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The Journal of Neuroscience, July 1, 2001, 21(13):4864-4874

Contrasting Effects of Ibotenate Lesions of the Paraventricular Nucleus and Subparaventricular Zone on Sleep-Wake Cycle and Temperature Regulation

J. Lu¹, Y.-H. Zhang¹, T. C. Chou¹, S. E. Gaus¹, J. K. Elmquist¹, P. Shiromani², and C. B. Saper¹

¹ Department of Neurology and Program in Neuroscience, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, and ² Department of Psychiatry, Brockton Veterans Administration Hospital, Harvard Medical School, Boston, Massachusetts 02115

The suprachiasmatic nucleus (SCN), the circadian pacemaker for the brain, provides a massive projection to the subparaventricular zone (SPZ), but the role of the SPZ in circadian processes has received little attention. We examined the effects on circadian rhythms of sleep, body temperature, and activity in rats of restricted ibotenic acid lesions of the ventral or dorsal SPZ that spared the immediately adjacent paraventricular hypothalamic nucleus (PVH) and the SCN. Ventral SPZ lesions caused profound reduction of measures of circadian index of sleep (by 90%) and locomotor activity (75% reduction) but had less effect on body temperature (50% reduction); dorsal SPZ lesions caused greater reduction of circadian index of body temperature (by 70%) but had less effect on circadian index of locomotor activity (45% reduction) or sleep (<5% reduction). The loss of circadian regulation of body temperature or sleep was replaced by a strong ultradian rhythm (period ~3 hr). Lesions of the PVH, immediately dorsal to the SPZ, had no significant effect on any circadian rhythms that we measured, nor did the lesions affect the baseline body temperature. However, the fever response after intravenous injection of lipopolysaccharide (5 µg/kg) was markedly decreased in the rats with PVH lesions (66.6%) but not dorsal SPZ lesions. These results indicate that circadian rhythms of sleep and body temperatures are regulated by separate neuronal populations in the SPZ, and different aspects of thermoregulation (circadian rhythm and fever response) are controlled by distinct anatomical substrates.

Key words: circadian rhythm; ultradian rhythm; ibotenic acid; suprachiasmatic nucleus; c-Fos; fever

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21134864-11$05.00/0

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