Experimental evidence has implicated the hypothalamic-basal forebrain (BF) area in the control of sleep-walking cycles. Various stimulation methods applied to this area can promote sleep, and BF ablations suppress sleep. Recent anatomical evidence demonstrates that the BF is the source of a widespread monosynaptic projection to neocortical and limbic sites, that this projection is reciprocal, and that corticopetal BF cell groups also have connections with brainstem areas implicated in the control of arousal. Thus, neurons within the BF are ideally situated to modulate changes in cortical excitability associated with changing sleep-walking state. Experiments will examine the state-related neurophysiology of neurons in various hypothalamic-BF subregions, focusing on areas implicated in the control of sleep by previous physiological experiments, or by anatomical considerations. A subpopulation of BF neurons exhibits a unique sleep-active discharge pattern,i.e., these neurons are maximally active during sleep and drowsiness, and nearly silent during waking. They have been recorded only in or near the richly cholinergic magnocellular BF nuclei. Sleep-walking discharge profiles will be mapped throughout the BF to determine if this unique cell type is confined to the magnocellular nuclei. In addition, the synaptic connectivity of recorded cells will be examined using neurophysiological techniques, to determine if sleep-wake discharge profiles are correlated with afferant or efferent projection patterns. The ability of BF neurons to encode increased sleep propensity associated with sleep deprivation will also be determined. A second series of experiments will examine the effects on sleep and on the frequency composition of cortical EEG of BF cell loss produced by microinjections of ibotenic acid, a neurotoxin which destroys cell bodies while sparing fibers of passage. Preliminary results indicate that neurotoxin lesion of the rostral magnocellular nuclei cause suppression of deep slow-wave sleep and REM sleep, and reductions in EEG spindling during sleep. The effects of cell loss in various BF subregions will be compared, and changes in neocortical neurochemical markers associated with BF damage will also be determined. BF neurons are lost in number of degenerative diseases of aging. Knowledge of BF sleep mechanisms will facilitate understanding of sleep and EEG abnormalities accompanying these diseases.
| Szymusiak, R; Danowski, J; McGinty, D (1991) Exposure to heat restores sleep in cats with preoptic/anterior hypothalamic cell loss. Brain Res 541:134-8 |
| Szymusiak, R; McGinty, D; Shouse, M N et al. (1990) Effects of systemic atropine sulfate administration on the frequency content of the cat sensorimotor EEG during sleep and waking. Behav Neurosci 104:217-25 |
| Szymusiak, R; Iriye, T; McGinty, D (1989) Sleep-waking discharge of neurons in the posterior lateral hypothalamic area of cats. Brain Res Bull 23:111-20 |
| Szymusiak, R; McGinty, D (1989) Effects of basal forebrain stimulation on the waking discharge of neurons in the midbrain reticular formation of cats. Brain Res 498:355-9 |
| Szymusiak, R; McGinty, D (1989) Sleep-waking discharge of basal forebrain projection neurons in cats. Brain Res Bull 22:423-30 |
