{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:41:06Z","timestamp":1768509666202,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,7]]},"group-title":"Neuroscience","reference-count":55,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Psychiatric disorders, including anxiety and depression, are highly comorbid in people with epilepsy. However, the mechanisms mediating the shared pathophysiology are currently unknown. There is considerable evidence implicating the basolateral amygdala (BLA) in the network communication of anxiety and fear, a process demonstrated to involve parvalbumin-positive (PV) interneurons. The loss of PV interneurons has been well described in the hippocampus of chronically epileptic mice and in postmortem human tissue of patients with temporal lobe epilepsy (TLE). We hypothesize that a loss of PV interneurons in the BLA may contribute to comorbid mood disorders in epilepsy. To test this hypothesis, we employed a ventral intrahippocampal kainic acid (vIHKA) model of chronic epilepsy in mice, which exhibits profound behavioral deficits associated with chronic epilepsy. We demonstrate a loss of PV interneurons and dysfunction of remaining PV interneurons in the BLA of chronically epileptic mice. Further, we demonstrate altered principal neuron function and impaired coordination of BLA network and behavioral states in chronically epileptic mice. To determine whether these altered network and behavioral states were due to the loss of PV interneurons, we ablated a similar percentage of PV interneurons observed in chronically epileptic mice by stereotaxically injecting AAV-Flex-DTA into the BLA of PV-Cre mice. Loss of PV interneurons in the BLA is sufficient to alter behavioral states, inducing deficits in fear learning and recall of fear memories. These data suggest that compromised inhibition in the BLA in chronically epileptic mice contributes to behavioral deficits, suggesting a novel mechanism contributing to comorbid anxiety and epilepsy.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>Psychiatric illnesses and epilepsy are highly comorbid and negatively impact the quality of life of people with epilepsy. The pathophysiological mechanisms mediating the bidirectional relationship between mood disorders and epilepsy remain unknown and, therefore, treatment options remain inadequate. Here we demonstrate a novel mechanism, involving the loss of PV interneurons in the BLA, leading to a corruption of network and behavioral states in mice. These findings pinpoint a critical node and demonstrate a novel cellular and circuit mechanism involved in the comorbidity of psychiatric illnesses and epilepsy.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.12.05.570112","type":"posted-content","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T20:25:21Z","timestamp":1701980721000},"source":"Crossref","is-referenced-by-count":1,"title":["Loss of PV interneurons in the BLA contributes to altered network and behavioral states in chronically epileptic mice"],"prefix":"10.64898","author":[{"given":"Phillip L.W.","family":"Colmers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pantelis","family":"Antonoudiou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trina","family":"Basu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett","family":"Scapa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Fuller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Maguire","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023121112002169000_2023.12.05.570112v1.1","doi-asserted-by":"crossref","unstructured":"Antonoudiou, Pantelis ., Colmers, Phillip L.W. , Walton, Najah L. , Weiss, Grant L. , Smith, Anne C. , Nguyen, David P. , Lewis, Mike , Quirk, Michael C. , Melon, Laverne C. and Maguire, Jamie L . 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