Inactivation of the prelimbic cortex attenuates operant responding in both physical and behavioral contexts

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Abstract

The present experiments aimed to expand our understanding of the role of the prelimbic cortex (PL) in the contextual control of instrumental behavior. Research has previously shown that the PL is involved when the “physical context,” or chamber in which an instrumental behavior is trained, facilitates performance of the instrumental response (Trask, Shipman, Green, & Bouton, 2017). Recently, evidence has suggested that when a sequence of two instrumental behaviors is required to earn a reinforcing outcome, the first response (rather than the physical chamber) can be the “behavioral context” for the second response (Thrailkill, Trott, Zerr, and Bouton, 2016). Could the PL also be involved in this kind of contextual control? Here rats first learned a heterogenous behavior chain in which the first response (i.e., pressing a lever or pulling a chain) was cued by a discriminative stimulus and led to a second stimulus which cued a second response (i.e., pulling a chain or pressing a lever); the second response led to a sucrose reward. When the first and second responses were tested in isolation in the training context, pharmacological inactivation of the PL resulted in a reduction of the first response, but not the second response. When the second response was performed in the “context” of the first response (i.e., as part of the behavior chain) however, PL inactivation reduced the second response. Overall, these results support the idea that the PL is important for mediating the effects of a training context on instrumental responding, whether the context is physical or behavioral.

Introduction

Operant behaviors are weakened when they are tested outside the physical context (e.g., the Skinner box) in which they are learned (e.g., Thrailkill & Bouton, 2015a). The role of context in behavioral control has generally been attributed to the prefrontal cortex (PFC) (Miller & Cohen, 2001). Notably, the prelimbic subregion of the PFC has been identified as being involved in context-appropriate responding in choice paradigms (Haddon and Killcross, 2006, Marquis et al., 2007) and context-based renewal of extinguished operant behaviors (Bossert et al., 2011, Eddy et al., 2016, Fuchs et al., 2007, Fuchs et al., 2005, Palombo et al., 2017, Trask et al., 2017, Willcocks and McNally, 2013). Our work has suggested that rather than having a general role in renewal of extinguished behaviors, the PL selectively promotes the performance of operant behaviors in the context in which they are learned (i.e., acquisition context) (Trask et al., 2017). In that research, we demonstrated that pharmacological inactivation of the PL with baclofen and muscimol (GABA receptor agonists) reduced the response rate of an operant response when it was tested in the context in which it had been trained but not when tested in a non-training context (Trask et al., 2017). Moreover, this inactivation could also block ABA renewal of extinguished behavior (acquisition in context A, extinction in context B, renewal test in context A) but had no effect on ABC renewal (acquisition in context A, extinction in context B, renewal test in context C).

Recent evidence suggests that when two responses must be made in sequence to obtain a reinforcer, only the first response is sensitive to the physical context; the second response is sensitive to the performance of the first response (Thrailkill et al., 2016), what can be termed the “behavioral context”. Briefly, in a heterogenous instrumental chain procedure, a discriminative stimulus (S1) signals the rat to perform the first response (R1), which terminates S1 and intitiates a second stimulus (S2) that signals the rat to perform the second response (R2), which terminates S2 and leads to a food pellet reward (Thrailkill & Bouton, 2015b). Each component of the chain can be tested separately, by presenting S1 or S2 and allowing the opportunity to make either R1 or R2. Using this procedure, we found that while R1 was sensitive to a change in the physical context (i.e., its rate decreased when tested in a non-trained physical context after acquisition), R2 was not (Thrailkill et al., 2016). In fact, R2 appeared to be sensitive to a change in the behavioral context (i.e., the response rate decreased when R2 was tested separately from R1). Further, after extinction of R2, R2 renewed when tested back in the behavioral context in which it had been trained (R1-R2) but not when it was tested in a non-trained behavioral context (R3-R2) (Steinfeld et al., 2019, Thrailkill et al., 2016).

Here, we test the hypothesis that the PL is a key brain structure for the processing of not only physical context but also behavioral context as defined above. To that end, we trained rats to perform a discriminated heterogenous instrumental chain and then tested both R1 and R2 in isolation from each other in the physical acquisition context (Context A), and then the entire chain and R2 in isolation in a non-trained physical context (Context B). In that way, R1 and R2 were tested both within their respective acquisition contexts (Context A for R1; after R1 for R2) and outside their respective acquisition contexts (Context B for R1; in the absence of R1 for R2). We hypothesized that PL inactivation would reduce R2 when tested with R1 (i.e., within its acquisition context) but not when R2 was tested without R1 (i.e., outside of its acquisition context). We also hypothesized that PL inactivation would reduce R1 when tested in context A but not when tested in context B, similar to our previous finding examining a single operant (Trask et al., 2017).

Section snippets

Subjects

The subjects were 32 male Wistar rats purchased from Charles River Laboratories (St. Constance, Quebec, CAN). They were 59–63 days old upon arrival and were individually housed in a room maintained on a 12:12 h light:dark cycle. Experimentation took place during the light period of the cycle. After recovery from the surgical procedures, food restriction was introduced in order to reduce body weights to 90% of baseline. Food restriction was maintained for the duration of the experiment.

Surgery

Once

Results

A total of 12 rats were excluded from data analysis. One rat did not recover from anesthesia. Seven rats were excluded due to misplaced cannulae or excessive cannulae-related tissue damage. Four rats (Rats 7, 8, 25, 31) were excluded from the data set because in at least one test, their proportion baseline score was more than two standard deviations above the mean (z > 2) (Rat 7: Test B.1 z = 3.03, Rat 8: Test A.2 z = 2.97, Test B.1 z = 3.11, Rat 25: Test A.1 z = 2.05, Rat 31: Test A.2

Discussion

Here we investigated the involvement of the PL in behaviors which are dependent on contexts that are either physical or behavioral. The current results indicate that the inactivation of the PL produces the same effect on behaviors which are associated with behavioral contexts as those that are associated with physical contexts. Beyond adding to the list of PL functions, this finding significantly extends our understanding of the role of the PL in contextual processing because it suggests that

Acknowledgements

This research was supported by the University of Vermont Department of Psychological Science and by NIH Grant R01 DA033123 to MEB. EAT was supported by NIH Grant K01 DA044456.

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