Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep

Abstract

Sleep and wakefulness are regulated primarily by inhibitory interactions between the hypothalamus and brainstem. The expression of the states of rapid eye movement (REM) sleep and non-REM (NREM) sleep also are correlated with the activity of groups of REM-off and REM-on neurons in the dorsal brainstem. However, the contribution of ventral brainstem nuclei to sleep regulation has been little characterized to date. Here we examined sleep and wakefulness in mice deficient in a homeobox transcription factor, Goosecoid-like (Gscl), which is one of the genes deleted in DiGeorge syndrome or 22q11 deletion syndrome. The expression of Gscl is restricted to the interpeduncular nucleus (IP) in the ventral region of the midbrain-hindbrain transition. The IP has reciprocal connections with several cell groups implicated in sleep/wakefulness regulation. Although Gscl −/− mice have apparently normal anatomy and connections of the IP, they exhibited a reduced total time spent in REM sleep and fewer REM sleep episodes. In addition, Gscl −/− mice showed reduced theta power during REM sleep and increased arousability during REM sleep. Gscl −/− mice also lacked the expression of DiGeorge syndrome critical region 14 (Dgcr14) in the IP. These results indicate that the absence of Gscl and Dgcr14 in the IP results in altered regulation of REM sleep.homeobox transcription factor | mouse behavior | ventral brainstem

Two major network domains in the dorsal raphe nucleus

“…The hippocampus figures prominently as a common target of the caudal DR and MR (Muzerelle et al, ), as well as their network partners. While the association of the MR, septum, and supramammillary nucleus to hippocampal theta is well established (Maru et al, ; Kocsis and Vertes, ; Vertes and Kocsis, ; Kirk and Mackay, ; Pan and McNaughton, ; Crooks et al, ), the interpeduncular nucleus, habenula, and the pathway between them are also implicated in regulating hippocampal theta (Valjakka et al, ; Funato et al, ; Aizawa et al, ; Goutagny et al, ). Taken together, these findings suggest both the caudal DR and MR contribute to networks that influence arousal and learning state, particularly under aversive conditions.…”

Forward-genetics analysis of sleep in randomly mutagenized mice

“…EEG/EMG electrode implantation was performed as described previously 34 , with isoflurane (3% for induction, 1% for maintenance) used for anesthesia. Seven days after surgery, the mice were tethered to a counterbalanced arm (Instech Laboratories) that allowed free movement and exerted minimal weight.…”

“…Hourly delta density during NREMS indicates hourly averages of delta density which is the ratio of delta power to total EEG power at each 20-second epoch. For the power spectrum of sleep/wakefulness, EEG power of each frequency bins was expressed as a percentage of the total EEG power over all frequency bins (1-30Hz) and sleep/wakefulness states 34,35 . For sleep deprivation, mice were sleep deprived for 2, 4 and 6 hours from the onset of the light phase by gently touching the cages when they started to recline and lower their heads.…”

Concordant localization of functional urotensin II and urotensin II‐related peptide binding sites in the rat brain: Atypical occurrence close to the fourth ventricle

“…The presence of UII/URP binding sites in the Sph, which sends efferent projections to IP (Olucha‐Bordonau et al, ), and to other regions involved in REM sleep control such as Hb, LDTg, PPTg, suggests that this nucleus may belong to the same neuronal network. Sph may thus participate to REM sleep regulation by the urotensinergic system, as shown for LDTg and PPTg (Haun et al, ; de Lecea and Bourgin, ; Funato et al, ).…”