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Memory formation orchestrates the wiring of adult-born hippocampal neurons into brain circuits

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Abstract

During memory formation, structural rearrangements of dendritic spines provide a mean to durably modulate synaptic connectivity within neuronal networks. New neurons generated throughout the adult life in the dentate gyrus of the hippocampus contribute to learning and memory. As these neurons become incorporated into the network, they generate huge numbers of new connections that modify hippocampal circuitry and functioning. However, it is yet unclear as to how the dynamic process of memory formation influences their synaptic integration into neuronal circuits. New memories are established according to a multistep process during which new information is first acquired and then consolidated to form a stable memory trace. Upon recall, memory is transiently destabilized and vulnerable to modification. Using contextual fear conditioning, we found that learning was associated with an acceleration of dendritic spines formation of adult-born neurons, and that spine connectivity becomes strengthened after memory consolidation. Moreover, we observed that afferent connectivity onto adult-born neurons is enhanced after memory retrieval, while extinction training induces a change of spine shapes. Together, these findings reveal that the neuronal activity supporting memory processes strongly influences the structural dendritic integration of adult-born neurons into pre-existing neuronal circuits. Such change of afferent connectivity is likely to impact the overall wiring of hippocampal network, and consequently, to regulate hippocampal function.

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Acknowledgements

This work was financially supported by the CNRS, UPS, Agence Nationale de la Recherche (ANR SIMI7 GRAL-12-BS07-0011, ANR-14-CE13-0029-03 ThalaMe). P. P. was supported by a doctoral fellowship from the Région Midi-Pyrénées (#13050241). T. A. was supported by a fellowship from the Ministry of Research, Technology and Higher Education, Republic of Indonesia. We thank Hélène Halley, Stéphane Pech and Brice Ronsin at Toulouse University III for their technical support. We thank Salah El Mestikawy for the gift of VGLUT1 antibody and Marie-Christine Miquel for her help with VGLUT1 immunohistochemistry, Pascal Roullet for advice on behavioral procedures. We also thank the ABC facility from ANEXPLO, Toulouse, for housing mice and Toulouse Réseau Imagerie, FRBT-CBI, for the microscopic platform. Finally, we thank Marie-Christine Miquel, Laure Verret and Lionel Mouledous for helpful comments on the manuscript.

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  1. Research Center on Animal Cognition, Center for Integrative Biology, Université Paul Sabatier, UMR5169 CNRS, 118, route de Narbonne, 31062, Toulouse Cedex 9, France

    Petnoi Petsophonsakul, Kevin Richetin, Trinovita Andraini & Claire Rampon

  2. Department of Physiology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

    Trinovita Andraini

  3. Stem Cell Laboratory for CNS Diseases Modeling, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund Stem Cell Center and MultiPark, Lund University, BMC A10, 221 84, Lund, Sweden

    Laurent Roybon

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  1. Petnoi Petsophonsakul
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Correspondence to Claire Rampon.

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429_2016_1359_MOESM1_ESM.tif

Overview of the experimental groups and paradigms used in this study. Experimental time lines to evaluate the impact of learning (a), consolidation (b), memory retrieval (c, d), novelty (e, f), and extinction (g). (HC: home cage; CE: context exposure; CFC: contextual fear conditioning; A: familiar context A; B: novel context B; EXT: extinction; No-EXT: no extinction, sac: sacrifice) (TIF 22219 KB)

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Petsophonsakul, P., Richetin, K., Andraini, T. et al. Memory formation orchestrates the wiring of adult-born hippocampal neurons into brain circuits. Brain Struct Funct 222, 2585–2601 (2017). https://doi.org/10.1007/s00429-016-1359-x

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