A Functional Gradient in the Rodent Prefrontal Cortex Supports Behavioral Inhibition

Abstract

The ability to plan and execute appropriately timed responses to external stimuli is based on a well-orchestrated balance between movement initiation and inhibition. In impulse control disorders involving the prefrontal cortex (PFC) [1], this balance is disturbed, emphasizing the critical role that PFC plays in appropriately timing actions [2-4]. Here, we employed optogenetic and electrophysiological techniques to systematically analyze the functional role of five key subareas of the rat medial PFC (mPFC) and orbitofrontal cortex (OFC) in action control [5-9]. Inactivation of mPFC subareas induced drastic changes in performance, namely an increase (prelimbic cortex, PL) or decrease (infralimbic cortex, IL) of premature responses. Additionally, electrophysiology revealed a significant decrease in neuronal activity of a PL subpopulation prior to premature responses. In contrast, inhibition of OFC subareas (mainly the ventral OFC, i.e., VO) significantly impaired the ability to respond rapidly after external cues. Consistent with these findings, mPFC activity during response preparation predicted trial outcomes and reaction times significantly better than OFC activity. These data support the concept of opposing roles of IL and PL in directing proactive behavior and argue for an involvement of OFC in predominantly reactive movement control. By attributing defined roles to rodent PFC sections, this study contributes to a deeper understanding of the functional heterogeneity of this brain area and thus may guide medically relevant studies of PFC-associated impulse control disorders in this animal model for neural disorders [10-12].

Top‐down and bottom‐up control of stress‐coping

“…However, in general, neural ensembles in the mPFC appear to represent time-sensitive rules and contingencies that confer a bias to guide downstream targets into an appropriate behavioural response. 207,208 Moreover, different prefrontal interneurone types have been shown to shape decision-making in various behavioural assays. Topological distinctions can be made between prelimbic, infralimbic and anterior cingulate cortices, or even more generalised terms such as the ventromedial and dorsomedial prefrontal cortex.…”

“…206 Previous work indicates that both the prelimbic and infralimbic cortex are important for anticipatory behaviour. 207,208 Moreover, different prefrontal interneurone types have been shown to shape decision-making in various behavioural assays. 209,210 Finally, prefrontal projection neurones can have distinct roles based on their target region.…”

Globus pallidus dynamics reveal covert strategies for behavioral inhibition

“…Yet direct support for this hypothesis is sparse (Majid et al 2013). There have been few electrophysiological studies of proactive inhibition at the level of individual neurons (Chen et al 2010;Pouget et al 2011;Hardung et al, 2017;Yoshida et al 2018), and to our knowledge none in GPe. We therefore targeted GPe (often called simply GP in rodents) for investigating neural mechanisms of proactive control.…”

A Toolbox for Optophysiological Experiments in Freely Moving Rats

“…We recorded extracellularly from 18 rats with four different probes during freely moving behavior (Hardung et al, 2017). We implanted 10 rats with fixed arrays (seven rats with optrode MWA, three rats with Microprobes opto-MEA) and eight rats with movable drives (five rats with optetrode, and three rats with VersaDrive-8 Optical).…”