Biology subjects

Sauvage, M.

Publications and source records attributed to Sauvage, M..

6 recordsLinked to original sources

bioRxiv2026

Circuit-specific reorganization of hippocampal-entorhinal-prefrontal subnetworks supports memory recall across the lifespan

How memories reorganize across brain circuits as they age remains a central question in systems neuroscience. Systems consolidation is thought to progressively shift memory reliance from the hippocampus to distributed cortical networks, yet the contribution of cortical regions beyond the prefrontal cortex and the nature of this shift remains unclear. Here we define the circuit-level organization of remote memory recall across entorhinal, prefrontal, and hippocampal subregions. Using high-resolution activity mapping combined with causal manipulations that leverage natural memory decay, we adapted a murine object-location paradigm to examine memory recall across the lifespan. We find that recall of early remote memories (1 month) selectively depends on a LEC-hippocampal (CA1/CA3) circuit, whereas recall of older memories (6-12 months) recruits a distinct and broader network involving both LEC and MEC together with ACC and CA1. These findings reveal a temporally ordered, circuit-specific reconfiguration of hippocampo-cortical networks and identify the EC as a dynamic hub in remote memory retrieval. Our results refine prevailing systems consolidation theories by showing that memory consolidation is a circuit-specific and temporally ordered process, rather than a passive gradual phenomenon, and position the EC as a central and dynamic component of remote memory retrieval alongside the PFC. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/743925v1_ufig.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@11d2922org.highwire.dtl.DTLVardef@177b02borg.highwire.dtl.DTLVardef@cf0a11org.highwire.dtl.DTLVardef@9e0668_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Single neurons act as a memory buffer for space

Neurons are the fundamental units of cognitive processing. The prevailing view holds that neurons are input-output units that fire action potentials only upon receiving sufficient synaptic input. Here, we demonstrate that this may not be the sole operational mode of neurons in vivo during cognitive tasks, by showing that hippocampal place cells actively maintain firing and preserve spatial information through molecularly defined intrinsic mechanisms. Using in vitro and in vivo recordings coupled with molecular manipulation in mice, we reveal that hippocampal persistent firing during spatial working memory is supported by individual neurons via TRPC4 ion channels. Despite the general belief that persistent activity carries working memory content, we demonstrate that this firing maintains immediate spatial representations and is required for spatial working memory performance. These findings redefine neurons as active contributors to information retention, beyond their traditional role as passive input-output units, potentially reshaping our general understanding of computation in the brain.

neuroscience↗

bioRxiv2022

Inhibitory temporo-parietal effective connectivity is associated with explicit memory performance in older adults

Successful explicit memory encoding is associated with inferior temporal activations and medial parietal deactivations, which are attenuated in aging. Here we used Dynamic Causal Modeling (DCM) of functional magnetic resonance imaging data to elucidate effective connectivity patterns between hippocampus, parahippocampal place area (PPA) and precuneus during encoding of novel visual scenes. In 117 young adults, DCM revealed pronounced activating input from the PPA to the hippocampus and inhibitory connectivity from the PPA to the precuneus during novelty processing, with both being enhanced during successful encoding. This pattern could be replicated in two cohorts (N = 141 and 148) of young and older adults. In both cohorts, older adults selectively exhibited attenuated inhibitory PPA-precuneus connectivity, which correlated negatively with memory performance. Our results provide insight into network dynamics underlying explicit memory encoding and suggest that age-related differences in memory-related network activity are, at least partly, attributable to altered temporo-parietal neocortical connectivity.

neuroscience↗

bioRxiv2021

Functional connectivity and information pathways in the human entorhinal-hippocampal circuitry

AO_SCPLOWBSTRACTC_SCPLOWCortical processing streams for item and contextual information come together in the entorhinal-hippocampal circuitry. Various evidence suggest that information-specific pathways organize the cortical - entorhinal interaction and the circuitrys inner communication along the transversal axis. Here, we leveraged ultra-high field functional imaging and advance Maass, Berron et al. (2015) who report two functional routes segregating the entorhinal cortex (EC) and subiculum. Our data show specific scene processing in the functionally connected posterior-medial EC and distal subiculum. The regions of another route, that connects the anterior-lateral EC and a newly identified retrosplenial-based anterior-medial EC subregion with the CA1/subiculum border, process object and scene information similarly. Our results support topographical information flow in human entorhinal-hippocampal subregions with organized convergence of cortical processing streams and a unique route for contextual information. They characterize the functional organization of the circuitry and underpin its central role in memory function and pathological decline.

neuroscience↗

bioRxiv2021

Remembering the gist of an event over a lifetime depends on the hippocampus

A well-accepted view in memory research is that retrieving the gist of a memory over time depends on the cortex, typically the prefrontal cortex, while retrieving its precision relies on the hippocampus. More recent advances indicate that the hippocampal subfield CA1, as opposed to CA3, remains engaged even for retrieving very remote memories and that this engagement coincides with a maximal recruitment of parahippocampal cortical areas (LEC, MEC, PER and POR)1. Using a time-window comparable to that used in human long-term memory studies, here we show that CA1 is necessary for retrieving the gist of a memory independently of its age while memory precision specifically depends on CA3 in a time-dependent manner. The precision for the memory of a context-footshock association was tested in mice after one day or very remotely (i.e. after 6 months or one year) allowing for the natural fading of the memory trace. Retrieving recent memories engaged both CA1 and CA3 in control mice as revealed by high levels of RNA of the immediate-early gene Arc, strongly tied to synaptic plasticity and memory function. Optogenetic inhibition of CA3 cell firing led to the loss of memory precision, i.e. the retrieval of the gist memory selectively supported by CA1. In contrast, CA1 inhibition abolished memory retrieval and reduced both CA1 and CA3s activity. At very remote tests, controls retrieved only the gist of the event by recruiting CA1 and parahippocampal areas. Retrieving this gist was selectively abrogated upon CA1 optogenetic inactivation that dramatically reduced parahippocampal activity. Our findings indicate that the hippocampus, specifically CA1, is required for gist memory retrieval even for very remote memories that were previously reported to be hippocampal-independent, while CA3 is necessary for recalling precise memories in a time-dependent manner.

neuroscience↗

bioRxiv2019

Mutations in CalDAG-GEFI Lead to Striatal Signaling Deficits and Psychomotor Symptoms in Multiple Species Including Human

Syndromes caused by mutations in Ras-MAP kinase signaling molecules are known as RASopathies and share features such as developmental delay, autistic traits, and cancer. Syndromic features of Rap-MAP kinase signaling defects remain undefined. CalDAG-GEFI is a calcium-responsive Rap-GTPase activator that is enriched in the matrix of the sensorimotor striatum and down-regulated in Huntingtons disease. We show here that CalDAG-GEFI mutations, including striatum-specific deletions and spontaneous mutations in the enzymatic domain, are associated with psychomotor phenotypes in humans, dogs and mice. The identification of these neural mutants was guided by the overt bleeding phenotype in CalDAG-GEFI knockout mice, and then in humans and other species with conserved platelet signaling deficits. Knockout mice exhibit loss of striatal long-term potentiation and deficits in dopamine, acetylcholine and glutamate signaling, along with delayed motor learning and drug-induced perseverative behaviors. Thus, loss of CalDAG-GEFI signaling produces an evolutionarily conserved syndrome characterized by bleeding and psychomotor dysfunction.

neuroscience↗