Differential Effects of Dorsal and Ventral Medial Prefrontal Cortex Inactivation during Natural Reward Seeking, Extinction, and Cue-Induced Reinstatement

Abstract

Rodent dorsal medial prefrontal cortex (mPFC), typically prelimbic cortex, is often described as promoting actions such as reward seeking, whereas ventral mPFC, typically infralimbic cortex, is thought to promote response inhibition. However, both dorsal and ventral mPFC are necessary for both expression and suppression of different behaviors, and each region may contribute to different functions depending on the specifics of the behavior tested. To better understand the roles of dorsal and ventral mPFC in motivated behavior we pharmacologically inactivated each area during operant fixed ratio 1 (FR1) seeking for a natural reward (sucrose), extinction, cue-induced reinstatement, and progressive ratio (PR) sucrose seeking in male Long–Evans rats. Bilateral inactivation of dorsal mPFC, but not ventral mPFC increased reward seeking during FR1. Inactivation of both dorsal and ventral mPFC decreased seeking during extinction. Bilateral inactivation of ventral mPFC, but not dorsal mPFC decreased reward seeking during cue-induced reinstatement. No effect of inactivation was found during PR. Our data contrast sharply with observations seen during drug seeking and fear conditioning, indicating that previously established roles of dorsal mPFC = going versus ventral mPFC = stopping are not applicable to all motivated behaviors and/or outcomes. Our results indicate that dichotomous functions of dorsal versus ventral mPFC, if they exist, may align better with other models, or may require the development of a new framework in which these multifaceted brain areas play different roles in action control depending on the behavioral context in which they are engaged.

Chemogenetic Inactivation of Orbitofrontal Cortex Decreases Cue‐induced Reinstatement of Ethanol and Sucrose Seeking in Male and Female Wistar Rats

“…An additional novel element of the current study was afforded by the use of DREADDs in that we were able to make these comparisons of OFC inactivation in homecage, self-administration, and reinstatement tests in the same DREADD-expressing neural ensembles in the same individuals. Performing this many repeated comparisons within subjects is challenging if not impossible using techniques such as local pharmacological manipulation (Arinze and Moorman, 2020;Bianchi et al, 2018) given potential uneven dispersal of pharmacological agents across neuron populations during different infusions as well as the potential cumulative influence of tissue damage on neural signaling in the targeted region (Caballero et al, 2019). Combined with previous studies, our data indicate that OFC plays a limited role in driving reward seeking or consumption when reward is freely available.…”

Sexually divergent cortical control of affective-autonomic integration

“…The rodent homolog of BA25, the infralimbic cortex (IL) (Öngür et al, 2003;Uylings et al, 2003;Vertes, 2004), innervates limbic and stress-regulatory nuclei including the amygdala, thalamus, and hypothalamus (Gabbott et al, 2005;Myers et al, 2016Myers et al, , 2014aWood et al, 2018). Additionally, IL stimulation reduces passive coping and increases pyramidal neuron spine density in male rodents (Caballero et al, 2019;Fuchikami et al, 2015;Selimbeyoglu et al, 2017;van Holstein and Floresco, 2019). Moreover, knockdown of IL glutamatergic output exacerbates chronic stress effects on hypothalamic-pituitary-adrenal (HPA) axis reactivity and vascular function (Myers et al, 2017;Schaeuble et al, 2019).…”

Coordinated prefrontal state transition leads extinction of reward-seeking behaviors

“…Lesion (Fragale et al, 2016), pharmacological inactivation (Caballero et al, 2019;Ramanathan et al, 2018) and optogenetic stimulation (Marek et al, 2018;Sparta et al, 2014) studies provide increasing evidence that PL is a critical locus for extinction of reward-seeking behaviors and conditioned fear. Using an appetitive operant within-session extinction paradigm, we studied the dynamics of PL leading to the extinction of conditioned reward-seeking behavior in rats.…”

“…The rodent prelimbic mPFC (PL), together with the infralimbic mPFC (IL), is implicated in extinguishing reward-seeking behavior (Chen et al, 2013;Jonkman et al, 2009;Moorman and Aston-Jones, 2015;Riaz et al, 2019;Sharpe et al, 2019). Both pharmacological inactivation of PL and optogenetic stimulation of its inhibitory network during the presentation of conditioned stimuli facilitate extinction (Caballero et al, 2019;Sparta et al, 2014). Similarly, optogenetic stimulation of PL projections to the nucleus accumbens reduces reward seeking when reward is associated with risk of aversive reinforcement (Kim et al, 2017).…”