Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

Abstract

The prefrontal cortex (PFC) guides execution and inhibition of behavior based on contextual demands. In rodents, the dorsal/ prelimbic (PL) medial PFC (mPFC) is frequently considered essential for execution of goal-directed behavior ("go") whereas ventral/ infralimbic (IL) mPFC is thought to control behavioral suppression ("stop"). This dichotomy is commonly seen for fear-related behaviors, and for some behaviors related to cocaine seeking. Overall, however, data for reward-directed behaviors are ambiguous, and few recordings of PL/IL activity have been performed to demonstrate single-neuron correlates. We recorded neuronal activity in PL and IL during discriminative stimulus driven sucrose seeking followed by multiple days of extinction of the reward-predicting stimulus. Contrary to a generalized PL-go/IL-stop hypothesis, we found cue-evoked activity in PL and IL during reward seeking and extinction. Upon analyzing this activity based on resultant behavior (lever press or withhold), we found that neurons in both areas encoded contextually appropriate behavioral initiation (during reward seeking) and withholding (during extinction), where context was dictated by response-outcome contingencies. Our results demonstrate that PL and IL signal contextual information for regulation of behavior, irrespective of whether that involves initiation or suppression of behavioral responses, rather than topographically encoding go vs. stop behaviors. The use of context to optimize behavior likely plays an important role in maximizing utility-promoting exertion of activity when behaviors are rewarded and conservation of energy when not.he prefrontal cortex (PFC) is involved in directing behavior and inhibiting inappropriate responses (1-4). Rodent medial PFC (mPFC) is functionally heterogeneous: prelimbic cortex (PL) is thought to be involved in behavioral execution, and infralimbic cortex (IL) in behavioral suppression, particularly during extinction (4). Fear conditioning studies support this dichotomy. PL stimulation elicits, and inactivation impairs, conditioned fear expression, and PL neurons fire during fear-related cues. Conversely, IL stimulation enhances, and inactivation blocks, extinction of fear conditioning, and IL neurons fire for extinguished cues that previously predicted an aversive stimulus (5, 6).A similar dichotomy is proposed for appetitive behaviors, although support for this is not unequivocal (7). PL inactivation during discriminative stimulus (DS)-driven reward-seeking reduces cue-driven behaviors (8). However, PL inactivation also increases nonspecific (8) and premature lever responding (9, 10), and PL is important in inhibiting responses during a stop-signal reaction time task (11). IL inactivation during DS task performance increases responses generally, including those triggered by a nonrewarded stimulus (NS) (8), increases premature responding on five-choice serial reaction time tasks (12), and increases spontaneous recovery and reinstatement (13). Cocaine seeking is also associated with activation ...

The infralimbic and prelimbic cortices contribute to the inhibitory control of cocaine‐seeking behavior during a discriminative stimulus task in rats

“…In the study by Mihindou and colleagues, PL, but not IL, inactivation disinhibited cocaine-seeking behavior in the presence of the DS−. Of particular interest, in a recent electrophysiology study that used a sucrose-seeking task in a paradigm similar to the present one, IL and PL activity did not show appreciable differences compared to each other during the promotion vs. extinction of the sucrose-seeking behavior (Moorman et al , 2015a). …”

“…Other work using a sucrose-seeking task reports that the IL and PL both encode contextually appropriate behavioral initiation or withholding during a DS task, suggesting a more general role of the IL and PL in encoding information that is used to guide behaviorally appropriate responses (Moorman et al , 2015a). Thus, impaired performance accuracy resulting from IL and PL inactivation in the present task may result from disruption of encoding appropriate external information (e.g., discrete cues).…”

“…Studies using self-administration paradigms indicate that PL and IL activity drive and inhibit, respectively, cocaine seeking during extinction and reinstatement or as part of an incubation of craving test (LaLumiere et al , 2012; Ma et al , 2014; McFarland and Kalivas, 2001). Yet, other work suggests more complicated pictures of the roles of each subregion in promoting or inhibiting motivated behavior (Bossert et al , 2011; Moorman and Aston-Jones, 2015a; Rogers et al , 2008; Van den Oever et al , 2008). …”

Imbalanced Activity in the Orbitofrontal Cortex and Nucleus Accumbens Impairs Behavioral Inhibition

“…Additionally, NAC is involved in the integration of cues processed by frontal lobe regions into reward representations, particularly when the appropriate course of action is uncertain [45]. As a result, negative occasion setting may be impaired because responding appropriately to the target depends on the incorporation of information about the feature, which likely requires communication with frontal lobe regions [46]. Indeed, OFC and NAC may work in concert to encode and represent information about the target, the feature, and the contingency between them, a process that may be impacted during adolescence [9].…”

Ifenprodil attenuates the acquisition and expression of methamphetamine-induced behavioral sensitization and activation of Ras-ERK1/2 cascade in the caudate putamen

“…Given the important function of the PFc and NAc in addiction to psychomotor stimulants (Ferris et al, 2011;Moorman and Aston-Jones, 2015), the protein levels of Ras, pERK1/2/ERK1/2, and DFosB in these regions were also examined. In the PFc, we did not observe any appreciable changes, which is consistent with previous study (Zhao et al, 2014).…”