Search

Cognitive flexibility is a hallmark of prefrontal cortical (PFC) function yet little is known about downstream area involvement. The medial dorsal striatum (mDS) receives major projections from the PFC and is uniquely situated to perform the integration of responses with rule information. In this study, we use a novel rule shifting task in rats that mirrors non-human primate and human studies in its temporal precision and counterbalanced responses. We record activity from single neurons in the mDS while rats switch between different rules for reward. Additionally, we pharmacologically inactivate mDS by infusion of a baclofen/muscimol cocktail. Inactivation of mDS impaired the ability to shift to a new rule and increased the number of regressive errors. While recording in mDS, we identified neurons modulated by direction whose activity reflected the conflict between competing rule information. We show that a subset of these neurons was also rule selective, and that the conflict between competing rule cues was resolved as behavioural performance improved. Other neurons were modulated by rule, but not direction. These neurons became selective before behavioural performance accurately reflected the current rule. These data provide an additional locus for investigating the mechanisms underlying behavioural flexibility. Converging lines of evidence from multiple human psychiatric disorders have implicated dorsal striatum as an important and understudied neural substrate of flexible cognition. Our data confirm the importance of mDS, and suggest a mechanism by which mDS mediates abstract cognition functions. [ABSTRACT FROM AUTHOR]

Highlights: [•] Loss of Plaur leads to reduced numbers of medial frontal cortical interneurons. [•] Excess HGF/SF increases hippocampal and medial frontal cortical interneurons. [•] Amygdalar interneurons are not affected by Plaur loss or excess HGF/SF. [•] Fear extinction and attentional set formation are dependent on interneuron number. [ABSTRACT FROM AUTHOR]

Highlights: [•] Thoroughly outline attentional set-shifting tasks across many animal models. [•] Summarize research findings in set-shifting literature. [•] Propose new directions and necessary experiments to fill in important gaps in literature. [ABSTRACT FROM AUTHOR]

Abstract: Schizophrenia is a complex developmental disorder that presents challenges to modern neuroscience in terms of discovering etiology and aiding in effective treatment of afflicted humans. One approach is to divide the constellation of symptoms of human neuropsychiatric disorders into discrete units for study. Multiple animal models are used to study brain ontogeny, response to psychoactive compounds, substrates of defined behaviors. Frontal cortical areas have been found to have abnormal anatomy and neurotransmitter levels in postmortem brains from schizophrenic patients. The mouse model has the advantage of rather straightforward genetic manipulation and offers numerous genetic variations within the same species. However, until recently, the behavioral analyses in the mice lagged behind the primate and rat, especially with respect to testing of frontal cortical regions. Current reports of mouse prefrontal anatomy and function advocate the mouse as a feasible animal model to study prefrontal cortical function. This review highlights the most recent developments from behavioral paradigms for testing orbital and medial prefrontal cortical function in pharmacological and genetic models of human schizophrenia. This article is part of a special issue entitled ‘Schizophrenia’. [Copyright &y& Elsevier]

Many neuropsychiatric diseases are associated with cognitive rigidity linked to prefrontal dysfunction. For example, schizophrenia and Parkinson's disease are associated with performance deficits on the Wisconsin Card Sorting Test, which evaluates attentional set shifting. Although the genetic underpinnings of these disorders can be reproduced in mice, there are few models for testing the functional consequences. Here, we demonstrate that an analog of the Wisconsin Card Sorting Test, developed in marmosets and recently adapted to rats, is a behavioral model of prefrontal function in mice. Systematic analysis demonstrated that formation of the attentional set in mice is dependent on the number of problem sets. We found that mice, like rats and primates, exhibit both affective and attentional sets, and these functions are disrupted by neurotoxic damage to orbitofrontal and medial prefrontal cortical areas, respectively. These data are identical to studies in rats and similar to the deficits reported after prefrontal damage in a comparable task in marmosets. These results provide a behavioral model to assess prefrontal function in mice. [ABSTRACT FROM AUTHOR]