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The reuniens and rhomboid nuclei are necessary for contextual fear memory persistence in rats

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Abstract

Memory persistence refers to the process by which a temporary, labile memory is transformed into a stable and long-lasting state. This process involves a reorganization of brain networks at systems level, which requires functional interactions between the hippocampus (HP) and medial prefrontal cortex (mPFC). The reuniens (Re) and rhomboid (Rh) nuclei of the ventral midline thalamus are bidirectionally connected with both regions, and we previously demonstrated their crucial role in spatial memory persistence. We now investigated, in male rats, whether specific manipulations of ReRh activity also affected contextual and cued fear memory persistence. We showed that the permanent ReRh lesion impaired remote, but not recent contextual fear memory. Tone-cued recent and remote fear memory were spared by the lesion. In intact rats, acute chemogenetic ReRh inhibition conducted before recall of either recent or remote contextual fear memories produced no effect, indicating that the ReRh nuclei are not required for retrieval of such memories. This was also suggested by a functional cellular imaging approach, as retrieval did not alter c-fos expression in the ReRh. Collectively, these data are compatible with a role for the ReRh in ‘off-line’ consolidation of a contextual fear memory and support the crucial importance of ventral midline thalamic nuclei in systems consolidation of memories.

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References

  • Bergstrom HC (2016) The neurocircuitry of remote cued fear memory. Neurosci Biobehav Rev 71:409–417

    PubMed  Google Scholar 

  • Born J, Wilhelm I (2012) System consolidation of memory during sleep. Psychol Res 76(2):192–203

    PubMed  Google Scholar 

  • Bousiges O, Neidl R, Majchrzak M, Muller M-A, Barbelivien A, Pereira de Vasconcelos A et al (2013) Detection of histone acetylation levels in the dorsal hippocampus reveals early tagging on specific residues of H2B and H4 histones in response to learning. PLoS ONE 8(3):e57816

    CAS  PubMed  PubMed Central  Google Scholar 

  • Buzsáki G, Wang X-J (2012) Mechanisms of gamma oscillations. Annu Rev Neurosci 35(1):203–225

    PubMed  PubMed Central  Google Scholar 

  • Cassel JC, Cassel JC, Pereira de Vasconcelos A, Loureiro M, Cholvin T, Dalrymple-Alford JC, Vertes RP (2013) The reuniens and rhomboid nuclei: Neuroanatomy, electrophysiological characteristics and behavioral implications. Prog Neurobiol 111:34–52

    PubMed  PubMed Central  Google Scholar 

  • Cholvin T, Loureiro M, Cassel R, Cosquer B, Geiger K, De Sa ND et al (2013) The ventral midline thalamus contributes to strategy shifting in a memory task requiring both prefrontal cortical and hippocampal functions. J Neurosci 33(20):8772–8783

    CAS  PubMed  PubMed Central  Google Scholar 

  • Diekelmann S, Born J (2010) The memory function of sleep. Nat Rev Neurosci 11(2):114–126

    CAS  PubMed  Google Scholar 

  • Dolleman-van-der Weel M, Griffin AL, Ito HT, Shapiro ML, Witter MP, Vertes RP, Allen TA (2019) The nucleus reuniens of the thalamus sits at the nexus of hippocampus and medial prefrontal cortex circuit enabling memory and behavior. Learn Mem 26:191–205

    PubMed  PubMed Central  Google Scholar 

  • Dudai Y, Karni A, Born J (2015) The consolidation and transformation of memory. Neuron 88(1):20–32

    CAS  PubMed  Google Scholar 

  • Ferraris M, Ghestem A, Vicente AF, Nallet-Khosrofian L, Bernard C, Quilichini PP (2018) The nucleus reuniens controls long-range hippocampo-prefrontal gamma synchronization during slow oscillations. J Neurosci 38(12):3026–3038

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frankland PW, Bontempi B (2005) The organization of recent and remote memories. Nat Rev Neurosci 6(2):119–130

    CAS  PubMed  Google Scholar 

  • Gomez JL, Bonaventura J, Lesniak W, Mathews WB, Sysa-Shah P, Rodriguez LA (2017) Chemogenetics revealed: DREADD occupancy and activation via converted clozapine. Science 357(6350):503–507

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hallock HL, Wang A, Griffin AL (2016) Ventral midline thalamus is critical for hippocampal–prefrontal synchrony and spatial working memory. J Neurosci 36(32):8372–8389

