Biology subjects

Herbeaux, K.

Publications and source records attributed to Herbeaux, K..

4 recordsLinked to original sources

bioRxiv2024

40 Hz light stimulation restores early brain dynamics alterations and associative memory in Alzheimer's disease model mice

Visual gamma entrainment using sensory stimuli (vGENUS) is a promising non-invasive therapeutic approach for Alzheimers disease (AD), showing efficacy in improving memory function. However, its mechanisms of action remain poorly understood. Using young AppNL-F/MAPT double knock-in (dKI) mice, a model of early AD, we examined brain dynamics alterations before amyloid plaque onset. High-density EEG recordings and novel metrics from fields outside neuroscience were used to assess brain dynamics fluidity--a measure of the brains ability to transition between activity states. We revealed that dKI mice exhibit early, awake state-specific reductions in brain dynamics fluidity associated with cognitive deficits in complex memory tasks. Daily vGENUS sessions over two weeks restored brain dynamics fluidity and rescued memory deficits in dKI mice. Importantly, these effects built up during the stimulation protocol and persisted after stimulation ended, suggesting long-term modulation of brain function. Based on these results, we propose a "brain dynamics repair" mechanism for vGENUS that goes beyond current amyloid-centric hypotheses. This dual insight - that brain dynamics are both a target for repair and a potential diagnostic tool - provides new perspectives on early Alzheimers disease pathophysiology. Significance StatementGamma ENtrainment Using Sensory stimuli (GENUS), involving 40 Hz rhythmic sensory stimulation, shows promise in improving memory function in Alzheimers disease (AD). We hypothesized that brain dynamics changes could be detected before plaque onset and modulated by vGENUS. Applying techniques from climate science to EEG recordings in young AD model mice, we found reduced brain dynamics fluidity associated with early cognitive deficits. Two weeks of vGENUS restored brain dynamics and improved memory, with effects persisting post-treatment. These findings challenge the amyloid-centric view of AD, introduce a potential early biomarker, and suggest vGENUS acts by "repairing" brain dynamics. Our approach offers new perspectives on early diagnosis and non-invasive interventions for AD and other neurological disorders with disrupted brain dynamics.

neuroscience↗

bioRxiv2024

Coping switches stress evoked network disconnection to a new forebrain network state.

Coping with stress is critical to maintaining mental and physical health. Acute stress is associated with changes in neuronal activity across many brain regions and with the reorganization of cross- region correlations in neurovascular coupling. How neuronal activity itself is coordinated across regions during stress, and how neuronal networks are modified during coping, are unknown. We recorded in rats local field potentials (LFPs) simultaneously from five stress-responsive regions during stress and stress-coping behavior. We characterized network activity by computing cross- region coherence, Granger causality, and phase-amplitude coupling on bipolar derivatives of LFPs in the lateral habenula, basolateral amygdala, dorsal hippocampus, prelimbic cortex, and anterior cingulate cortex. First, we established a stress-coping model in rats. We showed that the behavioral response to acute 10-minute restraint stress returned to baseline after a second restraint 3 hours later. The pre-stress state was characterized by robust global network interactions in the theta (6- 9 Hz) and gamma (45-65 Hz) bands. Stress exposure led to nearly complete loss of connectivity. During coping, the robust connectivity reemerged, but in a new pattern compared to the pre-stress state. Finally, we found that baseline, stressed, and coping states can be predicted with high accuracy (> 90 %) from network activity. Overall, we showed that the acutely stressed brain state was primarily a state of network disconnection, while coping was a new network state rather than a return to baseline.

neuroscience↗

bioRxiv2022

Functional brain-wide network mapping during acute stress exposure in rats: Interaction between the lateral habenula and cortical, amygdalar, hypothalamic and monoaminergic regions.

