In:
Journal of Neurochemistry, Wiley, Vol. 136, No. 3 ( 2016-02), p. 609-619
Abstract:
The Ca 2+ modulation in the dorsal raphe nucleus ( DRN ) plays an important role in sleep–wake regulation. Calmodulin‐dependent kinase II (Ca MKII ) is an important signal‐transducing molecule that is activated by Ca 2+ . This study investigated the effects of intracellular Ca 2+ /Ca MKII signaling in the DRN on sleep–wake states in rats. Maximum and minimum Ca MKII phosphorylation was detected at Zeitgeber time 21 ( ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light–dark rhythm in the DRN in rats. Six‐hour sleep deprivation significantly reduced Ca MKII phosphorylation in the DRN . Microinjection of the CAMKII activation inhibitor KN ‐93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid‐eye‐movement sleep ( REMS ) and non‐ REM sleep ( NREMS ). Application of a high dose of KN ‐93 (10 nmol) increased slow‐wave sleep ( SWS ) time, SWS bouts, the mean duration of SWS , the percentage of SWS relative to total sleep, and delta power density during NREMS . Microinjection of CaCl 2 (50 nmol) in the DRN increased Ca MKII phosphorylation and decreased NREMS , SWS , and REMS . KN ‐93 abolished the inhibitory effects of CaCl 2 on NREMS , SWS , and REMS . These data indicate a novel wake‐promoting and sleep‐suppressing role for the Ca 2+ /Ca MKII signaling pathway in DRN neurons. image We propose that the intracellular Ca 2+ /Ca MKII signaling in the dorsal raphe nucleus ( DRN ) plays wake‐promoting and sleep‐suppressing role in rats. Intra‐ DRN application of KN ‐93 (Ca MKII activation inhibitor) suppressed wakefulness and enhanced rapid‐eye‐movement sleep ( REMS ) and non‐ REMS ( NREMS ). Intra‐ DRN application of CaCl 2 attenuated REMS and NREMS . We think these findings should provide a novel cellular and molecular mechanism of sleep–wake regulation.
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2016.136.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
80158-6
detail.hit.zdb_id:
2020528-4
SSG:
12
