Role of cholinergic system

Question 1

Examined PD patients with dementia. Assessed mental impairments by a test of memory and information

• Extensive reductions of choline acetyltransferase and less extensive reductions of acetylcholinesterase.
• Choline acetyltransferase reductions in temporal neocortex correlated with degree of mental impairment, but not with the extent of plaque or tangle formation.
• In PD but not in AD, the decrease in neocortical (esp temporal) choline acetyltransferase correlated with number of neurons in the nucleus of Meynert- susggest that primary degeneration of these cholinergic neurons may be related to declining cognitive function in PD.

Answer 1

Perry et al 1985

Question 2

Examined necroscopy brain tissue from controls and patients with depression and dementia for activities of various cholinergic components.

• Choline acetyltransferase and anticholinesterase activities decreased significantly as mean plaque count rose, and in depressed and demented subjects this correlated with the extent of intellectual impairment measured by a memory information test
• Muscarinic cholinergic receptor binding activity remained unchanged with increasing senile plaque formation but butyeylcholinesterase activity increased.
• Suggests close relationship between cholinergic system and AD.

Answer 2

Perry et al 1978

Question 3

Reported (negative) corrlation between acetylcholine synthesis and cognitive impairment in living patients with AD.

NB what does a correlation actually allow us to conclude?

Answer 3

Bowen and colleagues

Question 4

Anti-cholinergic agent scopolamine shows similar cognitive effects to those seen in ageing, when given to normal young volunteers (measured using the WAIS).

Answer 4

Drachman and Sahakian 1979

Question 5

Systematic administration of scopolamine (a muscarinic antagonist) impairs short tem memory and learning in…

NB, evidence for anti-memory consolidation effects (i.e. post-trial expeirments) is less convincing)

Answer 5

Humans- Robbins et al 1997

Monkeys- Aigner and Mishkin

Rats (Dunnett 1985)

Question 6

Assessed effect of scopolamine on visual recognition memory in rhesus monkeys with a delyed nonmatching-to-sample task employing trial-unique stimuli. Acquisition phase: 40 stimuli presented sequentially. During test phase, animal was rewarded for choosing the novel stimulus in each pair of stimuli.

Task 1) Scoppolamine administered 20 minutes prior to acquisition, which was followed immediately by test phase.

Task 2) Drug administerd immediately after acquisition, which was followed 20 mins later by the test phase

Suggests that scopolamine interferes selectively with the initial storage of the info to be remembered.

• Performance was impaired in a dose-related amanner in task 1, but not at all in task 2.
  
  • Indicates that effects of scopomamine on performance cannot be attributed to impairment in retrieval of information of in the attentive or perceptual discriminative processes needed for such retrieval, or, by implication, for storage.
• Forgetting curves for scopolamine in Task 1 were parallel to control session, i.e. curves did not diverge with increasing delay intervals – so scopolamine did not increase the rate of forgetting.

Answer 6

Aigner, Walker, Mishkin 1991 Behavioral Neural Biology