Learning-dependent activation of Fra-1: involvement of ventral hippocampus and SNc/VTA complex in learning and habit formation.

Although the effect of overtraining on learning processes in rats has long been studied, only few studies have specifically assessed the differential involvement of brain areas in habit formation. We used the analysis of expression of the immediate early gene Fra-1 as a tool to differentiate the areas involved in training and overtraining. Behavioural experiments showed that instrumental performance (signalled and non-signalled instrumental tasks), but not pavlovian conditioned responses, were no longer under the control of the incentive value of the reward after overtraining. The number of Fra-1 expressing neurons was increased in SNc/VTA and ventral hippocampus after training in all groups independently of behavioural performance. After overtraining, the number of learning-induced Fra-1 immunoreactive neurons remained increased in the SNc/VTA. However, in CA1, it significantly decreased in the signalled instrumental group, whereas it further increased in the pavlovian group, with no modulation in non-signalled instrumental animals. The increase in the number of Fra-1 neurons observed after training in SNc/VTA and ventral hippocampus suggests that a general underlying incentive process regulates Fra-1. Moreover, the sustained increased expression of Fra-1 in the SNc/VTA after instrumental overtraining could reflect a possible role of dopaminergic neurons in habit formation.