Transient inactivation of the medial prefrontal cortex impairs performance on a working memory-dependent conditional discrimination task.

Abstract

The rodent medial prefrontal cortex (mPFC) has been implicated in working memory function; lesions and inactivation of this region have been shown to result in impairments in spatial working memory (WM) tasks. Our laboratory has developed a tactile-visual conditional discrimination (CD) task, which uses floor insert cues to signal the correct goal-arm choice in a T maze. This task can be manipulated by altering the floor insert cues to be present throughout the trial (CDSTANDARD) or to be present only at the beginning of the trial (CDWM), thus making the task either WM-independent or WM-dependent, respectively. This ability to manipulate the working memory demand of the task while holding all other task features constant allows us to rule out the possibility that confounding performance variables contribute to the observed impairment. A previous study from our lab showed that mPFC inactivation did not impair performance on CDSTANDARD, confirming that mPFC inactivation does not induce sensorimotor or motivational deficits that could impact task performance. To examine whether mPFC inactivation impairs CDWM, the current study transiently inactivated the mPFC with bilateral microinfusions of muscimol immediately prior to testing on the CDWM task. As predicted, CDWM task performance was significantly impaired during the muscimol-infusion session compared with the control saline-infusion sessions. Together with our previous demonstration that the mPFC in not required for CDSTANDARD, these results not only confirm that the mPFC is crucial for working memory, but also set the stage for using the task-comparison approach to investigate corticolimbic interactions during working memory.