Abstract
The ventral midline thalamus contributes to hippocampo-cortical interactions supporting systems-level consolidation of memories. Recent hippocampus-dependent memories rely on hippocampal connectivity remodeling. Remote memories are underpinned by neocortical connectivity remodeling. After a ventral midline thalamus lesion, recent spatial memories are formed normally but do not last. Why these memories do not endure after the lesion is unknown. We hypothesized that a lesion could interfere with hippocampal and/or neocortical connectivity remodeling. To test this hypothesis, in a first experiment male rats were subjected to lesion of the reuniens and rhomboid (ReRh) nuclei, trained in a water maze, and tested in a probe trial 5 or 25 days post-acquisition. Dendritic spines were counted in the dorsal hippocampus and medial prefrontal cortex. Spatial learning resulted in a significant increase of mushroom spines in region CA1. This modification persisted between 5 and 25 days post-acquisition in Sham rats, not in rats with ReRh lesion. Furthermore, 25 days after acquisition, the number of mushroom spines in the anterior cingulate cortex (ACC) had undergone a dramatic increase in Sham rats; ReRh lesion prevented this gain. In a second experiment, the increase of c-Fos expression in CA1 accompanying memory retrieval was not affected by the lesion, be it for recent or remote memory. However, in the ACC, the lesion had reduced the retrieval-triggered c-Fos expression observed 25 days post-acquisition. These observations suggest that a ReRh lesion might disrupt spatial remote memory formation by preventing persistence of early remodeled hippocampal connectivity, and spinogenesis in the ACC.
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Acknowledgements
This work was supported by the Agence Nationale de la Recherche (ANR grant 14-CE13-0029-01), the University of Strasbourg, the CNRS, INSERM, and by the Région Alsace (a territory now belonging to Région Grand Est) which contributed (50%) to the PhD fellowship allocated to M.M.K. (the supplement was provided by the ANR, same grant as above), as well as by the French government which provided a PhD fellowship to T.C. The authors acknowledge Olivier Bildstein, Daniel Egesi and George Edomwony for their precious contribution to animal care, as well as Mathilde Köhler, Manon Gerum, and Martin Deligny for providing appreciable technical help. We also thank Ms Delphine Cochand for her proofreading of the manuscript.
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The authors declare no conflict of interest. The study conformed to the rules of the European Community council directive of 22 September 2010 (2010-63) and of the French Department of Agriculture. All approaches have been validated by a local ethical committee (CREMEAS - authorization n° AL/32/39/02/13). The ANR grant did not depend on any particular clause which might have influenced data collection, analysis, interpretation and reporting.
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Klein, M.M., Cholvin, T., Cosquer, B. et al. Ventral midline thalamus lesion prevents persistence of new (learning-triggered) hippocampal spines, delayed neocortical spinogenesis, and spatial memory durability. Brain Struct Funct 224, 1659–1676 (2019). https://doi.org/10.1007/s00429-019-01865-1
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DOI: https://doi.org/10.1007/s00429-019-01865-1