Electrophysiological studies on serotonergic neurons and sleep

Abstract

When their activity is recorded extracellularly in freely moving animals, all brainstem serotonergic neurons are characterized by a typical bi- or triphasic action potential of long duration, a slow discharge activity, a decrease in spontaneous discharge rate during paradoxical sleep (PS) compared to slow-wave sleep (SWS), a depressant response to serotonergic autoreceptor agonists, and a slow conduction velocity. These unit-recording studies further demonstrate a marked heterogeneity of brainstem serotonergic neurons in general and of serotonergic dorsal raphe (DRN) neurons in particular. Serotonergic DRN neurons can be subdivided into two “typical” (types I-A and I-B) and four “atypical” (types I-C, II-A, II-B, and II-C) populations, whereas serotonergic medullary neurons can be divided into “complete” and “incomplete” types on the basis of their firing pattern during PS. “Typical” DRN neurons are evenly distributed in the DRN, and their activity is related to the level of behavioral arousal, as they discharge regularly at a high rate during waking (W) and at progressively slower rates during SWS, and cease firing during SWS with ponto-geniculo-occipital waves and PS (type I-A) or only during PS (type I-B). Serotonergic neurons in the nucleus raphe centralis superior (NCS) appear to be very much like type I-A and I-B DRN neurons in their activity across the sleep-waking cycle. In contrast, “atypical” neurons are unevenly distributed in the DRN and exhibit firing patterns distinct from those of “typical neurons”, such as a high rate of tonic activity related to motor activity (type II-A), a highest rate of tonic discharge during SWS with suppression of discharge during both W and PS (type II-B), or a sustained high or low level of tonic activity during PS (type I-C or II-C, respectively). Type II-A neurons are located in the middle portion of the DRN, type II-B in the most rostral and dorsal portion of the DRN, and types I-C and II-C in the ventral portion of the DRN near, or between, the medial longitudinal bundles. The “complete” type of serotonergic medullary neurons is evenly distributed in the medullary 5-HT cell groups, whereas the “incomplete” type is mainly located in the nucleus raphe pallidus. The suppression of discharge of type II-B DRN neurons seen during W appears to result from the activation of serotonergic autoreceptors, whereas the reduction or suppression of discharge during sleep of both typical and atypical serotonergic DRN neurons is caused by the withdrawal of excitatory drives (disfacilitation) resulting from cessation of discharge of norepinephrine, histamine and, to a lesser extent, orexin (hypocretin) (Orx/Hcrt) neurons during sleep. A similar disfacilitation mechanism appears to operate for caudal raphe neurons. These data suggest that different roles are played by brainstem serotonergic neurons in behavioral state control, functional topographic organization, and adrenergic, histaminergic, and/or orexinergic tonic control of serotonergic neurons during wake-sleep states.