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We previously showed that variation in the expression of the neurotrophin tyrosine kinase receptor type 3 (<jats:italic>NTRK3<\/jats:italic>) in both PAND patients and a transgenic mouse model (Tg<jats:italic>NTRK3<\/jats:italic>) may have a role in PAND pathophysiology.<\/jats:p><jats:p>Our study examines hippocampal function and activation of the brain fear network in Tg<jats:italic>NTRK3<\/jats:italic>mice. Tg<jats:italic>NTRK3<\/jats:italic>mice showed increased fear memories accompanied by impaired extinction, congruent with an altered activation pattern of the amygdala\u2014hippocampus\u2014medial prefrontal cortex fear circuit. Moreover, Tg<jats:italic>NTRK3<\/jats:italic>mice also showed an unbalanced excitation-to-inhibition ratio in the hippocampal cornu ammonis 3 (CA3)\u2013CA1 subcircuit toward hyperexcitability. The resulting hippocampal hyperexcitability underlies the enhanced fear memories, as supported by the efficacy of tiagabine, a GABA reuptake inhibitor, to rescue fear response.<\/jats:p><jats:p>The fearful phenotype appears to be the result of hippocampal hyperexcitability and aberrant fear circuit activation. We conclude that<jats:italic>NTRK3<\/jats:italic>plays a role in PAND by regulating hippocampus-dependent fear memories.<\/jats:p>","DOI":"10.1523\/jneurosci.2161-13.2013","type":"journal-article","created":{"date-parts":[[2013,9,18]],"date-time":"2013-09-18T17:27:41Z","timestamp":1379525261000},"page":"15259-15271","source":"Crossref","is-referenced-by-count":40,"title":["Hippocampal Hyperexcitability Underlies Enhanced Fear Memories in Tg<i>NTRK3<\/i>, a Panic Disorder Mouse 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