Responses of cortical EEG-related basal forebrain neurons to brainstem and sensory stimulation in...

The basal forebrain can be considered to be a rostral extension of the ascending reticular activating system. A large number of neurons in the basal forebrain have been shown to display higher firing rates when low-voltage fast activity is present in the cortical EEG as opposed to states characterized by large slow waves in both unanaesthetized and anaesthetized animals. However, a smaller number of cells with increased discharge rate during slow waves was also observed in most of these studies. While it is likely that these two types of neurons have opposite roles in the regulation of cortical activation, it is not known how they respond to inputs from the brainstem or the periphery. In the present study, extracellular recordings were made in the basal forebrain of urethane-anaesthetized rats. A total of 52 neurons were studied in which the firing rate was significantly higher during fast cortical EEG waves (F-cells), and 14 neurons in which activity was significantly greater during slow waves (S-cells). The two cell types responded differently to stimulation of the pedunculopontine tegmental nucleus (PPT) and dorsal raphe nucleus (DRN) with short (0.5-1 s) trains of pulses and to noxious sensory stimuli (tail pinch). These stimulations excited most F-cells (80-96%) and inhibited the majority of S-cells (55-67%). In the few F-cells that were inhibited by stimulation, the response varied with the background firing rate of the cell: the higher the firing rate at the time of stimulation, the higher the probability of observing an inhibitory response. In contrast, single electrical pulses delivered to the PPT and DRN excited the majority (72%) of both F- and S-cells. Previous in vitro studies have shown that the application of acetylcholine or serotonin has predominantly inhibitory effects on basal forebrain cholinergic neurons. The predominantly excitatory effect of noxious, PPT and DRN stimulation on F-cells therefore suggests that glutamatergic or other excitatory afferents play a more dominant role in regulating basal forebrain neurons. We have previously shown that F-cells are more prevalent than S-cells. In combination, these findings suggest that basal forebrain neurons, and F-cells in particular, are important in mediating the ascending excitatory drive from the brainstem to the cerebral cortex.