Lateral habenula and hippocampus: a complex interaction raphe cells-mediated

The study has shown an excitatory influence exerted by lateral habenula (LH) on hippocampal pyramidal cells. The modulatory influence is paradoxically serotonine-mediated; in fact all LH stimulation effects were abolished by intrahippocampal iontophoretic methysergide application. The data suggest the involvement of dorsal raphe nucleus. In fact, the dorsal raphe nucleus stimulation caused on hippocampus an expected inhibitory effect antagonized by intrahippocampal iontophoretic methysergide application. In the context of this neural structure we have highlighted a disinhibitory relation between two types of cells: slow serotonergic efferent neurones and fast GABAergic interneurones. The disinhibitory hypothesis is also supported by the following experimental tests performed on both slow and fast raphe cells: a) LH stimulation at low and high frequencies; b) iontophoretic administration of NMDA and GABA; c) LH stimulation during intraraphe iontophoretic injection of 2-APV (NMDA antagonist) and bicuculline (GABA antagonist).