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Pharmacoresistance and comorbidities pose significant challenges to its treatment necessitating the development of non\u2010pharmacological approaches. In an earlier study, exposure to enriched environment (EE) reduced seizure frequency and duration and ameliorated chronic epilepsy\u2010induced depression in rats. However, the cellular basis of beneficial effects of EE remains unknown. Accordingly, in the current study, we evaluated the effects of EE in chronic epilepsy\u2010induced changes in behavioral hyperexcitability, synaptic transmission, synaptophysin (SYN), and calbindin (CB) expression, hippocampal subfield volumes and cell density in male Wistar rats. Epilepsy was induced by lithium\u2013pilocarpine\u2010induced status epilepticus. Chronic epilepsy resulted in behavioral hyperexcitability, decreased basal synaptic transmission, increased paired\u2010pulse facilitation ratio, decreased hippocampal subfields volumes. Moreover, epileptic rats showed decreased synaptophysin and CB expression in the hippocampus. Six weeks post\u2010SE, epileptic rats were exposed to EE for 2\u00a0weeks, 6\u00a0hr\/day. EE significantly reduced the behavioral hyperexcitability and restored basal synaptic transmission correlating with increased expression of SYN and CB. Our results reaffirm the beneficial effects of EE on behavior in chronic epilepsy and establishes some of the putative cellular mechanisms. Since drug resistance and comorbidities are a major concern in TLE, we propose EE as a potent non\u2010pharmacological treatment modality to mitigate these changes in chronic epilepsy.<\/jats:p>","DOI":"10.1002\/jnr.24823","type":"journal-article","created":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T12:44:09Z","timestamp":1615639449000},"page":"1646-1665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Enriched environment ameliorates chronic temporal lobe epilepsy\u2010induced behavioral hyperexcitability and restores synaptic plasticity in CA3\u2013CA1 synapses in male Wistar rats"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-3875","authenticated-orcid":false,"given":"Raghava Jagadeesh","family":"Salaka","sequence":"first","affiliation":[{"name":"Department of Neurophysiology National Institute of Mental Health and Neuro Sciences Bengaluru 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