Nicotinic receptors in the habenula: importance for memory

The habenula is an epithalamic structure through which descending connections pass from the telencephalon to the brainstem, putting it in a key location to provide feedback control over the brainstem monoaminergic projections ascending to the telencephalon. Habenular nuclei lesions have been shown to impair memory function. The habenular nuclei have high concentrations of nicotinic receptors. In this study we assessed the role of habenular nicotinic receptors for working memory. Adult female Sprague–Dawley rats were trained on a 16-arm maze to assess spatial working and reference memory. All rats had at least 18 sessions of training and then had bilateral chronic infusion cannulae placed into the lateral habenula nucleus. These cannulae were each connected to a slow delivery osmotic minipump that chronically infused mecamylamine 100 μg/side/day (n=9) or vehicle (aCSF) for controls (n=15) for a period of 4 weeks. Both mecamylamine-infused and control rats were acutely injected (s.c.) with nicotine (0, 0.2 or 0.4 mg/kg) in a repeated measures counterbalanced design twice at each dose during the chronic local infusion period. There was a significant (P<0.025) mecamylamine×nicotine interaction effect on memory performance. Without nicotine injection the chronic habenular mecamylamine infusion caused a significant (P<0.05) increase in total memory errors. The 0.4 mg/kg nicotine dose significantly (P<0.005) reversed the mecamylamine-induced memory impairment, returning performance back to levels seen in rats with control aCSF habenular infusions. The current study determined that nicotinic receptors in the lateral habenular nucleus are important for spatial memory function. Descending projections from the telencephalon through the habenula to brainstem nuclei using nicotinic receptors appear to be a key pathway for memory processing.