COMPLEMENTARY ROLES OF PRELIMBIC AND INFRALIMBIC CORTEX IN MEDIAL PREFRONTAL CONTROL OF GOAL-DIRECTED BEHAVIOR

The prefrontal cortex is a central brain region crucial for planning, inhibition and flexible control of behavior. In rodents, the medial prefrontal cortex (mPFC) is a heterogeneous structure with multiple, histologically and functionally defined subregions. Multiple lines of evidence, including our previous work, point to opposite roles of prelimbic (PL) and infralimbic (IL) cortices in goal-directed behavior and proactive response inhibition. However, because they are often considered in isolation, the functional relationship between the two subregions is poorly characterized. Here, we performed optogenetic stimulation and electrophysiological recordings in the mPFC of freely moving adult rats performing a simple reaction time task. The animals were trained to press and hold down a lever for a random duration, and release it in response to an auditory signal. We show opposing effects of mPFC inhibition and excitation that vary with mPFC region and task context. Unit activity recorded concurrently in PL and IL indicated antagonistic yet complementary engagement of each subregion across task progression. We propose a reaction-time model of the task and a distinct functional role for PL and IL mapped onto separate model parameters controlling response threshold and temporal expectation. We show that the functional interaction between PL and IL is not fully captured by a purely antagonistic framework, with the areas providing distinct contributions that dynamically evolve with task demands.