{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:43:41Z","timestamp":1768873421082,"version":"3.49.0"},"posted":{"date-parts":[[2024,9,14]]},"group-title":"Neuroscience","reference-count":35,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  A previous study discovered a distinct population of GABAergic neurons in the\n                  <jats:underline>ce<\/jats:underline>\n                  ntral\n                  <jats:underline>a<\/jats:underline>\n                  mygdala (CeA) that can be activated by\n                  <jats:underline>g<\/jats:underline>\n                  eneral\n                  <jats:underline>a<\/jats:underline>\n                  nesthesia (CeA\n                  <jats:sub>GA<\/jats:sub>\n                  ) and exert analgesic functions (Hua et al., 2020). To independently reproduce these prior findings and to investigate the electrophysiological properties of CeA\n                  <jats:sub>GA<\/jats:sub>\n                  neurons, we first used 1.2% isoflurane to induce c-Fos activation in the mouse brain and validated the\n                  <jats:italic>Fos<\/jats:italic>\n                  expression by RNAscope\n                  <jats:italic>in situ<\/jats:italic>\n                  hybridization. Indeed, isoflurane induced robust Fos expression in CeA and these Fos\n                  <jats:sup>+<\/jats:sup>\n                  CeA\n                  <jats:sub>GA<\/jats:sub>\n                  neurons are GABAergic neurons (Vgat\n                  <jats:sup>+<\/jats:sup>\n                  ). We next used Fos-TRAP2 method (different from the CANE method used in the prior study) to label CeA\n                  <jats:sub>GA<\/jats:sub>\n                  neurons (tdTomato\n                  <jats:sup>+<\/jats:sup>\n                  ). Our\n                  <jats:italic>ex vivo<\/jats:italic>\n                  electrophysiological recordings in brain slices revealed that compared to Fos-negative CeA neurons, CeA\n                  <jats:sub>GA<\/jats:sub>\n                  neurons had significantly higher excitability and exhibited distinct patterns of action potentials. Chemogenetic activation of Fos-TRAPed CeA\n                  <jats:sub>GA<\/jats:sub>\n                  neurons was effective at increasing pain thresholds in na\u00efve mice and mice with early-phase neuropathic pain 2 weeks after spared nerve injury (SNI). However, the same chemogenetic activation of CeA\n                  <jats:sub>GA<\/jats:sub>\n                  neurons only had modest analgesia in the late phase of SNI at 8 weeks, although it was highly effective in reducing chronic pain-associated anxiety behaviors at this stage. We found that Fos-negative CeA neurons, but not CeA\n                  <jats:sub>GA<\/jats:sub>\n                  neurons, exhibited increased excitability in the late-phase of SNI, suggesting that chronic pain causes a shift in the relative activity of the CeA microcircuit. Interestingly, Fos-negative neurons exhibited much higher expression of K\n                  <jats:sup>+<\/jats:sup>\n                  -Cl\n                  <jats:sup>\u2212<\/jats:sup>\n                  cotransporter-2 (KCC2), and KCC2 expression was downregulated in the CeA in the late-phase of neuropathic pain. These results support the idea that targeting CeA\n                  <jats:sub>GA<\/jats:sub>\n                  neurons may provide therapeutic benefits for pain relief and chronic pain-associated anxiety. Our findings also suggest distinct roles of CeA\n                  <jats:sub>GA<\/jats:sub>\n                  neurons in regulating physiological pain, acute pain, and chronic pain with a possible involvement of KCC2.\n                <\/jats:p>","DOI":"10.1101\/2024.09.11.612553","type":"posted-content","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T01:37:24Z","timestamp":1726450644000},"source":"Crossref","is-referenced-by-count":1,"title":["Distinct roles of general anesthesia activated CeA neurons in acute versus late phase of neuropathic pain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4751-3172","authenticated-orcid":false,"given":"Junli","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1893-4384","authenticated-orcid":false,"given":"Kenta","family":"Furutani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9146-2205","authenticated-orcid":false,"given":"Aidan","family":"McGinnis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3815-4131","authenticated-orcid":false,"given":"Joseph P","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-3688","authenticated-orcid":false,"given":"Ru-Rong","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024091813401110000_2024.09.11.612553v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0632-8"},{"key":"2024091813401110000_2024.09.11.612553v1.2","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.neuron.2016.10.015","article-title":"Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit","volume":"92","year":"2016","journal-title":"Neuron"},{"key":"2024091813401110000_2024.09.11.612553v1.3","doi-asserted-by":"crossref","unstructured":"Adke, A.P. , et al. 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