In previous experimental studies, carried out on cats, we demonstrated that electrical stimulation of lateral habenula (LH) at 0.5-3.0Hz or 5-20Hz had a double effect (low frequency-excitation; high frequency-inhibition) on the spontaneous firing rate of single hippocampal neurones. Our results, in agreement with similar case studies, allowed us to hypothesise that in the habenular modulation of the hippocampus the raphe nucleus is probably involved. In fact, all the effects of LH stimulation were antagonised by the iontophoretic intrahippocampal application of methysergide. In the present series of experiments, performed on rats, it was possible to demonstrate that LH stimulate 1-10Hz causes an excitation of a progressively major number of hippocampal neurons depending upon the increase of frequency stimulation. The absence of habenulo-induced effects after a iontophoretic application of methysergide on single hippocampal units suggests the involvement of the raphe nucleus. Furthermore, in consideration of recent anatomical evidences demonstrating an excitatory projection between LH and raphe nucleus, intraraphal N-methyl-D-aspartate (NMDA) application, performed through a Hamilton microsyringe, induces an inhibitory effect. All the results suggest that in the raphe context it is possible to hypothesise the presence of an intrinsic interneurone, directly activated by the excitatory projection arising from the LH; this interneurone is likely inhibitory on the serotonergic raphe-hippocampus efferent neurone. This functional organization is responsible for the effect of LH stimulation at different frequencies as well as for the effects of intraraphal NMDA application. effects of intraraphal NMDA application.
