Biology subjects

Goutagny, R.

Publications and source records attributed to Goutagny, R..

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↗

bioRxiv2023

State dependent constraints on claustrocortical communication and function

Neural activity in the claustrum has been associated with a range of vigilance states, yet the activity patterns and efficacy of synaptic communication of identified claustrum neurons have not been thoroughly determined. Here we show that claustrum neurons projecting to the retrosplenial cortex were most active during synchronized cortical states such as non-rapid-eye-movement (NREM) sleep and were suppressed during increased cortical desynchronization in arousal, movement, and REM sleep. The efficacy of claustrocortical signaling was also increased during NREM and diminished during movement due in part to increased cholinergic tone. Finally, claustrum activation during NREM sleep enhanced memory consolidation through the phase-resetting of cortical delta waves. Therefore, claustrocortical communication is constrained to function most effectively during cognitive processes associated with synchronized cortical states, such as memory consolidation. Key PointsO_LIClaustrum neurons are suppressed/activated during desynchronized/synchronized cortical states C_LIO_LIClaustrocortical connectivity is increased in non-REM and suppressed during movement C_LIO_LIClaustrocortical communication is heightened during low cholinergic tone C_LIO_LIClaustrum - modulated cortical delta waves enhance the consolidation of a labile memory C_LI

neuroscience↗

bioRxiv2022

Hippocampal gamma oscillations form complex ensembles modulated by behavior and learning

The hippocampus and the entorhinal cortex display a rich oscillatory activity, believed to support neural information processing in key cognitive functions1. In the hippocampal region CA1, a "slow gamma" rhythm (30-80 Hz) generated in CA3 would support memory retrieval whereas a "medium gamma" rhythm (60-120 Hz) generated in the entorhinal cortex would support memory encoding2,3. However, descriptions involving discrete gamma sub-bands can only partially account for the haphazard diversity of oscillatory behaviors observed in individual recordings during spatial navigation behavior. Here, we stress that transient gamma oscillatory episodes at any frequency or phase relative to the ongoing theta (4-12 Hz) rhythm can be recorded at any layer within CA1. Eventually, the commonly reported averages are dominated by a minority of very strong power events overshadowing gamma heterogeneity. Nevertheless, we show that such gamma diversity can be naturally explained by a simple mechanistic model, and that behavior-related information (position within a maze) can be decoded from most individual gamma events, despite their low power and erratic-like nature. Our results indicate that behavior specifically shapes ensembles of irregular hippocampal gamma oscillations, in a way which evolves with learning, depends on the hippocampal layer and is hard to reconcile with the hypothesis of rigid, narrowly tuned gamma sub-bands. Beyond randomness, the pervasive gamma diversity may thus reflect complexity at the "fringe-of-synchrony"4 likely functional but invisible to classic average-based analyses.

neuroscience↗

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↗