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A temporal shift in the circuits mediating retrieval of fear memory

Nature volume 519, pages 460463 (26 March 2015) | Download Citation


Fear memories allow animals to avoid danger, thereby increasing their chances of survival. Fear memories can be retrieved long after learning1,2, but little is known about how retrieval circuits change with time3,4. Here we show that the dorsal midline thalamus of rats is required for the retrieval of auditory conditioned fear at late (24 hours, 7 days, 28 days), but not early (0.5 hours, 6 hours) time points after learning. Consistent with this, the paraventricular nucleus of the thalamus (PVT), a subregion of the dorsal midline thalamus, showed increased c-Fos expression only at late time points, indicating that the PVT is gradually recruited for fear retrieval. Accordingly, the conditioned tone responses of PVT neurons increased with time after training. The prelimbic (PL) prefrontal cortex, which is necessary for fear retrieval5,6,7, sends dense projections to the PVT8. Retrieval at late time points activated PL neurons projecting to the PVT, and optogenetic silencing of these projections impaired retrieval at late, but not early, time points. In contrast, silencing of PL inputs to the basolateral amygdala impaired retrieval at early, but not late, time points, indicating a time-dependent shift in retrieval circuits. Retrieval at late time points also activated PVT neurons projecting to the central nucleus of the amygdala, and silencing these projections at late, but not early, time points induced a persistent attenuation of fear. Thus, the PVT may act as a crucial thalamic node recruited into cortico-amygdalar networks for retrieval and maintenance of long-term fear memories.

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We thank G. Manzano-Nieves for help with the optogenetic experiments, A. C. Felix-Ortiz for technical advice, and K. M. Tye for comments on the manuscript. We thank K. Deisseroth for viral constructs and the UNC Vector Core Facility for viral packaging. This study was supported by the NIH grants R01-MH058883, and P50-MH086400, and a grant from the University of Puerto Rico President’s Office to G.J.Q.; the MBRS-RISE Program (R25-GM061838) to K.Q.L.; and NSF grant DBI-0115825 and RCMI grant 8G12-MD007600 for the Confocal Microscope Facility.

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  1. Department of Psychiatry, University of Puerto Rico School of Medicine, PO Box 365067, San Juan 00936, Puerto Rico

    • Fabricio H. Do-Monte
    • , Kelvin Quiñones-Laracuente
    •  & Gregory J. Quirk
  2. Department of Anatomy & Neurobiology, University of Puerto Rico School of Medicine, P.O. Box 365067, San Juan 00936, Puerto Rico

    • Fabricio H. Do-Monte
    • , Kelvin Quiñones-Laracuente
    •  & Gregory J. Quirk


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F.H.D.-M. performed behavioural, immunocytochemical and optogenetic experiments. F.H.D.-M. and K.Q.-L. performed single-unit recording in anaesthetized rats. K.Q.-L. performed single-unit recording experiments in behaving rats. F.H.D.-M., K.Q.-L. and G.J.Q. designed the study, interpreted results, and wrote the paper.

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The authors declare no competing financial interests.

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Correspondence to Fabricio H. Do-Monte.

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