Hippocampal acetylcholine and habituation learning.

Acetylcholine neurotransmission is considered to play a critical role in processes underlying behavioural activity, arousal, attention, learning, and memory. These functional attributions have largely been based on pharmacological findings. or data from brain damaged animals, and humans with neurodegenerative diseases, such as Alzheimer's disease. With the introduction of the in vivo microdialysis method it has recently become possible to monitor acetylcholine in the brain of the behaving animal, which allows to investigate its activity in specific behavioural tasks. With respect to learning and memory, one of the most elementary experimental paradigms is that of behavioural habituation, where the decrease of exploratory activity as a function of repeated exposure to the same environment is taken as an index of memory. We have used this paradigm to monitor hippocampal acetylcholine levels by means of in vivo microdialysis in rats, which were exposed to a novel open field and which were re-exposed to it on the following day (10 min each). The results show that exposure of rats to the novel environment led to increased extracellular levels of hippocampal acetylcholine which were positively correlated with exploratory behaviour. These cholinergic activations were larger than those of control animals which were handled like the experimental animals but which were not exposed to the open field. When re-exposing the experimental animals to the same environment, exploratory behaviour, but not cholinergic activation, was decreased. indicating habituation. In the subsequent 10 min, that is, when the animals where back in their home cages, cholinergic activity was still increased. The magnitude of increase was larger after re-exposure than after exposure to the novel open field. Finally, we differentiated the animals into "superior" vs "inferior" learners and found that the "superior" learners showed higher behavioural activation in the novel environment and stronger neurochemical responses, both. in the novel and familiar environment. Our data show that extracellular levels of hippocampal acetylcholine are not only elevated in relation to novelty and behavioural activation. but also during behavioural habituation. Furthermore, an inter-individual variability of cholinergic activation seems to exist which is related to individual differences in behavioural responsiveness to novelty. Such differences in cholinergic activity may be related to other known differences in hippocampal structure and function and may be important for previously reported inter-individual variabilities in sensation-seeking and related mnestic functions.