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

Abstract

Extracellular electrophysiological recordings in freely moving cats have shown that serotonergic neurons from the dorsal raphe nucleus are tonically active during waking, decrease their activity during slow-wave sleep, and are nearly quiescent during paradoxical sleep. However, the mechanisms at the origin of the modulation of activity of these neurons were not identified. To fill this gap, we developed a method allowing extracellular single-unit recordings of neurons, combined with iontophoresis of agonists and antagonists in the head-restrained rat. Using this method, we were able to show that GABA is responsible for the decrease of activity of the dorsal raphe serotonergic cells both during slow-wave sleep and paradoxical sleep. In addition, combining retrograde tracing with cholera toxin B subunit and GAD immunohistochemistry, we showed that the GABAergic innervation of the dorsal raphe nucleus arises from multiple distant sources and not only from local interneurons as classically accepted. Among these afferents, we propose that GABAergic neurons located in the lateral and ventrolateral preoptic area and the pontine ventral periaqueductal gray are responsible for the reduction of activity of the serotonergic neurons of the dorsal raphe nucleus during slow-wave sleep and paradoxical sleep, respectively. © 2008 Birkhäuser Verlag AG.