Reassessing the Role of Histaminergic Tuberomammillary Neurons in Arousal Control
| العنوان: | Reassessing the Role of Histaminergic Tuberomammillary Neurons in Arousal Control |
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| المؤلفون: | Takatoshi Mochizuki, Anne Venner, Elda Arrigoni, Christelle Anaclet, Clifford B. Saper, Thomas E. Scammell, Patrick M. Fuller, Roberto De Luca |
| المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience, vol 39, iss 45 J Neurosci |
| بيانات النشر: | Society for Neuroscience, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Vesicular Inhibitory Amino Acid Transport Proteins, Glutamate decarboxylase, Action Potentials, Inbred C57BL, Medical and Health Sciences, Mice, 0302 clinical medicine, EEG/EMG, Research Articles, gamma-Aminobutyric Acid, Neurons, Glutamate Decarboxylase, wake, General Neuroscience, Chemogenetics, medicine.anatomical_structure, Hypothalamus, GABAergic, Arousal, Sleep Research, Tuberomammillary nucleus, Histamine, Biology, Optogenetics, 03 medical and health sciences, Rare Diseases, Behavioral and Social Science, medicine, Animals, sleep, optogenetics, histidine decarboxylase, Neurology & Neurosurgery, Hypothalamic Area, Psychology and Cognitive Sciences, Neurosciences, Histaminergic, Lateral, Mice, Inbred C57BL, 030104 developmental biology, nervous system, Hypothalamic Area, Lateral, chemogenetics, Sleep, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | The histaminergic neurons of the tuberomammillary nucleus (TMNHDC) of the posterior hypothalamus have long been implicated in promoting arousal. More recently, a role for GABAergic signaling by the TMNHDCneurons in arousal control has been proposed. Here, we investigated the effects of selective chronic disruption of GABA synthesis (via genetic deletion of the GABA synthesis enzyme, glutamic acid decarboxylase 67) or GABAergic transmission (via genetic deletion of the vesicular GABA transporter (VGAT)) in the TMNHDCneurons on sleep–wake in male mice. We also examined the effects of acute chemogenetic activation and optogenetic inhibition of TMNHDCneurons upon arousal in male mice. Unexpectedly, we found that neither disruption of GABA synthesis nor GABAergic transmission altered hourly sleep–wake quantities, perhaps because very few TMNHDCneurons coexpressed VGAT. Acute chemogenetic activation of TMNHDCneurons did not increase arousal levels above baseline but did enhance vigilance when the mice were exposed to a behavioral cage change challenge. Similarly, acute optogenetic inhibition had little effect upon baseline levels of arousal. In conclusion, we could not identify a role for GABA release by TMNHDCneurons in arousal control. Further, if TMNHDCneurons do release GABA, the mechanism by which they do so remains unclear. Our findings support the view that TMNHDCneurons may be important for enhancing arousal under certain conditions, such as exposure to a novel environment, but play only a minor role in behavioral and EEG arousal under baseline conditions.SIGNIFICANCE STATEMENTThe histaminergic neurons of the tuberomammillary nucleus of the hypothalamus (TMNHDC) have long been thought to promote arousal. Additionally, TMNHDCneurons may counter-regulate the wake-promoting effects of histamine through co-release of the inhibitory neurotransmitter, GABA. Here, we show that impairing GABA signaling from TMNHDCneurons does not impact sleep–wake amounts and that few TMNHDCneurons contain the vesicular GABA transporter, which is presumably required to release GABA. We further show that acute activation or inhibition of TMNHDCneurons has limited effects upon baseline arousal levels and that activation enhances vigilance during a behavioral challenge. Counter to general belief, our findings support the view that TMNHDCneurons are neither necessary nor sufficient for the initiation and maintenance of arousal under baseline conditions. |
| وصف الملف: | application/pdf |
| تدمد: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1032-19.2019 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c049ab4c59c1d109fd8349a87b9070e1 https://doi.org/10.1523/jneurosci.1032-19.2019 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c049ab4c59c1d109fd8349a87b9070e1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292401 02706474 |
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| DOI: | 10.1523/jneurosci.1032-19.2019 |