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

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.journal article2020 Apr2020 03 07importe

Shifting between response and place strategies in maze navigation: effects of training, cue availability and functional inactivation of striatum or hippocampus in rats

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The double-H maze test, a novel, simple, water-escape memory task: Acquisition, recall of recent and remote memory, and effects of systemic muscarinic or NMDA receptor blockade during training

To explore spatial cognition in rodents, research uses maze tasks, which differ in complexity, number of goals and pathways, behavioural flexibility, memory duration, but also in the experimenter's control over the strategy developed to reach a goal (e.g., allocentric vs. egocentric). This study aimed at validating a novel spatial memory test: the double-H maze test. The transparent device made of an alley with two opposite arms at each extremity and two in its centre is flooded. An escape platform is submerged in one arm. For experiments 1-3, rats were released in unpredictable sequences from one of both central arms to favour an allocentric approach of the task. Experiment 1 (3 trials/day over 6 days) demonstrated classical learning curves and evidence for recent and nondegraded remote memory performance. Experiment 2 (2 days, 3 trials/day) showed a dose-dependent alteration of task acquisition/consolidation by muscarinic or NMDA receptor blockade; these drug effects vanished with sustained training (experiment 3; 4 days, 3 trials/day). Experiment 4 oriented rats towards a procedural (egocentric) approach of the task. Memory was tested in a misleading probe trial. Most rats immediately switched from response learning-based to place learning-based behaviour, but only when their initial view on environmental cues markedly differed between training and probe trials. Because this simple task enables the formation of a relatively stable memory trace, it could be particularly adapted to study consolidation processes at a system level or/and the interplay between procedural and declarative-like memory systems

Accelerated epigenetic aging in Huntington's disease involves polycomb repressive complex 1

Loss of epigenetic information during physiological aging compromises cellular identity, leading to de-repression of developmental genes. Here, we assessed the epigenomic landscape of vulnerable neurons in two reference mouse models of Huntington neurodegenerative disease (HD), using cell-type-specific multi-omics, including temporal analysis at three disease stages via FANS-CUT&Tag. We show accelerated de-repression of developmental genes in HD striatal neurons, involving histone re-acetylation and depletion of H2AK119 ubiquitination and H3K27 trimethylation marks, which are catalyzed by polycomb repressive complexes 1 and 2 (PRC1 and PRC2), respectively. We further identify a PRC1-dependent subcluster of bivalent developmental transcription factors that is re-activated in HD striatal neurons. This mechanism likely involves progressive paralog switching between PRC1-CBX genes, which promotes the upregulation of normally low-expressed PRC1-CBX2/4/8 isoforms in striatal neurons, alongside the down-regulation of predominant PRC1-CBX isoforms in these cells (e.g., CBX6/7). Collectively, our data provide evidence for PRC1-dependent accelerated epigenetic aging in HD vulnerable neurons.We thank O. Bildstein, D. Egesi, G. Edomwonyi and A. Isik (LNCA UMR7364) for assistance in animal care. Sequencing was performed by the GenomEast Platform, a member of the ‘France Génomique’ consortium (ANR-10-INSN-0009), nuclei sorting was performed by the Flow Cytometry Platform at IGBMC. This study was supported by the Agence Nationale de la Recherche (ANR-2017-CE12-0027 and ANR-2022-CE12-0033 to K.M), the Fondation de la Recherche Medicale (FRM; Duban price to K.M.), the Centre National de la Recherche Scientifique (CNRS), the University of Strasbourg and the Interdisciplinary Thematic Institute NeuroStra (Strasbourg Uni, to KM and EB, as part of the ITI 2021-2028 program of the University of Strasbourg, CNRS and Inserm, supported by IdEx Unistra (ANR-10-IDEX-0002) and under the framework of the French Program “Investments for the Future”). R.A.V. was supported by post-doctoral fellowship from the IdEx fellowship program (Strasbourg Uni). J.Se. was supported by postdoctoral fellowship from the ANR (ANR-2017-CE12-0027). C.M. was supported by European postdoctoral fellowship (JPND programme, ANR-22-JPWG-0002-01). B.B. and J.Sc were recipients of doctoral fellowship from the French government. B.B. received PhD extension funded by NeuroStra (Strasbourg Uni). N.P. was supported by doctoral fellowship from the ANR (ANR-2022-CE12-0033).Peer reviewe

Spatial memory alterations by activation of septal 5HT1A receptors: no implication of cholinergic septohippocampal neurons

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No facilitation of amphetamine- or cocaine-induced hyperactivity in adult rats after various 192 IgG-saporin lesions in the basal forebrain

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