A CORTICAL NEUROPEPTIDE WITH NEURONAL DEPRESSANT AND SLEEP-MODULATINGPROPERTIES

ACETYLCHOLINE (ACh) plays a key role in the transitions between the di fferent phases of sleep(1): Slow-wave sleep requires low ACh concentra tions in the brain, whereas rapid-eye-movement (REM) sleep is associat ed with high levels of ACh, Also, these phases of sleep are differenti ally sensitive to a number of endogenous neuropeptides and cytokines, including somatostatin, which has been shown to increase REM sleep wit hout significantly affecting other phases(2). Here we report the cloni ng and initial characterization of cortistatin, a neuropeptide that ex hibits strong structural similarity to somatostatin, although it is th e product of a different gene. Administration of cortistatin depresses neuronal electrical activity but, unlike somatostatin, induces low-fr equency waves in the cerebral cortex and antagonizes the effects of ac etylcholine on hippocampal and cortical measures of excitability. This suggests a mechanism for cortical synchronization related to sleep.