TY - JOUR
T1 - Loss of Goosecoid-like and DiGeorge syndrome critical region 14 in interpeduncular nucleus results in altered regulation of rapid eye movement sleep
AU - Funato, Hiromasa
AU - Sato, Makito
AU - Sinton, Christopher M.
AU - Gautron, Laurent
AU - Williams, S. Clay
AU - Skach, Amber
AU - Elmquist, Joel K.
AU - Skoultchi, Arthur I.
AU - Yanagisawa, Masashi
PY - 2010/10/19
Y1 - 2010/10/19
N2 - 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-hind-brain 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 REMsleep 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.
AB - 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-hind-brain 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 REMsleep 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.
KW - Homeobox transcription factor
KW - Mouse behavior
KW - Ventral brainstem
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U2 - 10.1073/pnas.1012764107
DO - 10.1073/pnas.1012764107
M3 - Article
C2 - 20921407
AN - SCOPUS:78149240061
SN - 0027-8424
VL - 107
SP - 18155
EP - 18160
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 42
ER -