4.1 Article

Altered sleep intensity upon DBS to hypothalamic sleep-wake centers in rats

Journal

TRANSLATIONAL NEUROSCIENCE
Volume 12, Issue 1, Pages 611-625

Publisher

DE GRUYTER POLAND SP Z O O
DOI: 10.1515/tnsci-2020-0202

Keywords

deep brain stimulation; sleep; wake behavior; ventrolateral preoptic nucleus; perifornical area of the posterior lateral hypothalamus; slow-wave activity

Categories

Funding

  1. HSM-II program of the Canton of Zurich
  2. Forschungskredit of the University of Zurich
  3. Clinical Research Priority Program Sleep and Health of the University of Zurich

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This study explores the effects of deep brain stimulation on sleep-wake characteristics in rats, finding that high-frequency stimulation of specific hypothalamic regions can modulate the intensity of slow-wave sleep without major impacts on overall sleep-wake architecture.
Deep brain stimulation (DBS) has been scarcely investigated in the field of sleep research. We hypothesize that DBS onto hypothalamic sleep- and wake-promoting centers will produce significant neuromodulatory effects and potentially become a therapeutic strategy for patients suffering severe, drug-refractory sleep-wake disturbances. We aimed to investigate whether continuous electrical high-frequency DBS, such as that often implemented in clinical practice, in the ventrolateral preoptic nucleus (VLPO) or the perifornical area of the posterior lateral hypothalamus (PeFLH), significantly modulates sleep-wake characteristics and behavior. We implanted healthy rats with electroencephalographic/electromyographic electrodes and recorded vigilance states in parallel to bilateral bipolar stimulation of VLPO and PeFLH at 125 Hz and 90 mu A over 24 h to test the modulating effects of DBS on sleep-wake proportions, stability and spectral power in relation to the baseline. We unexpectedly found that VLPO DBS at 125 Hz deepens slow-wave sleep (SWS) as measured by increased delta power, while sleep proportions and fragmentation remain unaffected. Thus, the intensity, but not the amount of sleep or its stability, is modulated. Similarly, the proportion and stability of vigilance states remained altogether unaltered upon PeFLH DBS but, in contrast to VLPO, 125 Hz stimulation unexpectedly weakened SWS, as evidenced by reduced delta power. This study provides novel insights into non-acute functional outputs of major sleep-wake centers in the rat brain in response to electrical high-frequency stimulation, a paradigm frequently used in human DBS. In the conditions assayed, while exerting no major effects on the sleep-wake architecture, hypothalamic high-frequency stimulation arises as a provocative sleep intensity-modulating approach.

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