Adenosinergic modulation of rat basal forebrain neurons during sleep and waking: neuronal recording with microdialysis

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Abstract
1. The cholinergic system of the basal forebrain (BF) is hypothesized to play an important role in behavioural and electrocortical arousal. Adenosine has been proposed as a sleep-promoting substance that induces sleep by inhibiting cholinergic neurons of the BF and brainstem. However, adenosinergic influences on the activity of BF neurons in naturally awake and sleeping animals have not been demonstrated. 2. We recorded the sleep-wake discharge profile of BF neurons and simultaneously assessed adenosinergic influences on wake- and sleep-related activity of these neurons by delivering adenosinergic agents adjacent to the recorded neurons with a microdialysis probe. Discharge rates of BF neurons were recorded through two to three sleep-wake episodes during baseline (artificial cerebrospinal fluid perfusion), and after delivering an adenosine transport inhibitor (s-(p-nitrobenzyl)-6-thioinosine; NBTI), or exogenous adenosine, or a selective adenosine A1 receptor antagonist (8-cyclopentyl-1, 3-dimethylxanthine; CPDX). 3. NBTI and adenosine decreased the discharge rate of BF neurons during both waking and non-rapid eye movement (NREM) sleep. In contrast, CPDX increased the discharge rate of BF neurons during both waking and NREM sleep. These results suggest that in naturally awake and sleeping animals, adenosine exerts tonic inhibitory influences on BF neurons, supporting the hypothesized role of adenosine in sleep regulation. 4. However, in the presence of exogenous adenosine, NBTI or CPDX, BF neurons retained their wake- and sleep-related discharge patterns, i.e. still exhibited changes in discharge rate during transitions between waking and NREM sleep. This suggests that other neurotransmitters/neuromodulators also contribute to the sleep-wake discharge modulation of BF neurons.