A5078768179- Neural dynamics and brain function
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Biomedical Text Mining and Ontologies
- Receptor Mechanisms and Signaling
- Sleep and Wakefulness Research
- Neurobiology and Insect Physiology Research
- Genetics and Neurodevelopmental Disorders
- EEG and Brain-Computer Interfaces
- Stress Responses and Cortisol
- Gene expression and cancer classification
- Olfactory and Sensory Function Studies
- stochastic dynamics and bifurcation
- Nicotinic Acetylcholine Receptors Study
- Sleep and related disorders
- Genetic Associations and Epidemiology
- RNA Research and Splicing
- Functional Brain Connectivity Studies
- Photoreceptor and optogenetics research
- Alzheimer's disease research and treatments
- Immune cells in cancer
Centre for Addiction and Mental Health
2017-2025
University of Toronto
2017-2025
Addiction Research Foundation
2022-2024
Canada Research Chairs
2019-2023
Rush University Medical Center
2022
Columbia University Irving Medical Center
2022
Institute of Medical Sciences
2019-2021
University of British Columbia
2014-2021
Canada's Michael Smith Genome Sciences Centre
2016-2020
McGill University
2020
Scientific reproducibility has been at the forefront of many news stories and there exist numerous initiatives to help address this problem. We posit that a contributor is simply lack specificity required enable adequate research reproducibility. In particular, inability uniquely identify resources, such as antibodies model organisms, makes it difficult or impossible reproduce experiments even where science otherwise sound. order better understand magnitude problem, we designed an experiment...
Genome-wide association studies (GWAS) have indicated moderate genetic overlap between Alzheimer's disease (AD) and related dementias (ADRD), Parkinson's (PD) amyotrophic lateral sclerosis (ALS), neurodegenerative disorders traditionally considered etiologically distinct. However, the specific variants loci underlying this remain almost entirely unknown.
Abstract Myelinated axons form long-range connections that enable rapid communication between distant brain regions, but how genetics governs the strength and organization of these remains unclear. We perform genome-wide association studies 206 structural connectivity measures derived from diffusion magnetic resonance imaging tractography 26,333 UK Biobank participants, each representing density myelinated within or a pair cortical networks, subcortical structures hemispheres. identify 30...
Establishing the molecular diversity of cell types is crucial for study nervous system. We compiled a cross-laboratory database mouse brain type-specific transcriptomes from 36 major across mammalian using rigorously curated published data pooled type microarray and single-cell RNA-sequencing (RNA-seq) studies. used these to identify marker genes, discovering substantial number novel markers, many which we validated computational experimental approaches. further demonstrate that summarized...
Cell-to-cell variability in molecular, genetic, and physiological features is increasingly recognized as a critical feature of complex biological systems, including the brain. Although such has potential advantages robustness reliability, how why circuits assemble heterogeneous cells into functional groups poorly understood. Here, we develop analytic approaches toward answering neuron-level variation intrinsic biophysical properties olfactory bulb mitral influences population coding...
Each down stroke of an insect’s wings accelerates axial airflow over the antennae. Modeling studies suggest that this can greatly enhance penetration air and air-born odorants through antennal sensilla thereby periodically increasing odorant-receptor interactions. Do these periodic changes result in entrainment neural responses antenna lobe (AL)? Does affect olfactory acuity? To address questions, we monitored AL moth Manduca sexta while were pulsed at frequencies from 10-72 Hz,...
The behavior of neural circuits is determined largely by the electrophysiological properties neurons they contain. Understanding relationships these requires ability to first identify and catalog each property. However, information about such locked away in decades closed-access journal articles with heterogeneous conventions for reporting results, making it difficult utilize underlying data. We solve this problem through NeuroElectro project: a Python library, RESTful API, web application...
Abstract In the human neocortex coherent interlaminar theta oscillations are driven by deep cortical layers, suggesting neurons in these layers exhibit distinct electrophysiological properties. To characterize this potential distinctiveness, we use vitro whole-cell recordings from 2 and 3 (L2&3), layer 3c (L3c) 5 (L5) of cortex. Across all observe notable heterogeneity, indicating pyramidal an electrophysiologically diverse population. L5 cells most excitable prominent sag current...
Cortical processing depends on finely tuned excitatory and inhibitory connections in neuronal microcircuits. Reduced inhibition by somatostatin-expressing interneurons is a key component of altered associated with treatment-resistant major depressive disorder (depression), which implicated cognitive deficits rumination, but the link remains to be better established mechanistically humans. Here we test effect reduced somatostatin interneuron-mediated cortical human microcircuits using...