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hoover WB, Vertes RP (2007) Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat. Brain Struct Funct 212:149–179

    PubMed  Google Scholar 

  • Hoover WB, Vertes RP (2012) Collateral projections from nucleus reuniens of thalamus to hippocampus and medial prefrontal cortex in the rat: a single and double retrograde fluorescent labeling study. Brain Struct Funct 217(2):191–209

    PubMed  Google Scholar 

  • Jay TM, Witter MP (1991) Distribution of hippocampal CA1 and subicular efferents in the prefrontal cortex of the rat studied by means of anterograde transport of Phaseolus vulgaris-leucoagglutinin. J Comp Neurol 313:574–586

    CAS  PubMed  Google Scholar 

  • Jayachandran M, Linley SB, Schlecht M, MAhler SV, Vertes RP, Allen TA (2019) Prefrontal pathways provide top-down control of memory for sequences of events. Cell Rep 28(3):640–654

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez J, Wolff M, Lecourtier L, Cosquer B, Bontempi B, Dalrymple-Alford J, Cassel JC (2009) The intralaminar thalamic nuclei contribute to remote spatial memory. J Neurosci 29(10):3302–3306

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez J, Herbeaux K, Cosquer B, Engeln M, Muller C, Lazarus C et al (2012) Context-dependent modulation of hippocampal and cortical recruitment during remote spatial memory retrieval. Hippocampus 22(4):827–841

    PubMed  Google Scholar 

  • Loureiro M, Cholvin T, Lopez J, Merienne N, Latreche A, Cosquer B et al (2012) The ventral midline thalamus (reuniens and rhomboid nuclei) contributes to the persistence of spatial memory in rats. J Neurosci 32(29):9947–9959

    CAS  PubMed  PubMed Central  Google Scholar 

  • Majchrzak M, Ferry B, Marchand AR, Herbeaux K, Seillier A, Barbelivien A (2006) Entorhinal cortex lesions disrupt fear conditioning to background context but spare fear conditioning to a tone in the rat. Hippocampus 16(2):114–124

    CAS  PubMed  Google Scholar 

  • Marchand AR, Barbelivien A, Seillier A, Herbeaux K, Sarrieau A, Majchrzak M (2007) Contribution of corticosterone to cued versus contextual fear in rats. Behav Brain Res 183(1):101–110

    CAS  PubMed  Google Scholar 

  • Marchand A, Faugère A, Coutureau E, Wolff M (2014) A role for anterior thalamic nuclei in contextual fear memory. Brain Struct Funct 219(5):1575–1586

    CAS  PubMed  Google Scholar 

  • Marr D (1971) Simple memory: a theory for archicortex. Philos TransR Soc Lond Biol Sci 262:23–81

    CAS  Google Scholar 

  • McAllister DE, McAllister WR (1967) Incubation of fear: an examination of the concept. J Exp Res Personal 2(3):180–190

    Google Scholar 

  • McKenna JT, Vertes RP (2004) Afferent projections to nucleus reuniens of the thalamus. J Comp Neurol 480(2):115–142

    PubMed  Google Scholar 

  • Mei H, Logothetis NK, Eschenko O (2018) The activity of thalamic nucleus reuniens is critical for memory retrieval, but not essential for early phase of "off-line" consolidation. Learn Mem 25:129–137

    CAS  PubMed  PubMed Central  Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Academic Press, London

    Google Scholar 

  • Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106(2):274–285

    CAS  PubMed  Google Scholar 

  • Pickens CL, Golden SA, Adams-Deutsch T, Nair SG, Shaham Y (2009) Long-lasting incubation of conditioned fear in rats. Biol Psychiatry 65:881–886

    PubMed  PubMed Central  Google Scholar 

  • Poulos AM, Mehta N, Lu B, Amir D, Livingston B, Santarelli A et al (2016) Conditioning- and time-dependent increases in context fear and generalization. Learn Mem 23(7):379–385

    PubMed  PubMed Central  Google Scholar 

  • Ramanathan KR, Jin J, Giustino TF, Payne MR, Maren S (2018a) Prefrontal projections to the thalamic nucleus reuniens mediate fear extinction. Nat Commun 9(1):4527

    PubMed  PubMed Central  Google Scholar 

  • Ramanathan KR, Ressler RL, Jin J, Maren S (2018b) Nucleus reuniens is required for encoding and retrieving precise, hippocampal-dependent contextual fear memories in rats. J Neurosci 38(46):9925–9933

