Unilateral cortical application of interleukin-1β (IL1β) induces asymmetry in fos, IL1β and nerve growth factor immunoreactivity: Implications for sleep regulation

Abstract

Unilateral injection of interleukin-1 beta (IL1β) into the somatosensory cortex enhances EEG slow wave activity ipsilaterally during non-rapid eye movement sleep [Yasuda, T., Yoshida, H., Garcia-Garcia, F., Kay, D., Krueger, J.M., 2005. Interleukin-1β has a role in cerebral cortical state-dependent electroencephalographic slow-wave activity. Sleep 28, 177-184]. We show that a similar unilateral microinjection of IL1β (10 ng) into layer VI or onto the surface of the primary somatosensory cortex induced increases in the neuronal activity marker, Fos, relative to the contralateral side that received saline or heat-inactivated IL1β. When IL1β was microinjected into layer VI, increases in Fos-immunoreactive nuclei were evident in layers II, III and VI of the somatosensory cortex and connected cortical regions, such as the endopiriform, secondary somatosensory, piriform and prefrontal cortex. Asymmetrical increases in Fos were also observed in subcortical regions, such as the reticular thalamus, which receives a main cortical projection, and hypothalamic regions implicated in sleep regulation, such as the ventrolateral preoptic area and dorsal median preoptic nucleus. Fos activation was not observed in many other brain regions. In the reticular thalamus and somatosensory cortex, the number of IL1β-immunoreactive glial cells increased. Further, the number of NGF-immunoreactive cells in the primary somatosensory cortex and magnocellular preoptic nucleus increased on the IL1β-injected side. These results are consistent with the hypothesis that sleep is initiated within the cortex after the local activation of specific cytokines and that whole organism sleep is coordinated via cortical connections with the subcortical sites. © 2006 Elsevier B.V. All rights reserved.