A5051936553- Biochemical Analysis and Sensing Techniques
- Regulation of Appetite and Obesity
- Sex and Gender in Healthcare
- Genetics and Neurodevelopmental Disorders
- Adipose Tissue and Metabolism
- Congenital heart defects research
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Cellular transport and secretion
- Autism Spectrum Disorder Research
- Neural dynamics and brain function
- Alzheimer's disease research and treatments
- Dietary Effects on Health
- Memory and Neural Mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Visual perception and processing mechanisms
- Ubiquitin and proteasome pathways
- Genetic and Kidney Cyst Diseases
- Cardiovascular and Diving-Related Complications
- Nuclear Receptors and Signaling
- Lysosomal Storage Disorders Research
- Mitochondrial Function and Pathology
- Retinal and Macular Surgery
University of Edinburgh
2015-2024
Discovery Centre
2020-2024
Simons Foundation
2024
Wellcome/MRC Institute of Metabolic Science
2023
University of Cambridge
2023
Simons Initiative for the Developing Brain
2023
The potential for neuronal representations of external stimuli to be modified by previous experience is critical efficient sensory processing and improved behavioral outcomes. To investigate how repeated exposure a visual stimulus affects its representation in mouse primary cortex (V1), we performed two-photon calcium imaging layer 2/3 neurons assessed responses before, during, after the presentation repetitive over 5 consecutive days. We found stimulus-specific enhancement repetitively...
Recent advances in techniques for manipulating genomes have allowed the generation of transgenic animals other than mice. These new models enable cross-mammalian comparison neurological disease from core cellular pathophysiology to circuit and behavioural endophenotypes. Moreover they will us directly test whether common dysfunction or outcomes a genetic mutation are more conserved across species. Using rat model Fragile X Syndrome, we report that Fmr1 knockout (KO) rats exhibit elevated...
Information processing is energetically expensive. In the mammalian brain, it unclear how information coding and energy use are regulated during food scarcity. Using whole-cell recordings two-photon imaging in layer 2/3 mouse visual cortex, we found that restriction reduced AMPA receptor conductance, reducing synaptic ATP by 29%. Neuronal excitability was nonetheless preserved a compensatory increase input resistance depolarized resting potential. Consequently, neurons spiked at similar...
Mutations in SYNGAP1 are a common genetic cause of intellectual disability (ID) and risk factor for autism. encodes synaptic GTPase-activating protein (GAP) that has both signaling scaffolding roles. Most pathogenic variants predicted to result haploinsufficiency. However, some affected individuals carry missense mutations its calcium/lipid binding (C2) GAP domains, suggesting many clinical features from loss functions carried out by these domains. To test this hypothesis, we targeted the...
Previous studies have hypothesized that diverse genetic causes of intellectual disability (ID) and autism spectrum disorders (ASDs) converge on common cellular pathways. Testing this hypothesis requires detailed phenotypic analyses animal models with mutations accurately reflect those seen in the human condition (i.e., structural validity) which produce phenotypes mirror ID/ASDs face validity). We show SynGAP haploinsufficiency, ID co-occurring ASD humans, mimics occludes synaptic...
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), common monogenic cause intellectual disability autism, we investigated visual deficits. Syngap HET mice exhibited impaired discriminability, associated with reduced coding precision for stimuli the primary cortex (V1). Notably, intrinsic properties V1...
Abstract Pathogenic variants in SYNGAP1 are one of the most common genetic causes nonsyndromic intellectual disability (ID) and considered a risk for autism spectrum disorder (ASD). encodes syn aptic G TPase ctivating p rotein that modulates intrinsic GTPase activity several small G-proteins is implicated regulating composition postsynaptic density. By targeting deletion exons encoding calcium/lipid binding (C2) (GAP) domains, we generated novel rat model to study SYNGAP related...
Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts restriction, and such differ across sexes. Here, we examined restriction impacts function primary visual cortex (V1) adult male female mice. Molecular analysis RNA sequencing V1 revealed that males, but not females, significantly modulated canonical, energy-regulating pathways,...
Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts restriction, and such differ across sexes. Here, we examined restriction impacts function primary visual cortex (V1) adult male female mice. Molecular analysis RNA sequencing V1 revealed that males, but not females, significantly modulated canonical, energy-regulating pathways,...
Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts restriction, and such differ across sexes. Here, we examined restriction impacts function primary visual cortex (V1) adult male female mice. Molecular analysis RNA sequencing V1 revealed that males, but not females, significantly modulated canonical, energy-regulating pathways,...
Abstract Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts restriction, and such differ across sexes. Here, we examined restriction impacts function primary visual cortex (V1) adult male female mice. Molecular analysis RNA sequencing V1 revealed that males, but not females, significantly modulated canonical, energy-regulating...
Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts restriction, and such differ across sexes. Here, we examined restriction impacts function primary visual cortex (V1) adult male female mice. Molecular analysis RNA sequencing V1 revealed that males, but not females, significantly modulated canonical, energy-regulating pathways,...