An excitatory lateral hypothalamic circuit orchestrating pain behaviors in mice
| Autor: | Gina M. Leinninger, Yeka Aponte, Miguel A. Arenivar, Justin N. Siemian, Cara B. Borja, Lydia J Erbaugh, Andrew L. Eagle, Alfred J. Robison, Sarah Sarsfield |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Lateral hypothalamus Mouse Animals Genetically Modified 0302 clinical medicine Neural Pathways pain nociception GABAergic Neurons Biology (General) Behavior Animal Morphine General Neuroscience General Medicine Drug Tolerance lateral hypothalamus Analgesics Opioid Neuroanatomical Tract-Tracing Techniques calcium imaging Nociception Parvalbumins Excitatory postsynaptic potential GABAergic Medicine Female Research Article QH301-705.5 Science Glutamic Acid Optogenetics Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Glutamatergic Calcium imaging Noxious stimulus Animals Calcium Signaling optogenetics General Immunology and Microbiology Mice Inbred C57BL Disease Models Animal 030104 developmental biology Microscopy Fluorescence nervous system Hypothalamic Area Lateral chemogenetics Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | eLife, Vol 10 (2021) eLife |
| Popis: | Understanding how neuronal circuits control nociceptive processing will advance the search for novel analgesics. We use functional imaging to demonstrate that lateral hypothalamic parvalbumin-positive (LHPV) glutamatergic neurons respond to acute thermal stimuli and a persistent inflammatory irritant. Moreover, their chemogenetic modulation alters both pain-related behavioral adaptations and the unpleasantness of a noxious stimulus. In two models of persistent pain, optogenetic activation of LHPV neurons or their ventrolateral periaqueductal gray area (vlPAG) axonal projections attenuates nociception, and neuroanatomical tracing reveals that LHPV neurons preferentially target glutamatergic over GABAergic neurons in the vlPAG. By contrast, LHPV projections to the lateral habenula regulate aversion but not nociception. Finally, we find that LHPV activation evokes additive to synergistic antinociceptive interactions with morphine and restores morphine antinociception following the development of morphine tolerance. Our findings identify LHPV neurons as a lateral hypothalamic cell type involved in nociception and demonstrate their potential as a target for analgesia. |
| Databáze: | OpenAIRE |
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