Roles of prefrontal cortex and mediodorsal thalamus in task engagement and behavioral flexibility.

Roles of prefrontal cortex and mediodorsal thalamus in task engagement and behavioral flexibility.

J Neurosci. 2018 Feb 07;:

Authors: Marton T, Seifikar H, Luongo FJ, Lee AT, Sohal VS

Abstract
Behavioral tasks involving auditory cues activate inhibitory neurons within auditory cortex, leading to a reduction in the amplitude of auditory evoked response potentials (ERPs). One hypothesis is that this process -- termed 'task engagement'- may enable context-dependent behaviors. Here we set out to determine 1) whether the medial prefrontal cortex (mPFC) plays a role in task engagement, and 2) how task engagement relates to the context-dependent processing of auditory cues in male and female mice performing a decision making task that can be guided by either auditory or visual cues. We found that, in addition to auditory ERP suppression, task-engagement is associated with increased mPFC activity and an increase in theta band (4-7 Hz) synchronization between the mPFC and auditory cortex. Optogenetically inhibiting the mPFC eliminates the task engagement-induced auditory ERP suppression, while also preventing mice from switching between auditory and visual cue-based rules. However, mPFC inhibition, which eliminates task engagement-induced auditory ERP suppression, did not prevent mice from making decisions based on auditory cues. Furthermore, a more specific manipulation - selective disruption of mPFC outputs to the mediodorsal (MD) thalamus - is sufficient to prevent switching between auditory and visual rules, but does not affect auditory ERPs. Based on these findings we conclude that: (1) the mPFC contributes to both task engagement and behavioral flexibility; (2) mPFC-MD projections are important for behavioral flexibility but not task engagement; (3) task engagement, evidenced by the suppression of cortical responses to sensory input, is not required for sensory-cue guided decision making.SIGNIFICANCE STATEMENTWhen rodents perform choice-selection tasks based on sensory cues, neural responses to these cues are modulated as compared to task-free conditions. Here we demonstrate that this phenomenon depends on the prefrontal cortex, and thus represents a form of "top-down" regulation. However, we also show that this phenomenon is not critical for task performance, as rodents can make decisions based on specific sensory cues even when the task-dependent modulation of responses to those cues is abolished. Furthermore, disrupting one specific set of prefrontal outputs impairs rule switching but not the task-dependent modulation of sensory responses. These results show that the prefrontal cortex comprises multiple circuits that mediate dissociable functions related to behavioral flexibility and sensory processing.

PMID: 29437889 [PubMed - as supplied by publisher]

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