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

1. The cholinergic system of the basal forebrain (BF) is hypothesized to pl ay an important role in behavioural and electrocortical arousal. Adenosine has been proposed as a sleep-promoting substance that induces sleep by inhi biting cholinergic neurons of the BF and brainstem. However, adenosinergic influences on the activity of BF neurons in naturally awake and sleeping an imals have not been demonstrated. 2. We recorded the sleep-make discharge profile of BF neurons and simultane ously assessed adenosinergic influences on wake- and sleep-related activity of these neurons by delivering adenosinergic agents adjacent to the record ed neurons with a microdialysis probe. Discharge rates of BF neurons were r ecorded through two to three sleep-wake episodes during baseline (artificia l cerebrospinal fluid perfusion), and after delivering an adenosine transpo rt inhibitor (s-(p-nitrobenzyl)-6-thioinosine; NBTI), or exogenous adenosin e, or a selective adenosine A1. receptor antagonist (8-cyclopentyl-1,3-dime thylxanthine; CPDX). 3. NBTI and adenosine decreased the discharge rate of BF neurons during bot h waking and non-rapid eye movement (NREM) sleep. In contrast, CPDX increas ed the discharge rate of BF neurons during both waking and NREM sleep. Thes e results suggest that in naturally awake and sleeping animals, adenosine e xerts tonic inhibitory influences on BF neurons, supporting the hypothesize d role of adenosine in sleep regulation. 4. However, in the presence of exogenous adenosine, NBTI or CPDX, BF neuron s retained their wake- and sleep-related discharge patterns, i.e. still exh ibited changes in discharge rate during transitions between waking and NREM sleep. This suggests that other neuro transmitters/neuromodulators also co ntribute to the sleep-wake discharge modulation of BF neurons.