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Prefrontal circuits signaling active avoidance retrieval and extinction

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Abstract

Objective

Neurons in PL and IL project densely to two areas implicated in active avoidance: the basolateral amygdala (BLA) and the ventral striatum (VS). We therefore combined c-Fos immunohistochemistry with retrograde tracers to characterize signaling in platform-mediated active avoidance.

Methods

Male rats  were infused with retrograde tracers (CTB, FB) into basolateral amygdala and ventral striatum and conditioned to avoid tone-signaled footshocks by stepping onto a nearby platform. In a subsequent test session, rats received either 2 unreinforced tones (avoidance retrieval) or 15 unreinforced tones (avoidance extinction) followed by analysis of c-Fos combined with fluorescent imaging of retrograde tracers.

Results

Retrieval of avoidance did not activate IL neurons, but did activate PL neurons projecting to BLA, and to a lesser extent VS. Extinction of avoidance activated IL neurons projecting to both BLA and VS, as well as PL neurons projecting to VS.

Conclusions

Our observation that avoidance retrieval is signaled by PL projections to BLA suggests that PL may modulate VS indirectly via BLA, and agrees with other findings implicating BLA in active avoidance. Less expected was the signaling of extinction via PL inputs to VS, which may converge with IL inputs to VS to inhibit expression of avoidance.

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Acknowledgments

Authors thank Marcos J. Sánchez-Navarro, Estefanía M. Medina-Colón, Angelica Minier-Toribio, Ciorana Román-Ortiz, and Kelvin Quiñones-Laracuente for their technical assistant.

Funding

This work was supported by NIH grant R36-MH102968 to CB-R, NIH grants P50-MH086400 and R37-MH058883 to GJQ, and the University of Puerto Rico President’s Office.

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Author notes

  1. Christian Bravo-Rivera

    Present address: Neuroscience Division, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA

Authors and Affiliations

  1. Departments of Psychiatry and Anatomy & Neurobiology, School of Medicine, University of Puerto Rico, P.O. Box 365067, San Juan, 00936-5067, Puerto Rico

    Freddyson J. Martínez-Rivera, Coraly D. Velázquez-Díaz, Marlian Montesinos-Cartagena & Gregory J. Quirk

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  1. Freddyson J. Martínez-Rivera
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Correspondence to Freddyson J. Martínez-Rivera.

Ethics declarations

All procedures were approved by the Institutional Animal Care and Use Committee of the University of Puerto Rico School of Medicine, and the Association for Assessment and Accreditation of Laboratory Animal Care.

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The authors declare that they have no conflict of interest.

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This article belongs to a Special Issue on Psychopharmacology of Extinction.

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Martínez-Rivera, F.J., Bravo-Rivera, C., Velázquez-Díaz, C.D. et al. Prefrontal circuits signaling active avoidance retrieval and extinction. Psychopharmacology 236, 399–406 (2019). https://doi.org/10.1007/s00213-018-5012-7

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