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The nucleus reuniens (RE) of the ventral midline thalamus is an important anatomical link between the HF and mPFC, and as such is crucially involved in SWM functions that recruit both structures. Little is known, however, regarding the role of RE in other behaviors mediated by this circuit. In the present study, we examined the role of RE in spatial working memory and executive functioning following reversible inactivation of RE with either muscimol or procaine. Rats were implanted with an indwelling cannula targeting RE and trained in a delayed nonmatch to sample spatial alternation T\u2010maze task. For the task, sample and choice runs were separated by moderate or long delays (30, 60, and 120 s). Following asymptotic performance, rats were tested following infusions of drug or vehicle. Muscimol infused into RE impaired SWM at all delays, whereby procaine only impaired performance at the longest delays. Furthermore, RE inactivation with muscimol produced a failure in win\u2010shift strategy as well as severe spatial perseveration, whereby rats persistently made re\u2010entries into incorrect arms during correction trials, despite the absence of reward. This demonstrated marked changes in behavioral flexibility and response strategy. These results strengthen the role of nucleus reuniens as a pivotal link between hippocampus and prefrontal cortex in cognitive and executive functions and suggest that nucleus reuniens may be a potential target in the treatment of CNS disorders such as schizophrenia, attention deficit hyperactivity disorder, addiction, and obsessive\u2010compulsive disorder, whose symptoms are defined by hippocampal\u2010prefrontal dysfunctions.<\/jats:p>","DOI":"10.1002\/hipo.22831","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T14:42:38Z","timestamp":1516632158000},"page":"297-311","source":"Crossref","is-referenced-by-count":94,"title":["Inactivation of nucleus reuniens impairs spatial working memory and behavioral flexibility in the rat"],"prefix":"10.1002","volume":"28","author":[{"given":"Tatiana D.","family":"Viena","sequence":"first","affiliation":[{"name":"Center for Complex Systems and Brain Sciences, Florida Atlantic University Boca Raton Florida 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