Invited Symposium: Role of the Basal Forebrain Neurons in Cortical Activation and Behavioural State Regulation
We recently reported that the cholinergic region of the BF is a potent site for the sleep-inducing action of adenosine (AD). AD, a byproduct of cellular metabolism, is an inhibitory neuromodulator and putative sleep factor, previously shown in vitro to exert a tonic inhibitory control over BF and mesopontine cholinergic neurons. We propose that during prolonged wakefulness, when neural metabolism is highest, AD accumulates selectively in the BF, and promotes the transition from wakefulness to sleep by inhibiting wake-active BF neurons. We find in vivo that: 1. BF perfusion of high concentrations of either exogenous AD (300 uM), or AD transport inhibitor (doubling endogenous AD levels) reduces wakefulness in both cats and rats, a behavioral effect that is site-specific. 2. Extracellular AD in the BF is higher during wakefulness than sleep. 3. AD levels in the BF rise steadily during 6h of prolonged wakefulness, followed by a slow decline during recovery sleep, and, interestingly, this rise in BF AD during prolonged wakefulness is not observed in other sub-cortical structures. 4. Local perfusion of an A1 receptor agonist inhibits the discharge of wake-active BF neurons. Taken together these data support the hypothesis that AD, and antagonists at AD receptors, can alter behavioral state via their actions in the cholinergic zone of the BF. It remains important to determine the role of non-cholinergic wake-active BF neurons in the sleep-inducing action of AD.
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|McCarley, RW; (1998). Adenosinergic Modulation Of Basal Forebrain (BF) Neurons In The Control Of Behavioral State. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/semba/mccarley0388/index.html|
|© 1998 Author(s) Hold Copyright|