Inactivation of nucleus reuniens impairs spatial working memory and behavioral flexibility in the rat.
The hippocampal formation (HF) and medial prefrontal cortex (mPFC) play critical roles in spatial working memory (SWM). 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-maze 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-shift strategy as well as severe spatial perseveration, whereby rats persistently made re-entries 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-compulsive disorder, whose symptoms are defined by hippocampal-prefrontal dysfunctions.
['Viena|Tatiana D|TD|', 'Linley|Stephanie B|SB|', 'Vertes|Robert P|RP|0000-0001-7403-4164']
D000818:Animals D002491:Central Nervous System Agents D056344:Executive Function D008297:Male D018782:Maze Learning D008570:Memory, Short-Term D009118:Muscimol D011343:Procaine D020318:Rats, Long-Evans D065852:Spatial Memory D013997:Time Factors D020651:Ventral Thalamic Nuclei
medial prefrontal cortex hippocampus goal directed behavior orbital cortex perseverative behavior