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Going and stopping: dichotomies in behavioral control by the prefrontal cortex

Abstract

The rodent dorsal medial prefrontal cortex (PFC), specifically the prelimbic cortex (PL), regulates the expression of conditioned fear and behaviors interpreted as reward seeking. Meanwhile, the ventral medial PFC, namely the infralimbic cortex (IL), is essential to extinction conditioning in both appetitive and aversive domains. Here we review evidence that supports, or refutes, this “PL-go/IL-stop” dichotomy. We focus on the extinction of conditioned fear and the extinction and reinstatement of cocaine- or heroin-reinforced responding following abstinence. We then synthesize evidence that the PL is essential for developing goal-directed response strategies, while the IL supports habit behavior. Finally, we propose that some functions of the orbital PFC parallel those of the medial PFC in the regulation of response selection. Integration of these discoveries may provide points of intervention for inhibiting untethered drug seeking in drug use disorders, extinction failures in post-traumatic stress disorder, or co-morbidities between the two.

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Figure 1: Subregions of the rodent prefrontal cortex.
Figure 2: Connections and functions of the PL and IL.
Figure 3: Acute cocaine dysregulates PL-dependent action selection.

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Acknowledgements

The authors thank L. Shapiro, A. Allen, L. DePoy, and E. Pitts for valuable feedback and contributions to Figures 1 and 3. This work was supported by PHS DA011717, DA027844 (JRT), MH101477, DA034808 and DA036737 (S.L.G.), and the Connecticut Department of Mental Health and Addiction Services (J.R.T.). The Yerkes National Primate Research Center is supported by the Office of Research Infrastructure Programs/OD P51OD011132.

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S.L.G. and J.R.T. together prepared the manuscript.

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Gourley, S., Taylor, J. Going and stopping: dichotomies in behavioral control by the prefrontal cortex. Nat Neurosci 19, 656–664 (2016). https://doi.org/10.1038/nn.4275

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