioned (connection to hippocampus severed), the mice initially performed no differently on the water maze. However, when the maze was changed so the mice had to update their memory, they struggled, and saw no improvement across trials

Question 16

What test is used to test egocentric/ idothetic navigation?

Answer 16

Foot shock avoidance task -> mice with BF lesions showed disorganised behaviour, returning to the foot shock section several times - clearly have a memory of the area, however they are struggling to integrate that memory and sensory input and adjust their behaviour accordingly

Question 17

What are three other areas important for navigation?

Answer 17

Posterior parietal cortex (body position information), restrosplenial cortex (facilitates translating between allocentric and egocentric perspectives), prefrontal cortex (important for route planning).

Question 18

Why is verbal fluency a good test of cholinergic ability?

Answer 18

It requires action of mutliple cognitive processes -> engages verbal knowledge, executive functions and memory

Question 19

What are the cognitive symptoms of Alzheimers disease?

Answer 19

Need to have deficits in atleast 2 of:
- memory
- language
- attention
- executive functions
- visuospatial abilities

-> basal forebrain plays a role in atleast two of these functions

Question 20

What are the three things needed to be diagnosed with alzheimers?

Answer 20

amyloid plaques, tau fibrillary tangles, neuronal and synaptic degeneration

Question 21

What causes a build up of amyloid in the brain?

Answer 21

The underclearingo famyloid leads to amyloid build up, wherein it condenses in to oligomers
Genetic basis - people with APP, PSEN1 and PSEN2 mutations will overproduce amyloid

Question 22

How does sporadic Alzheimers occur?

Answer 22

You might get a change in the way you slice amyloid precurser protein, leading to an increased production of beta-amyloid

Question 23

What results do we see in the human morris water maze?

Answer 23

In the human morris water maze, we see difficulties in both allo and ego centric navigation in early dementia

Question 24

What are the issues with current Alzheimers treatments?

Answer 24

Current treatments are acetylcholine esterase inhibitors. Breaking all the esterase will provide an overall increase in active ACh across the brain, throwing off the timing of ACh transmission. Cholinergic neurons are also destroyed in Alzheimers, so giving esterase inhibitors may not do anything bc they do not have anything to bind to. The drugs are also not given at a high enough dose, as a high dose causes extreme side effects.