Interleukin-1beta modulates state-dependent discharge activity of preoptic area and basal forebrain neurons: role in sleep regulation.

ABSTRACT

Interleukin-1beta (IL-1) is a pro-inflammatory cytokine that has been implicated in the regulation of nonrapid eye movement (nonREM) sleep. IL-1, IL-1 receptors and the IL-1 receptor antagonist (ra) are present normally in discrete brain regions, including the preoptic area (POA) of the hypothalamus and the adjoining magnocellular basal forebrain (BF). The POA/BF have been implicated in the regulation of sleep-wakefulness. We hypothesized that IL-1 promotes nonREM sleep, in part by altering the state-dependent discharge activity of POA/BF neurons. We recorded the sleep-wake discharge profiles of 83 neurons in the lateral POA/BF and assessed the effects of IL-1, IL-1ra, and IL-ra + IL-1 delivered through a microdialysis probe on state-dependent neuronal discharge activity. IL-1 decreased the discharge rate of POA/BF neurons as a group (n = 55) but wake-related and sleep-related neurons responded differently. IL-1 significantly decreased the discharge rate of wake-related neurons. Of 24 wake-related neurons studied, 19 (79%) neurons exhibited a greater than 20% change in their discharge in the presence of IL-1 during waking. IL-1 suppressed the discharge activity of 18 of 19 responsive neurons. Of 13 sleep-related neurons studied, IL-1 increased the discharge activity of five and suppressed the discharge activity of four neurons. IL-1ra increased the discharge activity of four of nine neurons and significantly attenuated IL-1-induced effects on neuronal activity of POA/BF neurons (n = 19). These results suggest that the sleep-promoting effects of IL-1 may be mediated, in part, via the suppression of wake-related neurons and the activation of a subpopulation of sleep-related neurons in the POA/BF.