Role of the lateral habenula in shaping context-dependent locomotor activity during cognitive tasks.

Lesions of the lateral habenula are accompanied by cognitive and emotional deficits. Here we examine how the two sets of deficit may be correlated. In the forced swimming test, control rats had reduced motility and showed a depression-like behavior, as expected. In contrast, rats with bilateral lesions of the lateral habenula presented (on day 2) an increased motility over that of the controls, which suggested the presence of hyperactivity and antidepression effect. In addition, the spontaneous activity of the lesioned rats was elevated. We then examined the cognitive deficits in these hyperactive rats. In the contextual fear conditioning, the habenula-lesioned rats did not show the expected freezing and remained hyperactive. In the Morris water maze test, the lesioned rats performed poorly while showing a decreased motor activity. In the active avoidance test, there was no difference in the rate of avoidance between operated and control rats; however, once they failed to change compartments upon the cue, the operated rats tended to remain in the same compartment as under shock, thus showing hypoactivity. In summary, in the lesioned animals the hyperactivity that counteracts the depression-like effect is persistent or inadequately modified in the course of cognitive tasks. We suggest that the lateral habenula is required for regulating emotional influences on locomotor activity, so that the animal's behavior is singularly adapted to different cognitive tasks.