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Flexible versus fixed spatial self-ordered response sequencing: Effects of inactivation and neurochemical modulation of ventrolateral prefrontal cortex.

Accepted version
Peer-reviewed

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Authors

Axelsson, Sebastian 
Horiguchi, Naotaka 

Abstract

Previously, studies using human neuroimaging and excitotoxic lesions in non-human primate have demonstrated an important role of ventrolateral prefrontal cortex (vlPFC) in higher order cognitive functions such as cognitive flexibility and the planning of behavioral sequences. In the present experiments, we tested effects on performance of temporary inactivation (using GABA receptor agonists) and dopamine D2 and 5-HT2A receptor blockade of vlPFC via local intracerebral infusions in the marmoset. We trained common marmosets to perform spatial self-ordered sequencing tasks in which one cohort of animals performed 2 and 3 response sequences on a continuously varying spatial array of response options on a touch-sensitive screen. Inactivation of vlPFC produced a marked disruption of accuracy of sequencing which also exhibited significant error perseveration. There were somewhat contrasting effects of D2 and 5HT2A receptor blockade, with the former producing error perseveration on incorrect trials, though not significantly impairing accuracy overall, and the latter significantly impairing accuracy but not error perseveration. A second cohort of marmosets were directly compared on performance of fixed versus variable spatial arrays. 3 Inactivation of vlPFC again impaired self-ordered sequencing, but only with varying, and not fixed spatial arrays, the latter leading to the consistent use of fewer, preferred sequences. These findings add to evidence that vlPFC is implicated in goal-directed behavior that requires higher-order response heuristics that can be applied flexibly over different (variable), as compared to fixed stimulus exemplars. They also show that dopaminergic and serotonergic chemomodulation has distinctive effects on such performance.

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Journal Title

The Journal of Neuroscience

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Journal ISSN

0270-6474

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Publisher

Society for Neuroscience

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All rights reserved
Sponsorship
Wellcome Trust (104631/Z/14/Z)
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