Alpha 2 adrenergic receptors on GABAergic, putative sleep-promoting basal forebrain neurons

The basal forebrain plays an important role in the modulation of cortical activity and sleep-wake states. Yet its role must be multivalent as lesions reportedly diminish cortical fast activity and also cortical slow activity along with slow wave sleep (SWS). Basal forebrain cholinergic vs. GABAergic cell groups could differentially influence these processes. By labelling recorded neurons with Neurobiotin (Nb) using the juxtacellular technique and identifying them by immunostaining, we previously found that whereas all cholinergic cells increased their firing, the majority of GABAergic neurons decreased their firing in association with evoked cortical activation in urethane-anaesthetized rats. Here, we examined the possibility that such GABAergic, cortical activation 'off' cells might bear alpha 2 adrenergic receptors (alpha2AR) through which noradrenaline (NA) could inhibit them during cortical activation. First using simple dual-immunostaining for glutamic acid decarboxylase (GAD) and the alpha2AAR, we found that the majority (approximately 60%) of GAD-immunopositive (GAD+) neurons through the magnocellular preoptic nucleus (MCPO) and substantia innominata (SI) were labelled for the alpha2AAR. Second, in urethane-anaesthetized rats, we examined whether Nb-labelled, GAD+ cortical activation 'off' neurons that discharged maximally in association with cortical slow wave activity, were immunopositive for alpha2AAR. We found that all the Nb+/GAD+'off' cells were labelled for the alpha2AAR. Such cells could be inhibited in association with cortical activation and waking when noradrenergic locus coeruleus (LC) neurons discharge and be disinhibited with cortical slow waves and SWS when these neurons become inactive. We thus propose that alpha2AR-bearing GABAergic basal forebrain neurons constitute sleep-active and sleep-promoting neurons.