0158 Loss of Connexin 36 Elicits Abnormalities in Thalamocortical Network Activity Relevant to Neuropsychiatric Disorders
Sleep(2020)
摘要
Abstract Introduction Neuronal gap-junctions are extensively expressed in mammalian forebrain and suggested to contribute to state-regulation and thalamocortical network activity. However, the physiological role of gap-junctions on these processes remains poorly understood. Connexin-36 (Cxn36) is highly expressed in the brain, representing a mechanism for electrical coupling of inhibitory neurons. We examined the effects of global Cnx36 deletion on sleep/wake and spontaneous and evoked EEG activity. Methods We recorded in vivo EEG/EMG in Cxn36KO mice and littermate controls. Electrodes were stereotaxically implanted above frontal cortices. We analyzed sleep/wake states and algorithmically detected sleep spindles over 24 hours. Mice underwent auditory stimulation paradigms including the auditory steady state response (ASSR; 1 second train 20-50Hz clicks, 100 reps., 85dB) and mismatch negativity (MMN; 2.5kHz standard 90%, 10kHz deviant 10%, 300ms ISI, 90dB). Social behavior and investigation-evoked EEG activity were also assessed via the social habituation task (repeated 5 min exposures to novel mouse). Results Cnx36KO mice exhibited limited sleep/wake abnormalities (n=7/group). Power spectra of EEG revealed significant impairments in spontaneous gamma-band activity (30-80Hz; All States, Light & Dark Phases), and beta activity (15-25Hz; All States, Light Phase). Sigma activity (10-15Hz) was significantly decreased (NREM and REM, Light phase). This was particularly pronounced during NREM-REM transitions. Despite no changes in spindle density, both spindle amplitude and duration were significantly decreased in Cnx36KOs. Cxn36KOs exhibited a blunted gamma-band response to acute ketamine (15mg/kg; IP), impaired 30 & 40Hz ASSR, and an abnormal response in the MMN task (decrease ERP peak amplitude & gamma). Finally, Cxn36KO mice exhibit impaired social habituation and significantly decreased investigation evoked slow gamma-band activity (30 - 55Hz). Conclusion Our data suggest Cxn36 plays a critical role in regulating thalamocortical network activity. Further, impairments in Cnx36KO mice reflect abnormalities in neuropsychiatric disorders, including schizophrenia, implicating Cnx36 containing gap junctions as a novel therapeutic target. Support Research supported by VA CDA Award BX002130 (JMM), VA Merit Awards BX004500 (JMM), BX001404 (RB), and NIMH RO1 MH39683 (Ritchie E. Brown).
更多查看译文
关键词
thalamocortical network activity relevant,connexin,neuropsychiatric disorders,elicits abnormalities
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要