Abstract Astrocytes, a type of glial cell in the central nervous system (CNS), adopt diverse states response to injury that are influenced by their location relative insult. Here, we describe platform for spatially resolved, single-cell transcriptomics and proteomics, called tDISCO ( tissue- digital microfluidic isolation single cells -Omics). We use alongside two high-throughput platforms spatial (Visium) (10X Chromium) examine heterogeneity astrocyte cortical ischemic stroke male mice....
For decades, neurophysiologists have characterized the biophysical properties of a rich diversity neuron types. However, identifying common features and computational roles shared across types is made more difficult by inconsistent conventions for collecting reporting data. Here, we leverage NeuroElectro, literature-based database electrophysiological ( www.neuroelectro.org ), to better understand neuronal diversity, both within types, confounding influences methodological variability. We...
How neuronal diversity emerges from complex patterns of gene expression remains poorly understood. Here we present an approach to understand electrophysiological through by integrating pooled- and single-cell transcriptomics with intracellular electrophysiology. Using neuroinformatics methods, compiled a brain-wide dataset 34 neuron types paired intrinsic features publically accessible sources, the largest such collection date. We identified 420 genes whose levels significantly correlated...
Abstract Cannabis is known to produce acute, transient psychotic-like experiences. However, it unclear whether cannabis disproportionately increases the risk of specific types psychotic experiences and genetic predisposition influences relationship between use In this cross-sectional study 109,308 UK Biobank participants, we examined how schizophrenia polygenic modulates association self-reported four (auditory hallucinations, visual persecutory delusions, delusions reference). Cohort-wide,...
Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement sleep at scale. Here, we aimed to examine the association accelerometer-derived measures with diagnoses polygenic scores in a large community-based cohort.In this post hoc cross-sectional analysis UK Biobank cohort, 10 interpretable measures-bedtime, wake-up time, duration, wake after onset, efficiency, number awakenings, duration longest...
Abstract N-methyl-D-aspartate receptors (NMDARs) are required to shape activity-dependent connections in the developing and adult brain. Impaired NMDAR signalling through genetic or environmental insults causes a constellation of neurodevelopmental disorders that manifest as intellectual disability, epilepsy, autism, schizophrenia. It is not clear whether developmental impacts dysfunction can be overcome by interventions adulthood. This question paramount for arising from mutations occur...
In order to further our understanding of how gene expression contributes key functional properties neurons, we combined publicly accessible expression, electrophysiology, and morphology measurements identify cross-cell type correlations between these data modalities. Building on previous work using a similar approach, distinguished which were "class-driven," meaning those that could be explained by differences excitatory inhibitory cell classes, reflected graded phenotypic within classes....
Cortical neuron loss is a pathological hallmark of late-onset Alzheimer’s disease (AD). However, it remains unclear which neuronal subtypes beyond broad excitatory and inhibitory classes are most vulnerable. Here, we analyzed cell subtype proportion differences in AD compared to non-AD controls using 1037 post-mortem brain samples from six neocortical regions. We identified the strongest associations with fewer somatostatin (SST) neurons (β = −0.48, p bonf 8.98 × 10 –9 ) intra-telencephalic...
Abstract Aging involves various neurobiological changes, although their effect on brain function in humans remains poorly understood. The growing availability of human neuronal and circuit data provides opportunities for uncovering age-dependent changes networks constraining models to predict consequences activity. Here we found increased sag voltage amplitude middle temporal gyrus layer 5 pyramidal neurons from older subjects captured this biophysical younger neurons. We used these simulate...
Attention depends on cholinergic excitation of prefrontal neurons but is sensitive to perturbation α5-containing nicotinic receptors encoded by Chrna5. However, Chrna5-expressing (Chrna5+) remain enigmatic, despite their potential as a target improve attention. Here, we generate complex transgenic mice probe Chrna5+ and sensitivity endogenous acetylcholine. Through opto-physiological experiments, discover that contain distinct population acetylcholine super-responders. Leveraging single-cell...
Abstract Changes in high-affinity nicotinic acetylcholine receptors are intricately connected to neuropathology Alzheimer’s Disease (AD). Protective and cognitive-enhancing roles for the α5 subunit have been identified, but this gene has not closely examined context of human aging dementia. Therefore, we investigate CHRNA5 impact relevant single nucleotide polymorphisms (SNPs) prefrontal cortex from 922 individuals with matched genotypic post-mortem RNA sequencing Religious Orders Study...