Upon stress exposure a broad network of structures comes into play in order to provide adequate responses and restore homeostasis. It has been known for decades that the main structures engaged during the stress response are the medial prefrontal cortex, the amygdala, the hippocampus, the hypothalamus, the monoaminergic systems (noradrenaline, dopamine, serotonin), and the periaqueductal gray. The lateral habenula (LHb) is an epithalamic structure directly connected to prefrontal cortical areas and to the amygdala, whereas it functionally interacts with the hippocampus. Also, it is a main modulator of monoaminergic systems. The LHb is activated upon exposure to basically all types of stressors, suggesting it is also involved in the stress response. However, it remains unknown if and how the LHb functionally interacts with the broad stress response network. In the current study we performed in rats a restraint stress procedure followed by immunohistochemical staining of the c-Fos protein throughout the brain. Using Graph Theory-based functional connectivity analyses, we confirm the principal hubs of the stress network (e.g. prefrontal cortex, amygdala, periventricular hypothalamus), and show that the LHb is engaged during stress exposure in close interaction with the medial prefrontal cortex, the lateral septum, and the medial habenula. In addition, we performed DREADD-induced LHb inactivation during the same restraint paradigm in order to explore its consequences on the stress response network. This last experiment gave contrasting results as the DREADD ligand alone, clozapine-N-oxide, was able to modify the network. GRAPHICAL ABSTRACT GRAPHICAL ABSTRACT TEXTIn this study, using immunohistochemical staining of the immediate early gene c-fos and graph theory-based functional correlational analyses, we aimed at unravelling the possible engagement of the lateral habenula (LHb) within the stress response network during acute stress exposure (10-min restraint) in rats. We found that the medial part of the LHb (LHbM) was preferentially engaged, and that this engagement was concomitant to this of structures such as the medial prefrontal cortex (mPFC), the insular cortex (Ins), hypothalamic (PVH) and thalamic (PVT) paraventricular nuclei, the extended amygdala, comprising the Bed nucleus of the stria terminalis (BNST) and the entire amygdala (AMG), as well as the dopaminergic ventral tegmental area (VTA) and the serotonergic dorsal raphe nucleus (RD). This suggests upon stressful situations the LHbM serves as a relay of cortical, thalamic, hypothalamic and temporal information, further transmitted to midbrain monoaminergic systems to probably initiate coping strategies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/491280v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@a423eeorg.highwire.dtl.DTLVardef@32e1aaorg.highwire.dtl.DTLVardef@7d6106org.highwire.dtl.DTLVardef@16cff53_HPS_FORMAT_FIGEXP M_FIG C_FIG

animal behavior and cognition↗

bioRxiv2021

Early memory deficits and extensive brain network disorganization in the AppNL-F/MAPT double knock-in mouse model of familial Alzheimer's disease.

A critical challenge in current research on AD is to clarify the relationship between early neuropathology and network dysfunction associated to the emergence of subtle memory alterations which announce disease onset. In the present work, the new generation AppNL-F/MAPT double knock in (dKI) model was used to evaluate early stages of AD. The initial step of tau pathology was restricted to the perirhinal-entorhinal region, sparing the hippocampus. This discrete neuropathological sign was associated with deficits in the object-place associative memory, one of the earliest recognition memories affected in individuals at risk for developing AD. Analyses of task-dependent c-Fos activation was carried out in 22 brain regions across the medial prefrontal cortex, claustrum, retrosplenial cortex, and medial temporal lobe. Initial hyperactivity was detected in the entorhinal cortex and the claustrum of dKI mice. The retention phase was associated to reduced network efficiency especially across cingulate cortical regions, which may be caused by a disruption of information flow through the retrosplenial cortex. Moreover, the relationship between network global efficiency and memory performance in the WT could predict memory loss in the dKI, further linking reduced network efficiency to memory dysfunction. Our results suggest that early perirhinal-entorhinal pathology is associated with local hyperactivity which spreads towards connected regions such as the claustrum, the medial prefrontal cortex and ultimately the key retrosplenial hub which is needed to relay information flow from frontal to temporal lobes. The similarity between our findings and those reported in the earliest stages of AD suggests that the AppNL-F/MAPT dKI model has a high potential for generating key information on the initial stage of the disease.

neuroscience↗