Biology subjects

Rochefort, N. L.

Publications and source records attributed to Rochefort, N. L..

6 recordsLinked to original sources

bioRxiv2026

Neural mechanisms for resilient sensory computation under metabolic stress

Food-restricted mice can solve visual discrimination tasks despite reduced synaptic currents and increased noise resulting from cellular changes in the primary visual cortex. Combining neural recordings and modeling, we study the population structure of the noise and show it is mainly concentrated along task-irrelevant directions in high-dimensional population activity, hence preserving coding on the low-dimensional stimulus manifold. In addition, we predict that food restriction shortens decision times, conserving energy but limiting the evidence accumulation needed for fine discrimination.

neuroscience↗

bioRxiv2025

Movie-trained transformer reveals novel response properties to dynamic stimuli in mouse visual cortex

Understanding how the brain encodes complex, dynamic visual stimuli remains a fundamental challenge in neuroscience. Here, we introduce ViV1T, a transformer-based model trained on natural movies to predict neuronal responses in mouse primary visual cortex (V1). ViV1T outperformed state-of-the-art models in predicting responses to both natural and artificial dynamic stimuli, while requiring fewer parameters and reducing runtime. Despite being trained exclusively on natural movies, ViV1T accurately captured core V1 properties, including orientation and direction selectivity as well as contextual modulation, despite lacking explicit feedback mechanisms. ViV1T also revealed novel functional features. The model predicted a wider range of contextual responses when using natural and model-generated surround stimuli compared to traditional gratings, with novel model-generated dynamic stimuli eliciting maximal V1 responses. ViV1T also predicted that dynamic surrounds elicited stronger contextual modulation than static surrounds. Finally, the model identified a subpopulation of neurons that exhibit contrast-dependent surround modulation, switching their response to surround stimuli from inhibition to excitation when contrast decreases. These predictions were validated through semi-closed-loop in vivo recordings. Overall, ViV1T establishes a powerful, data-driven framework for understanding how brain sensory areas process dynamic visual information across space and time. Code available at github.com/bryanlimy/ViV1T-closed-loop.

neuroscience↗

bioRxiv2025

RatDISCO, a tissue clearing and immunolabelling protocol for large rat brains.

RatDISCO is a simple, cost-effective, and reproducible tissue-clearing protocol optimised for immunolabeling in adult rat brains. It enables robust detection of diverse neuronal subtypes, glial populations, and vasculature, overcoming key limitations in antibody penetration and optical transparency. It is compatible with virally labelled-and transgenic mice, as well as human-derived brain organoids, highlighting its versatility across species and models. Functionally, it enables the detection of activity-dependent markers after behaviour, verified in a rat model of neurodevelopmental disorders, the Fragile X syndrome. These findings highlight RatDISCO as a broadly applicable tool for investigating neuroanatomical and functional alterations in rat models of disorders. HighlightsO_LIOptimised for immunolabeling in adult rat brains C_LIO_LIEnables detection of neurons, glial cells, and vasculature C_LIO_LIAchieves high tissue transparency without requiring specialised equipment. C_LIO_LICompatible with virally labelled mice and human brain organoids C_LIO_LIFacilitates mapping of activity-dependent markers in rat models of neurodevelopmental disorders C_LI

neuroscience↗

bioRxiv2025

Noradrenergic-dependent restoration of visual discrimination in a mouse model of SYNGAP1-related disorder

Atypical sensory processing in neurodevelopmental disorders contributes to cognitive, social, and behavioural disruptions, yet underlying neurophysiological mechanisms remain unclear. Using a mouse model of SYNGAP1 haploinsufficiency (HET), a common monogenic cause of intellectual disability and autism, we investigated visual processing deficits. Syngap HET mice exhibited impaired behavioural visual discriminability, associated with reduced coding precision for visual stimuli in the primary visual cortex (V1). Notably, intrinsic properties of V1 neurons and visual responses under anaesthesia were unaltered, suggesting behavioural state-dependent disruptions in awake Syngap HET mice. Supporting this, both mice and individuals with SYNGAP1 haploinsufficiency exhibited larger pupil size during visual stimulation, implicating neuromodulatory dysfunction. Targeting noradrenergic tone systemically with an 2-adrenergic receptor agonist restored V1 coding precision in Syngap HET mice. Our findings reveal neuromodulatory dysregulation as a novel mechanism underlying sensory disruptions in SYNGAP1-related disorder, highlighting potential therapeutic targets for addressing sensory impairments in neurodevelopmental disorders.

neuroscience↗

bioRxiv2023

Sex-specific resilience of neocortex to food restriction

Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These adaptations are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts to food restriction, and how such adaptations differ across the sexes. Here, we examined how food restriction impacts energy usage and function in the primary visual cortex (V1) of adult male and female mice. Molecular analysis and RNA sequencing in V1 revealed that in males, but not in females, food restriction significantly modulated canonical, energy-regulating pathways, including pathways associated with AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPAR), mammalian target of rapamycin (mTOR), and oxidative phosphorylation. Moreover, we found that in contrast to males, food restriction in females did not significantly affect V1 ATP usage or visual coding precision (assessed by orientation selectivity). Decreased serum leptin is known to be necessary for triggering energy-saving changes in V1 during food restriction. Consistent with this, we found significantly decreased serum leptin in food-restricted males but no significant change in food-restricted females. Collectively, our findings demonstrate that cortical function and energy usage in female mice are more resilient to food restriction than in males. The neocortex, therefore, contributes to sex-specific, energy-saving adaptations in response to metabolic challenge.

neuroscience↗

bioRxiv2019

Cerebellar-recipient motor thalamus drives behavioral context-specific movement initiation

To initiate goal-directed behavior, animals must transform sensory cues into motor commands that generate appropriately timed actions. Sensorimotor transformations along the cerebellar-thalamocortical pathway are thought to shape motor cortical output and movement timing, but whether this pathway initiates goal-directed movement remains poorly understood. Here, we recorded and perturbed activity in cerebellar-recipient regions of motor thalamus (dentate / interpositus nucleus-recipient regions, MThDN/IPN) and primary motor cortex (M1) in mice trained to execute a cued forelimb lever push task for reward. MThDN/IPN population responses were dominated by a time-locked increase in activity immediately prior to movement that was temporally uncoupled from cue presentation, providing a fixed latency feedforward motor timing signal to M1FL. Blocking MThDN/IPN output suppressed cued movement initiation. Stimulating the MThDN/IPN thalamocortical pathway in the absence of the cue recapitulated cue-evoked M1 membrane potential dynamics and forelimb behavior in the learned behavioral context, but generated semi-random movements in an altered behavioral context. Thus, cerebellar-recipient motor thalamocortical input to M1 is indispensable for the generation of motor commands that initiate goal-directed movement, refining our understanding of how the cerebellar-thalamocortical pathway contributes to movement timing.

neuroscience↗