Interleukin‐1β modulates state‐dependent discharge activity of preoptic area and basal forebrain neurons: role in sleep regulation

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Abstract
Interleukin‐1β (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.