{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:00:45Z","timestamp":1768510845475,"version":"3.49.0"},"posted":{"date-parts":[[2024,4,8]]},"group-title":"Neuroscience","reference-count":51,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Parvalbumin-positive (PV+) GABAergic interneurons in the dentate gyrus provide powerful perisomatic inhibition of dentate granule cells (DGCs) to prevent overexcitation and maintain the stability of dentate gyrus circuits. Most dentate PV+ interneurons survive status epilepticus, but surviving PV+ interneuron mediated inhibition is compromised in the dentate gyrus shortly after status epilepticus, contributing to epileptogenesis in temporal lobe epilepsy. It is uncertain whether the impaired activity of dentate PV+ interneurons recovers at later times or if it continues for months following status epilepticus. The development of compensatory modifications related to PV+ interneuron circuits in the months following status epilepticus is unknown, although reduced dentate GABAergic inhibition persists long after status epilepticus. We employed PV immunostaining and whole-cell patch-clamp recordings from dentate PV+ interneurons and DGCs in slices from male and female sham controls and intrahippocampal kainate (IHK) treated mice that developed spontaneous seizures months after status epilepticus to study epilepsy-associated changes in dentate PV+ interneuron circuits. We found that the number of dentate PV+ cells was reduced in IHK treated mice. Electrical recordings showed that: 1) Action potential firing rates of dentate PV+ interneurons were reduced in IHK treated mice up to four months after status epilepticus; 2) Spontaneous inhibitory postsynaptic currents (sIPSCs) in DGCs exhibited reduced frequency but increased amplitude in IHK treated mice; and 3) The amplitude of evoked IPSCs in DGCs by optogenetic activation of dentate PV+ cells was upregulated without changes in short-term plasticity. Video-EEG recordings revealed that IHK treated mice showed spontaneous epileptiform activity in the dentate gyrus and that chemogenetic activation of PV+ interneurons abolished the epileptiform activity. Our results suggest not only that the compensatory changes in PV+ interneuron circuits develop after IHK treatment, but also that increased PV+ interneuron mediated inhibition in the dentate gyrus may compensate for cell loss and reduced intrinsic excitability of dentate PV+ interneurons to stop seizures in temporal lobe epilepsy.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Reduced number of dentate PV+ interneurons in TLE mice<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Persistently reduced action potential firing rates of dentate PV+ interneurons in TLE mice<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Enhanced amplitude but decreased frequency of spontaneous IPSCs in the dentate gyrus in TLE mice<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Increased amplitude of evoked IPSCs mediated by dentate PV+ interneurons in TLE mice<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Chemogenetic activation of PV+ interneurons prevents epileptiform activity in TLE mice<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2024.04.05.588316","type":"posted-content","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T05:20:20Z","timestamp":1712553620000},"source":"Crossref","is-referenced-by-count":0,"title":["Activation of hypoactive parvalbumin-positive fast-spiking interneuron restores dentate inhibition to prevent epileptiform activity in the mouse intrahippocampal kainate model of temporal lobe epilepsy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8880-2785","authenticated-orcid":false,"given":"Sang-Hun","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Jin","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4743-1564","authenticated-orcid":false,"given":"Bret N.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024040912251385000_2024.04.05.588316v1.1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00523.2018"},{"key":"2024040912251385000_2024.04.05.588316v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(98)00043-6"},{"key":"2024040912251385000_2024.04.05.588316v1.3","doi-asserted-by":"crossref","first-page":"867323","DOI":"10.3389\/fnsys.2022.867323","article-title":"Zolpidem Profoundly Augments Spared Tonic GABA(A)R Signaling in Dentate Granule Cells Ipsilateral to Controlled Cortical Impact Brain Injury in Mice","volume":"16","year":"2022","journal-title":"Front Syst Neurosci"},{"key":"2024040912251385000_2024.04.05.588316v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19970901)385:3<385::AID-CNE4>3.0.CO;2-#"},{"key":"2024040912251385000_2024.04.05.588316v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24011"},{"key":"2024040912251385000_2024.04.05.588316v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/82900"},{"key":"2024040912251385000_2024.04.05.588316v1.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-02-00506.1996"},{"key":"2024040912251385000_2024.04.05.588316v1.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1747-14.2014"},{"key":"2024040912251385000_2024.04.05.588316v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06899-3"},{"key":"2024040912251385000_2024.04.05.588316v1.10","doi-asserted-by":"crossref","first-page":"101389","DOI":"10.1016\/j.xcrm.2023.101389","article-title":"Targeted therapy improves cellular dysfunction, ataxia, and seizure susceptibility in a model of a progressive myoclonus epilepsy","volume":"5","year":"2024","journal-title":"Cell Rep Med"},{"key":"2024040912251385000_2024.04.05.588316v1.11","doi-asserted-by":"crossref","unstructured":"Folweiler, K. 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