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Katsanevaki, D.

Publications and source records attributed to Katsanevaki, D..

4 recordsLinked to original sources

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↗

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↗

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↗

Heterozygous deletion of SYNGAP enzymatic domains in rats causes selective learning, social and seizure phenotypes

Pathogenic variants in SYNGAP1 are one of the most common genetic causes of nonsyndromic intellectual disability (ID) and are considered a risk for autism spectrum disorder (ASD). SYNGAP1 encodes a synaptic GTPase activating protein that modulates the intrinsic GTPase activity of several small G-proteins and is implicated in regulating the composition of the postsynaptic density. By targeting the deletion of exons encoding the calcium/lipid binding (C2) and GTPase activating protein (GAP) domains, we generated a novel rat model to study SYNGAP related pathophysiology. We find that rats heterozygous for the C2/GAP domain deletion (Syngap+/{Delta}-GAP) exhibit reduced exploration and fear extinction, altered social behaviour, and spontaneous seizures, while homozygous mutants die within days after birth. This new rat model reveals that the enzymatic domains of SYNGAP are essential for normal brain function and provide an important new model system in the study of both ID/ASD and epilepsy.

neuroscience↗