Sleep suppression following kainic acid-induced lesions of the basal forebrain.

We have described elsewhere neurons in the ventral basal forebrain of cats that have elevated discharge rates during sleep and during transitions from waking to sleep, yet have comparatively low discharge rates during waking. These sleep-active neurons may mediate the hypnogenic properties of the basal forebrain. To further evaluate their role in the control of sleep, we examined the effects of basal forebrain lesions produced by microinjections of the relatively cell-selective neurotoxin, kainic acid, on sleep. Lesions were made bilaterally in two regions that contain high densities of sleep-active neurons: the horizontal limb of the diagonal bands of Broca and the lateral preoptic area-substantia innominata. Twelve-hour polygraph recordings were made before and at various intervals after basal forebrain damage in a total of eight cats. The lesions resulted in reduced time spent in deep, nonrapid eye-movement sleep and REM sleep, and increased time spent awake. These abnormalities persisted through 6 to 7 weeks postlesion. Reductions in deep non-REM sleep were due to decreases in bout number, particularly in the number of extended deep non-REM episodes (i.e., those greater than 5 min in duration). The number of REM sleep episodes was also significantly reduced. The average duration of epochs of waking was elevated throughout the postlesion period. Thus, in the postlesion period, cats exhibited an impaired ability to initiate and maintain consolidated periods of sleep, particularly of deeper sleep stages. Lesions were also associated with reduced EEG spindling during sleep. These results are consistent with our hypothesis that sleep-active neurons are a component of a basal forebrain sleep- and EEG-regulating mechanism.