Fadda et al. (1996)

Effect of the neurotransmitter acetylcholine on the memory of rats.

Aim: To examine whether food-reinforced alternation performance in a T-maze was associated with increased acetylcholine output in the dorsal hippocampus in rats, in anticipation, activity and memory. (Note: The researchers use the term “cholinergic projection system” in the original article. A cholinergic neuron is a nerve cell that mainly uses the neurotransmitter acetylcholine (ACh) to send its messages. The cholinergic projection system refers to these neurons and their projections – “sticking-out bits” – in the basal forebrain of mammals).

Method: The experimental rats were given unlimited access to water, but deprived of food for 23 hours out of 24, to make them hungry and at 80% of their body weight. They were then trained using a T-maze. The rats were trained to make 12 consecutive trials (one session) in which they had to alternate between the right and left arms of the maze to obtain a shelled sunflower seed. On the first trial of each session, access to one of the arms was blocked, forcing the rat to enter only the opposite arm. On each of the next 11 trials the food was placed in the arm opposite to that in the previous trial and both arms were unblocked (free-choice trials). A correct trial ended with the rat eating the food. An incorrect trial ended with the rat reaching the empty food cup.

The rats were trained for 12-15 days, until they reached at least nine successful trials out of 11 for three consecutive sessions. Control rats were introduced into the T-maze only on the day of the experiment, but were handled in the same way and for the same time as trained rats. Acetylcholine in the rats’ brains was measured by use of a specially implanted probe.

All of the rats were placed in a waiting cage for 20 minutes before the experiment, and returned to their home cage after the experiment. ACh was measured before, during and up to 30 minutes after the experiment.

Results: 1) There was an increase in ACh in the hippocampi of the trained rats before the task, but not in the control rats. This shows that ACh increases with anticipation of a learning task.

2) There was an increase in ACh in the hippocampi of the control group rats during the first 10 minutes of the task, after which it decreased back to the basal level and stayed there.

3) The ACh stayed high throughout the task for the trained rats, and decreased slowly after the task.

Conclusion: Acetylcholine release in the hippocampus increases during anticipation and when rats are performing the task, suggesting that cholinergic activity is important in processes of arousal, attention and memory. Furthermore the data support previous findings that the cholinergic system plays a major role in memory, particularly in spatial memory.

Evaluation:

Can these results be applied to humans? Gais and Born (2004) showed that acetylcholine is important in declarative memory, with low levels being vital during slow-wave sleep (SWS) for the consolidation of memories. Increasing cholinergic activity during SWS resulted in a loss of declarative memories, but no effect on procedural (e.g. spatial) memories. While not directly arisen from the Fadda et al research, this does show the complex relationship between acetylcholine and memory.

The degeneration of acetylcholine-releasing neurons has long been associated with Alzheimer’s disease.

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