HIPPOCAMPAL ACETYLCHOLINE AND HABITUATION LEARNING

Acetylcholine neurotransmission is considered to play a critical role in processes underlying behavioural activity, arousal, attention, lear ning, and memory. These functional attributions have largely been base d 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 recen tly become possible to monitor acetylcholine in the brain of the behav ing animal, which allows to investigate its activity in specific behav ioural tasks. With respect to learning and memory, one of the most ele mentary experimental paradigms is that of behavioural habituation, whe re the decrease of exploratory activity as a function of repeated expo sure to the same environment is taken as an index of memory. We have u sed 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 eac h). The results show that exposure of rats to the novel environment le d to increased extracellular levels of hippocampal acetylcholine which were positively correlated with exploratory behaviour. These choliner gic activations were larger than those of control animals which were h andled like the experimental animals but which were not exposed to the open held. When re-exposing the experimental animals to the same envi ronment, exploratory behaviour, but not cholinergic activation, was de creased, indicating habituation. In the subsequent 10 min, that is, wh en the animals where back in their home cages, cholinergic activity wa s still increased. The magnitude of increase was larger after re-expos ure than after exposure to the novel open field. Finally, we different iated the animals into ''superior'' vs ''inferior'' learners and found that the ''superior'' learners showed higher behavioural activation i n 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 hab ituation. Furthermore, an interindividual variability of cholinergic a ctivation seems to exist which is related to individual differences in behavioural responsiveness to novelty. Such differences in cholinergi c activity may be related to other known differences in hippocampal st ructure and function and may be important for previously reported inte r-individual variabilities in sensation-seeking and related mnestic fu nctions. (C) 1998 IBRO. Published by Elsevier Science Ltd.