Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons

Extracellular electrophysiological recordings in freely moving cats have sh own that serotonergic neurons from the dorsal raphe nucleus (DRN) fire toni cally during wakefulness, decrease their activity during slow wave sleep (S WS), and are nearly quiescent during paradoxical sleep (PS). The mechanisms at the origin of the modulation of activity of these neurons are still unk nown. Here, we show in the unanesthetized rat that the iontophoretic applic ation of the GABA(A) antagonist bicuculline on dorsal raphe serotonergic ne urons induces a tonic discharge during SWS and PS and an increase of discha rge rate during quiet waking. These data strongly suggest that an increase of a GABAergic inhibitory tone present during wakefulness is responsible fo r the decrease of activity of the dorsal raphe serotonergic cells during sl ow wave and paradoxical sleep. In addition, by combining retrograde tracing with cholera toxin B subunit and glutamic acid decarboxylase immunohistoch emistry, we demonstrate that the GABAergic innervation of the dorsal raphe nucleus arises from multiple distant sources and not only from interneurons as classically accepted. Among these afferents, GABAergic neurons located in the lateral preoptic area and the pontine ventral periaqueductal gray in cluding the DRN itself could be responsible for the reduction of activity o f the serotonergic neurons of the dorsal raphe nucleus during slow wave and paradoxical sleep, respectively.