Event timing in associative learning: from biochemical reaction dynamics to behavioural observations.

Associative learning relies on event timing. Fruit flies for example, once trained with an odour that precedes electric shock, subsequently avoid this odour (punishment learning); if, on the other hand the odour follows the shock during training, it is approached later on (relief learning). During training, an odour-induced Ca(++) signal and a shock-induced dopaminergic signal converge in the Kenyon cells, synergistically activating a Ca(++)-calmodulin-sensitive adenylate cyclase, which likely leads to the synaptic plasticity underlying the conditioned avoidance of the odour. In Aplysia, the effect of serotonin on the corresponding adenylate cyclase is bi-directionally modulated by Ca(++), depending on the relative timing of the two inputs. Using a computational approach, we quantitatively explore this biochemical property of the adenylate cyclase and show that it can generate the effect of event timing on associative learning. We overcome the shortage of behavioural data in Aplysia and biochemical data in Drosophila by combining findings from both systems.