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Hippocampus and Prefrontal Cortex Modulation of Contextual Fear Memory Is Dissociated by Inhibiting De Novo Transcription During Late Consolidation

  • Luciana M. Pereira
  • Caio M. de Castro
  • Lorena T. L. Guerra
  • Thaís M. Queiroz
  • João T. Marques
  • Grace Schenatto Pereira
Article

Abstract

To uncover the factors that dictate the persistence of a memory, it is critical to determine the molecular basis of consolidation. Here, we submitted male adult C57/BL6 mice to contextual fear conditioning using 1US (US: foot-shock, 0.7 mA, 2 s) or 5US, to generate recent (24 to 48 h) and remote (30 days) memories, respectively. To access the functional role of de novo transcription, we injected actinomycin D (ActD: 2.5 ng/side) directly into the dorsal hippocampus (HIP) or dorsomedial prefrontal cortex (dmPFC), 0 (early consolidation) or 12 h (late consolidation) after training. Our results showed that de novo transcription at 0 h was required for recent and remote memories. However, 12 h was a critical time point to memory persistence. In the dHIP, de novo transcription at 12 h post-training differentiated the recent memory from the remote. In the dmPFC, ActD affected memory formation depending on the training intensity (1 or 5US). Specifically, freezing was amplified after 5US conditioning. Furthermore, inhibiting de novo transcription at 12 h post-training in the dmPFC rapidly increased c-Fos expression in the amygdala. Altogether, our results indicate that contextual fear memory duration is particularly sensitive to de novo transcription in the dHIP and dmPFC, at a specific time point of late consolidation.

Keywords

Contextual fear memory Late consolidation Dorsal hippocampus Dorsomedial prefrontal cortex De novo transcription 

Notes

Acknowledgments

We thank the members of the Núcleo de Neurociências for helpful discussion on conceiving this work. We also thank Prof. Kasia Radwanska and Dr. Abby Basya Finkelstein for helpful comments and correction of English on this manuscript.

Funding Information

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (PVE 401273/2014), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Procad 88881.068460/2014-01), and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (APQ01396-15).

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Authors and Affiliations

  1. 1.Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  2. 2.Departamento de Bioquímica e Imunologia, Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil

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