5-HT 1A receptor-responsive pedunculopontine tegmental neurons suppress REM sleep and respiratory motor activity

Abstract

Serotonin type 1A (5-HT 1A) receptor-responsive neurons in the pedunculopontine tegmental nucleus (PPTn) become maximally active immediately before and during rapid eye movement (REM) sleep. A prevailing model of REM sleep generation indicates that activation of such neurons contributes significantly to the generation of REM sleep, and if correct then inactivation of such neurons ought to suppress REM sleep. We test this hypothesis using bilateral microperfusion of the 5-HT 1A receptor agonist 8-hydroxy-2-(di-npropylamino) tetralin (8-OH-DPAT, 10μM) into the PPTn; this tool has been shown to selectively silenceREMsleep-active PPTn neurons while the activity of wake/REM sleep-active PPTn neurons is unaffected. Contrary to the prevailing model, bilateral microperfusion of 8-OH-DPAT into the PPTn (n=23 rats) significantly increasedREMsleep both as a percentage of the total recording time and sleep time, compared with both within-animal vehicle controls and between-animal time-controls. This increased REM sleep resulted from an increased frequency of REM sleep bouts but not their duration, indicating an effect on mechanisms of REM sleep initiation but not maintenance. Furthermore, an increased proportion of the REM sleep bouts stemmed from periods of low REM sleep drive quantified electrographically. Targeted suppression of 5-HT 1A receptor-responsive PPTn neurons also increased respiratory rate and respiratoryrelated genioglossus activity, and increased the frequency and amplitude of the sporadic genioglossus activations occurring duringREM sleep. These data indicate that 5-HT 1A receptor-responsive PPTn neurons normally function to restrain REM sleep by elevating the drive threshold for REM sleep induction, and restrain the expression of respiratory rate and motor activities. ©2012 the authors.