ABSTRACT

Since discovery in 1998 of the hypothalamic neuropeptide hypocretin (Hcrt), also known as orexin, the study of Hcrt behavioral function has mainly been carried out by using of cFos immunostaining. It has been found increased c-Fos expression during locomotion, active wakefulness and decreased number of c-Fos positive Hcrt neurons during quite wakefulness and even more so during NREM sleep. Results have been controversial for rapid eye movement (REM) sleep. This method has a number of important limitations, in particular insufficient temporal resolution and dissociation of c-Fos expression and neuronal firing (1,2). A number of major questions that cannot be addressed using cFos also still need to be addressed. First, what is the baseline activity of Hcrt neurons in the brain during wakefulness? Second, why does such small portion of entire Hcrt population show c-Fos expression in response on variety of behavioral challenges? Third, why does the medial part of Hcrt cell field express c-Fos more readily than the lateral portion? Finally, what is the activity of these cells during REM sleep, whether tonic or phasic.