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The nucleus reuniens: a key node in the neurocircuitry of stress and depression

Molecular Psychiatry volume 23, pages 579–586 (2018)Cite this article

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Abstract

The hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC–hippocampal pathway, provokes an antidepressant-like behavioral response in the forced swim test and prevents, but does not ameliorate, anhedonia in the chronic mild stress (CMS) model of depression. Additionally, RE lesioning before CMS abrogates the well-known neuromorphological and endocrine correlates of CMS. In summary, this work highlights the importance of the reciprocal connectivity between the hippocampus and PFC in the establishment of stress-induced brain pathology and suggests a role for the RE in promoting resilience to depressive illness.

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Acknowledgements

We thank the excellent technical assistance provided by Mrs D Papassava and Mrs Goreti Pinto. We also thank Dr R Matsas and Dr M Thomaidou (Athens Pasteur Institute), Dr S Pagakis (BRFAA) for providing equipment and Specifar S.A., Greece for providing sertraline. This work was supported by an ‘Education and Lifelong Learning, Supporting Postdoctoral Researchers’, co-financed by the European Social Fund (ESF) and the General Secretariat for Research and Technology, Greece, the Life and Health Sciences Research Institute (ICVS), ON.2—O NOVO NORTE—North Portugal Regional Operational Program 2007/2013 of the National Strategic Reference Framework (NSRF) 2007/2013 through the European Regional Development Fund (ERDF), the Portuguese Foundation for Science and Technology (FCT; grant no. NMC-113934) and an InEurope program funded by International Brain Research Organization. NK was funded for the FST behavioral scoring software by an IKY-Siemens Fellowship of Excellence for Postgraduate Studies. VMS and JFO were funded by FCT and Marie Curie IEF fellowships as well as the Bial Foundation.

Author contributions

VK contributed to the design of the study, performed all experimental procedures, statistical analyses and compiled the first draft. NK contributed to the design of the study, the analysis and interpretation of results and, with AV, participated in some of the experiments; JFO and VMS helped with the electrophysiological analyses. IS and HL-A contributed to the histochemical analyses. IS and OFXA helped with the studies involving stress and data interpretation. ZP-D, KA and NS participated in study design and interpretation of results and provided significant insights. CD supervised and contributed to all parts of this project. All authors contributed to the writing of the manuscript and approved the final manuscript.

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Author notes

  1. Z Papadopoulou-Daifoti: Deceased.

Authors and Affiliations

  1. Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    V Kafetzopoulos, N Kokras, A Vasalou, Z Papadopoulou-Daifoti & C Dalla

  2. First Department of Psychiatry, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece

    N Kokras

  3. Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal

    I Sotiropoulos, J F Oliveira, H Leite-Almeida, V M Sardinha & N Sousa

  4. ICVS/3B’s, PT Government Associate Laboratory, Braga, Portugal

    I Sotiropoulos, J F Oliveira, H Leite-Almeida, V M Sardinha & N Sousa

  5. NeuroAdaptations Group, Max Planck Institute of Psychiatry, Munich, Germany

    O F X Almeida

  6. Department of Pharmacology, University of Ioannina, Ioannina, Greece

    K Antoniou

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Kafetzopoulos, V., Kokras, N., Sotiropoulos, I. et al. The nucleus reuniens: a key node in the neurocircuitry of stress and depression. Mol Psychiatry 23, 579–586 (2018). https://doi.org/10.1038/mp.2017.55

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