Reciprocal lateral hypothalamic and raphe GABAergic projections promote wakefulness
| Autor: | Karl Deisseroth, Szabina Furdan, Antoine Roger Adamantidis, Charu Ramakrishnan, Magor L. Lőrincz, Joanna Mattis, Giuseppe Di Giovanni, Mary Gazea, Susan M. Dymecki, Lief E. Fenno, Benedek Molnár, Péter Sere, Lukas T Oesch |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Dorsal Raphe Nucleus Male Lateral hypothalamus Biology Optogenetics Arousal 03 medical and health sciences Mice 0302 clinical medicine Dorsal raphe nucleus Neuromodulation Neural Pathways medicine Animals GABAergic Neurons Wakefulness 610 Medicine & health Research Articles Raphe General Neuroscience 030104 developmental biology medicine.anatomical_structure Hypothalamic Area Lateral GABAergic Sleep Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | J Neurosci |
| ISSN: | 0270-6474 |
| Popis: | The lateral hypothalamus (LH), together with multiple neuromodulatory systems of the brain, such as the dorsal raphe nucleus (DR), is implicated in arousal, yet interactions between these systems are just beginning to be explored. Using a combination of viral tracing, circuit mapping, electrophysiological recordings from identified neurons, and combinatorial optogenetics in mice, we show that GABAergic neurons in the LH selectively inhibit GABAergic neurons in the DR, resulting in increased firing of a substantial fraction of its neurons that ultimately promotes arousal. These DRGABAneurons are wake active and project to multiple brain areas involved in the control of arousal, including the LH, where their specific activation potently influences local network activity leading to arousal from sleep. Our results show how mutual inhibitory projections between the LH and the DR promote wakefulness and suggest a complex arousal control by intimate interactions between long-range connections and local circuit dynamics.SIGNIFICANCE STATEMENT:Multiple brain systems including the lateral hypothalamus and raphe serotonergic system are involved in the regulation of the sleep/wake cycle, yet the interaction between these systems have remained elusive. Here we show that mutual disinhibition mediated by long range inhibitory projections between these brain areas can promote wakefulness. The main importance of this work relies in revealing the interaction between a brain area involved in autonomic regulation and another in controlling higher brain functions including reward, patience, mood and sensory coding. |
| Databáze: | OpenAIRE |
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