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rasch B, Born J (2013) About sleep’s role in memory. Physiol Rev 93(2):681–766

    CAS  PubMed  PubMed Central  Google Scholar 

  • Roy A, Svensson FP, Mazeh A, Kocsis B (2017) Prefrontal-hippocampal coupling by theta rhythm and by 2–5 Hz oscillation in the delta band: the role of the nucleus reuniens of the thalamus. Brain Struct Funct 222(6):2819–2830

    PubMed  PubMed Central  Google Scholar 

  • Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T et al (2012) Fiji—an Open Source platform for biological image analysis. Nat Methods 9(7):676–682

    CAS  PubMed  Google Scholar 

  • Sekeres MJ, Winocur G, Moscovitch M (2018) The hippocampus and related neocortical structures in memory formation. Neuro Lett 680:39–53

    CAS  Google Scholar 

  • Sierra RO, Pedraza LK, Zanona QK, Santana F, Boos FZ, Crestani AP et al (2017) Reconsolidation-induced rescue of a remote fear memory blocked by an early cortical inhibition: involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens. Hippocampus 27(5):596–607

    CAS  PubMed  Google Scholar 

  • Sirota A, Montgomery S, Fujisawa S, Isomura Y, Zugaro M, Buzsáki G (2008) Entrainment of neocortical neurons and gamma oscillations by the hippocampal theta rhythm. Neuron 60(4):683–697

    CAS  PubMed  PubMed Central  Google Scholar 

  • Squire LR, Alvarez P (1995) Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr Opin Neurobiol 5(2):169–177

    CAS  PubMed  Google Scholar 

  • Squire LR, Gennzel L, Wixted JT, Morris RG (2015) Memory consolidation. Cold Spring Harb Perspect Biol 7(8):a021766

    PubMed  PubMed Central  Google Scholar 

  • Troyner F, Bicca MA, Bertoglio LJ (2018) Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long-term maintenance during consolidation. Hippocampus 28(8):602–616

    CAS  PubMed  Google Scholar 

  • Varela C, Kumar S, Yang JY, Wilson M (2014) Anatomical substrates for direct interactions between hippocampus, medial prefrontal cortex, and the thalamic nucleus reuniens. Brain Struct Funct 219(3):911–929

    CAS  PubMed  Google Scholar 

  • Vertes RP, Hoover WB, Do Valle AC, Sherman A, Rodriguez JJ (2006) Efferent projections of reuniens and rhomboid nuclei of the thalamus in the rat. J Comp Neurol 499(5):768–796

    PubMed  Google Scholar 

  • Vetere G, Kenney JW, Tran LM, Xia F, Steadman PE, Parkinson J et al (2017) Chemogenetic interrogation of a brain-wide fear memory network in mice. Neuron 94(2):363–374

    CAS  PubMed  Google Scholar 

  • Wheeler AL, Teixeira CM, Wang AH, Xiong X, Kovacevic N, Lerch JP, McIntosh AR, Parkinson J, Frankland PW (2013) Identification of a functional connectome for long-term fear memory in mice. PLoS Comput Biol 9(1):e1002853

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu W, Südhof TC (2013) A neural circuit for memory specificity and generalization. Science 339(6125):1290–1295

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Agence Nationale de la Recherche (ANR THALAME, Grant 14-CE13-0029-01; coord. J-C.C.), the University of Strasbourg, the CNRS and the INSERM. The French government and the Paul Mandel Fund provided a doctoral fellowship to E.Q. The authors are grateful to O. Bildstein, D. Egesi and G. Edomwony for their excellent assistance in animal care. They also acknowledge L. Lecourtier for his help with the DREADD virus approach, as well as L. Durieux, E. Panzer, T. Delon, S.A. Lazzara, L. Boch and L. Louis-Thayanand for providing appreciable technical help.

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Correspondence to Aline Stéphan.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the European Council Directive (2010/63/EU) and French Agriculture Ministry. All approaches have been validated by the ethical committee of the University of Strasbourg (CREMEAS—authorization #5822-2016062214582106 and #13261-2018012918394046).

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Quet, E., Majchrzak, M., Cosquer, B. et al. The reuniens and rhomboid nuclei are necessary for contextual fear memory persistence in rats. Brain Struct Funct 225, 955–968 (2020). https://doi.org/10.1007/s00429-020-02048-z

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  • DOI: https://doi.org/10.1007/s00429-020-02048-z

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