Effects of hypocretin-1 in 192-IgG-saporin-lesioned rats.

Hypocretin, also known as orexin, is a neuropeptide located in the perifornical region of the lateral hypothalamus; this region projects to all the major arousal centres including the basal forebrain. The basal forebrain contains a mixed population of neurons, some of which are cholinergic. To identify the relative contribution of the noncholinergic neurons to arousal, here we utilized 192-IgG-saporin to lesion the basal forebrain cholinergic neurons and determine whether microinjection of hypocretin-1 to the basal forebrain is still effective in inducing arousal.

Adenosine and sleep homeostasis in the Basal forebrain.

It is currently hypothesized that the drive to sleep is determined by the activity of the basal forebrain (BF) cholinergic neurons, which release adenosine (AD), perhaps because of increased metabolic activity associated with the neuronal discharge during waking, and the accumulating AD begins to inhibit these neurons so that sleep-active neurons can become active. This hypothesis grew from the observation that AD induces sleep and AD levels increase with wake in the basal forebrain, but surprisingly it still remains untested. Here we directly test whether the basal forebrain cholinergic neurons are central to the AD regulation of sleep drive by administering 192-IgG-saporin to lesion the BF cholinergic neurons and then measuring AD levels in the BF.