The dorsal medial habenula minimally impacts circadian regulation of locomotor activity and sleep
| Autor: | Jennifer Gile, Horacio O. de la Iglesia, Jazmine G. Perez, Miriam Ben-Hamo, Eric E. Turner, Glenn Morton, Yun-Wei A. Hsu |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Light Physiology Period (gene) Photoperiod Sleep REM Biology Motor Activity Article 03 medical and health sciences Mice 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Circadian rhythm Sleep Stages Habenula Transcription Factor Brn-3A Suprachiasmatic nucleus Depression Period Circadian Proteins Darkness Circadian Rhythm PER2 CLOCK 030104 developmental biology Endocrinology Suprachiasmatic Nucleus Sleep Neuroscience 030217 neurology & neurosurgery Locomotion PER1 |
| Popis: | In nocturnal rodents, voluntary wheel-running activity (WRA) represents a self-reinforcing behavior. We have previously demonstrated that WRA is markedly reduced in mice with a region-specific deletion of the transcription factor Pou4f1 (Brn3a), which leads to an ablation of the dorsal medial habenula (dMHb). The decrease in WRA in these dMHb-lesioned (dMHbCKO) mice suggests that the dMHb constitutes a critical center for conveying reinforcement by exercise. However, WRA also represents a prominent output of the circadian system, and the possibility remains that the dMHb is a source of input to the master circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. To test this hypothesis, we assessed the integrity of the circadian system in dMHbCKO mice. Here we show that the developmental lesion of the dMHb reduces WRA under both a light-dark cycle and constant darkness, increases the circadian period of WRA, but has no effect on the circadian amplitude or period of home cage activity or the daily amplitude of sleep stages, suggesting that the lengthening of period is a result of the decreased WRA in the mutant mice. Polysomnographic sleep recordings show that dMHbCKO mice have an overall unaltered daily amplitude of sleep stages but have fragmented sleep and an overall increase in total rapid eye movement (REM) sleep. Photoresponsiveness is intact in dMHbCKO mice, but compared with control animals, they reentrain faster to a 6-h abrupt phase delay protocol. Circadian changes in WRA of dMHbCKO mice do not appear to emerge within the central pacemaker, as circadian expression of the clock genes Per1 and Per2 within the SCN is normal. We do find some evidence for fragmented sleep and an overall increase in total REM sleep, supporting a model in which the dMHb is part of the neural circuitry encoding motivation and involved in the manifestation of some of the symptoms of depression. |
| Databáze: | OpenAIRE |
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