Dorsal Raphe Serotonin Neurons Mediate CO2-Induced Arousal from Sleep
| Autor: | Benton S. Purnell, Stephanie L. Alberico, Nicole Leibold, Cornelius Gross, Haleigh R. Smith, Callie M. Ginapp, Enrica Audero, Gordon F. Buchanan, Daniel A. Rappoport, Nicole M. Bode, Youngcho Kim |
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| Přispěvatelé: | RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie |
| Rok vydání: | 2018 |
| Předmět: |
Dorsal Raphe Nucleus
Male 0301 basic medicine 5-HT Mice Transgenic Optogenetics SUDDEN UNEXPECTED DEATH BRAIN-STEM Arousal CARBON-DIOXIDE Mice 03 medical and health sciences 0302 clinical medicine Dorsal raphe nucleus Reflex Animals Medicine NUCLEUS IN-VIVO EPILEPSY Research Articles 5-HT receptor RECEPTOR Raphe business.industry General Neuroscience HYPERCAPNIA chemosensation Carbon Dioxide Sudden infant death syndrome serotonin Mice Inbred C57BL 030104 developmental biology CO2 SEIZURES Serotonin Sleep business Neuroscience 030217 neurology & neurosurgery Serotonergic Neurons |
| Zdroj: | Journal of Neuroscience, 38(8), 1915-1925. Society for Neuroscience |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2182-17.2018 |
| Popis: | Arousal from sleep in response to CO2is a critical protective phenomenon. Dysregulation of CO2-induced arousal contributes to morbidity and mortality from prevalent diseases, such as obstructive sleep apnea and sudden infant death syndrome. Despite the critical nature of this protective reflex, the precise mechanism for CO2-induced arousal is unknown. Because CO2is a major regulator of breathing, prevailing theories suggest that activation of respiratory chemo- and mechano-sensors is required for CO2-induced arousal. However, populations of neurons that are not involved in the regulation of breathing are also chemosensitive. Among these are serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) that comprise a component of the ascending arousal system. We hypothesized that direct stimulation of these neurons with CO2could cause arousal from sleep independently of enhancing breathing. Dialysis of CO2-rich acidified solution into DRN, but not medullary raphe responsible for modulating breathing, caused arousal from sleep. Arousal was lost in mice with a genetic absence of 5-HT neurons, and with acute pharmacological or optogenetic inactivation of DRN 5-HT neurons. Here we demonstrate that CO2can cause arousal from sleep directly, without requiring enhancement of breathing, and that chemosensitive 5-HT neurons in the DRN critically mediate this arousal. Better understanding mechanisms underlying this protective reflex may lead to interventions to reduce disease-associated morbidity and mortality.SIGNIFICANCE STATEMENTAlthough CO2-induced arousal is critical to a number of diseases, the specific mechanism is not well understood. We previously demonstrated that serotonin (5-HT) neurons are important for CO2-induced arousal, as mice without 5-HT neurons do not arouse to CO2. Many have interpreted this to mean that medullary 5-HT neurons that regulate breathing are important in this arousal mechanism. Here we found that direct application of CO2-rich aCSF to the dorsal raphe nucleus, but not the medullary raphe, causes arousal from sleep, and that this arousal was lost with genetic ablation or acute inhibition of 5-HT neurons. We propose that 5-HT neurons in the dorsal raphe nucleus can be activated directly by CO2to cause arousal independently of respiratory activation. |
| Databáze: | OpenAIRE |
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