Biology subjects

Remondes, M.

Publications and source records attributed to Remondes, M..

6 recordsLinked to original sources

bioRxiv2025

Chronic Circadian Disturbance Reshapes Hippocampal Connectivity and Cognitive Function

Circadian rhythms regulate a wide range of physiological and cognitive functions, yet the neural mechanisms linking circadian timing to memory remain poorly defined. Here, we identify a direct anatomical projection from the suprachiasmatic nucleus (SCN) to the dorsal hippocampus using complementary viral anterograde, retrograde, and monosynaptic tracing approaches, alongside established indirect pathways via septal and neuromodulatory regions. These findings revise prevailing models that restrict SCN influence on hippocampal function to polysynaptic routes. Functionally, chronic circadian disruption (CCD) induced region-specific metabolic alterations and widespread reorganization of brain-wide functional connectivity (FC). Hypometabolism emerged in the SCN, dentate gyrus, and perirhinal and entorhinal cortices, accompanied by loss of SCN- hippocampal connectivity and compensatory engagement of cortical and subcortical networks. In contrast, the serotonergic dorsal raphe nucleus showed selective hypermetabolism and increased connectivity with the SCN, prefrontal cortex, and hippocampus, suggesting altered neuromodulatory control under circadian misalignment. Behaviorally, CCD produced a selective impairment in object recognition memory, while spatial memory, working memory, cognitive flexibility, and hippocampal synaptic plasticity at the Schaffer collateral-CA1 synapse remained intact. Disrupted functional coupling within perirhinal-entorhinal- hippocampal and prefrontal-hippocampal circuits, together with altered SCN-medial septum- hippocampus connectivity, indicates that cognitive dysfunction arises from desynchronization of distributed brain networks rather than local synaptic failure. Together, these findings provide a new mechanistic framework linking circadian disruption to selective memory impairment and highlight network-level synchrony as a potential target for chronotherapeutic intervention.

neuroscience↗

bioRxiv2025

Auditory Gamma-Frequency Entrainment Abolishes Working Memory Deficits in a Rodent Model of Autism

Individuals on the autism spectrum often exhibit atypical responses to sensory stimuli and difficulties with behavioral regulation, reflecting altered functional patterns in core sensory-motor circuits. While impairments in higher cognitive functions are a hallmark of autism, they remain underexplored in rodent models compared to basic sensory-motor deficits. Furthermore, these sensory processing differences suggest the potential for using patterned auditory stimulation to modulate neural activity and mitigate symptoms. In this study, we investigated higher cognitive function in the valproic acid (VPA) rodent model of autism and evaluated whether auditory entrainment could ameliorate associated impairments. Pregnant dams received an intraperitoneal injection of VPA on embryonic day 12.5 (E12.5), and offspring were subsequently tested on a delayed non-match to place (DNMP) task to assess working memory. VPA-exposed animals showed significantly impaired performance and altered trial-by-trial learning dynamics, indicating deficits in working memory-based decision making. Notably, gamma-frequency auditory stimulation delivered during DNMP sessions led to increased gamma-frequency oscillations, and enhanced power in other bands (theta, beta) across brain regions, as assessed by LFP recordings in freely moving animals. More importantly, such stimulation eliminated the observed working memory impairments, enhancing performance both during and after entrainment. This provides strong evidence for the therapeutic potential of sensory entrainment in reversing autism-related cognitive deficits by modulating dysfunctional neural circuits.

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bioRxiv2024

Optogenetic silencing hippocampal inputs to the retrosplenial cortex causes a prolonged disruption of working memory

Working memory allows us to keep information in memory for the time needed to perform a given task. Such fundamental cognitive ability relies on a neural circuit including the retrosplenial cortex (RSC), connected to several cortical areas, functionally and anatomically, namely primary visual areas, and higher cognitive areas such as the cingulate, midcingulate, and subicular cortices. RSC bears intimate anatomical and functional connections with the hippocampus, and has been implicated in integrating and translating spatial-temporal contextual information between ego- and allocentric reference frames, to compute predictions about goals in goal-directed behaviors. The relative contribution of the hippocampus and retrosplenial cortex in working memory-guided behaviors remains unclear due to the lack of studies reversibly interfering with synapses connecting the two regions during such behaviors. We here used eArch3.0, a hyperpolarizing proton pump, to silence hippocampal axon terminals in RSC while animals perform a standard delayed non-match to place task. We found that such manipulation impairs memory retrieval, significantly decreasing performance and hastening decision-making. Furthermore, we found that such impairment outlasts light-activation of the opsin, its effects being noticed up to 3 subsequent trials.

neuroscience↗

bioRxiv2023

Optogenetic silencing of the Anterior Cingulate Cortex impairs working memory in a delayed non-match to trajectory task

