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BTBD3 is a putative transcription factor implicated in dendritic pruning in developing primary sensory cortices. We assessed whether BTBD3 also regulates neural circuit formation within limbic cortico-striato-thalamo-cortical circuits and behaviors related to OCD in mice. Behavioral phenotypes associated with OCD that are measurable in animals include compulsive-like behaviors and reduced exploration. We tested <jats:italic>Btbd3<\/jats:italic> wild-type, heterozygous, and knockout mice for compulsive-like behaviors including cage-mate barbering, excessive wheel-running, repetitive locomotor patterns, and reduced goal-directed behavior in the probabilistic learning task (PLT), and for exploratory behavior in the open field, digging, and marble-burying tests. <jats:italic>Btbd3<\/jats:italic> heterozygous and knockout mice showed excessive barbering, wheel-running, impaired goal-directed behavior in the PLT, and reduced exploration. Further, chronic treatment with fluoxetine, but not desipramine, reduced barbering in <jats:italic>Btbd3<\/jats:italic> wild-type and heterozygous, but not knockout mice. In contrast, <jats:italic>Btbd3<\/jats:italic> expression did not alter anxiety-like, depression-like, or sensorimotor behaviors. We also quantified dendritic morphology within anterior cingulate cortex, mediodorsal thalamus, and hippocampus, regions of high <jats:italic>Btbd3<\/jats:italic> expression. Surprisingly, <jats:italic>Btbd3<\/jats:italic> knockout mice only showed modest increases in spine density in the anterior cingulate, while dendritic morphology was unaltered elsewhere. Finally, we virally knocked down <jats:italic>Btbd3<\/jats:italic> expression in whole, or just dorsal, hippocampus during neonatal development and assessed behavior during adulthood. Whole, but not dorsal, hippocampal <jats:italic>Btbd3<\/jats:italic> knockdown recapitulated <jats:italic>Btbd3<\/jats:italic> knockout phenotypes. Our findings reveal that hippocampal <jats:italic>Btbd3<\/jats:italic> expression selectively modulates compulsive-like and exploratory behavior.<\/jats:p>","DOI":"10.1038\/s41398-019-0558-7","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T15:03:09Z","timestamp":1568041389000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Btbd3 expression regulates compulsive-like and exploratory behaviors in mice"],"prefix":"10.1038","volume":"9","author":[{"given":"Summer L.","family":"Thompson","sequence":"first","affiliation":[]},{"given":"Amanda C.","family":"Welch","sequence":"additional","affiliation":[]},{"given":"Emily V.","family":"Ho","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o M.","family":"Bessa","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Portugal-Nunes","sequence":"additional","affiliation":[]},{"given":"M\u00f3nica","family":"Morais","sequence":"additional","affiliation":[]},{"given":"Jared W.","family":"Young","sequence":"additional","affiliation":[]},{"given":"James A.","family":"Knowles","sequence":"additional","affiliation":[]},{"given":"Stephanie C.","family":"Dulawa","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"558_CR1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. 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