Lateralized role of prefrontal cortex in guiding orienting behavior

Orienting movements are essential to sensory-guided reward-seeking behaviors. Prefrontal cortex (PFC) is believed to exert top-down control over a range of goal-directed behaviors and is hypothesized to bias sensory-guided movements. However, the nature of PFC involvement in controlling sensory-guided orienting behaviors has remained largely unknown. Here, we trained rats on a delayed two-alternative forced-choice task requiring them to hold an orienting decision in working memory before execution is cued. Medial PFC (mPFC) Inactivation using either Muscimol or optogenetics impaired choice behavior. However, optogenetic impairment depended on the specific trial epoch during which inactivation took place. In particular, we found a lateralized role for mPFC during the presentation of instruction cues but this role became bilateral when inactivation occurred later in the delay period. Electrophysiological recording of multiple single-unit activity further provided evidence that this lateralized selectivity is cell-type specific. Our results suggest a previously unknown role of mPFC in mediating sensory-guided representation of orienting behavior and a potentially distinct cell-type specific role in shaping such representation across time.