Working memory is a fundamental cognitive ability, allowing us to keep information in memory for the time needed to perform a given task. A complex neural circuit fulfills these functions, among which is the anterior cingulate cortex (CG). Functionally and anatomically connected to the medial prefrontal, retrosplenial, midcingulate and hippocampus, as well as motor cortices, CG has been implicated in retrieving appropriate information when needed to select and control appropriate behavior. The role of cingulate cortex in working memory-guided behaviors remains unclear due to the lack of studies reversibly interfering with its activity during specific epochs of working memory. We used light to activate eNpHR3.0 and thus silence cingulate neurons while animals perform a standard delayed non-match to trajectory task. We found that, while not causing an impairment in eNpHR3.0+ animals when compared to eNpHR3.0-CTRL animals, silencing cingulate neurons during retrieval decreases the mean performance if compared to silencing during encoding. Such retrieval-associated changes are accompanied by longer delays in control animals, consistent with an adaptive recruitment of additional cognitive resources.

neuroscience↗

bioRxiv2023

Mapping functional traces of opioid memories in the rat brain

Addiction to psychoactive substances is a maladaptive learned behavior. Contexts surrounding drug use integrate this aberrant mnemonic process and hold strong relapse triggering ability. Here we asked where context and salience might be concurrently represented in the brain, and found circuitry hubs specific to morphine-related contextual information storage. Starting with a classical rodent morphine-conditioned place preference (CPP) apparatus, we developed a CPP protocol that allows stimuli presentation inside a magnetic resonance imaging scanner, to allow the investigation of whole brain activity during retrieval of drug-context paired associations, as well as resting state functional connectivity under the effect of morphine conditioning. Using fMRI we found context-specific responses to stimulus onset in multiple brain regions, namely limbic, sensory, and striatal. Furthermore, we found increased functional connectivity of lateral septum with regions within and beyond a proposed limbic network, and of the lateral habenula with hippocampal CA1 region, in response to repeated pairings of drug and context. Subsequent exposure to either morphine or saline-conditioned contexts led to significant, context-specific, functional interconnectivity among amygdala, lateral habenula, and lateral septum. Resting-state connectivity of the lateral habenula and amygdala, and that during saline-paired context presentation significantly predicted inter-individual CPP score differences. In sum, our findings show that drug- and saline-paired contexts form distinct memory traces in overlapping functional brain microcircuits, and intrinsic connectivity of habenula, septum, and amygdala likely influences the maladaptive contextual learning in response to opioids. We identify functional mechanisms involved in the acquisition and retrieval of drug-related memories that might be behind the relapse-triggering ability of opioid-associated sensory/contextual cues. Graphical abstractTo investigate the brain-wide regional activity underlying drug addiction Gomes-Ribeiro et al. have developed a rodent morphine-induced CPP (conditioned place preference) protocol whose contextual cues can be consistently presented inside an MRI apparatus. The authors found a common circuitry supporting the neural mechanisms responsible for memorizing an association between distinct contexts, and morphine or the absence thereof, that includes regions involved in affect, reward, contextual perception and memory, with subtle, intriguing, functional specificities ultimately underlying the storage of distinct, individual, CPP memory engrams across the different animals. Animals that are more prone to strong emotional responses (as measured by the baseline resting state amygdala and habenula functional connectivity), exhibit a kind of neural circuit priming effect, and thus develop stronger connectivity patterns in anticipation of stronger morphine addiction behavior. These findings could help to clarify the inter-individual sensitivity to opioids in humans, since despite responding positively to the effects of opioids, many humans do not develop an addiction. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/552221v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1cd4989org.highwire.dtl.DTLVardef@96c76corg.highwire.dtl.DTLVardef@feadd0org.highwire.dtl.DTLVardef@4547b6_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

A Gradient of Hippocampal Inputs to the Medial Mesocortex

Memory-guided decisions depend on complex, finely tuned interactions between hippocampus and medial mesocortical regions anterior cingulate and retrosplenial cortices. The functional circuitry underlying these interactions is unclear. Using viral anatomical tracing, in vitro and in vivo electrophysiology, and optogenetics, we show that such circuitry is characterized by a functional-anatomical gradient. While CG receives excitatory projections from dorsal-intermediate CA1 originated exclusively in stratum pyramidale, retrosplenial cortex also receives inputs originating in stratum radiatum and lacunosum-moleculare, including GAD+ neurons providing long-range GABAergic projections. Such hippocampal projections establish bona fide synapses throughout cortical layers, with retrosplenial cortex densely targeted on its layer 3, around which it receives a combination of inhibitory and excitatory synapses. This gradient is reflected in the pattern of spontaneous oscillatory synchronicity found in the awake-behaving animal, compatible with the known functional similarity of hippocampus with retrosplenial cortex, which contrasts with the encoding of actions and "task-space" by cingulate cortex. HighlightsBoth MMC regions CG and RSC receive monosynaptic connections from the dorsal-intermediate CA1 CG receives layer-sparse excitatory projections exclusively originated from stratum piramidale whereas RSC is targeted densely in superficial layers by a mixed excitatory and inhibitory input originating from all CA1 strata CA1 monosynaptic projections correspond to active synapses onto distinct layers of the two MMC regions Diverse synchrony between MMC and HIPP recorded in vivo is consistent with the rostro-caudal diversity of direct HIPP-MMC connections

neuroscience↗