A5039339381- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Neuroendocrine regulation and behavior
- Epigenetics and DNA Methylation
- Receptor Mechanisms and Signaling
- Neonatal and fetal brain pathology
- Anesthesia and Neurotoxicity Research
- Memory and Neural Mechanisms
- Cellular transport and secretion
- Cognitive and developmental aspects of mathematical skills
- Neurotransmitter Receptor Influence on Behavior
- Reading and Literacy Development
- Cannabis and Cannabinoid Research
- Prenatal Substance Exposure Effects
- Renal and related cancers
- Neuroscience and Neural Engineering
- Congenital heart defects research
- Sleep and Wakefulness Research
- Genetic and Kidney Cyst Diseases
- Psychedelics and Drug Studies
- Grief, Bereavement, and Mental Health
- Genetics and Neurodevelopmental Disorders
- Obsessive-Compulsive Spectrum Disorders
Yale University
2023-2025
Biogen (United States)
2024
National Center for PTSD
2023
MIND Research Institute
2015-2022
Cornell University
2015-2022
Weill Cornell Medicine
2017-2022
University of Connecticut
2011-2015
Institute for Systems Biology
2015
Abstract Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this mostly limited to DNA methylation (5mC). hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD male cohort, integrating neuronal-specific 5mC 5hmC as well gene expression profiles from human postmortem orbitofrontal cortex (OUD = 12; non-OUD 26). Single locus methylomic analysis co-methylation...
The ability to induce targeted mutations in somatic cells developing organisms and then track the fates of those is a powerful approach both for studying neural development modeling human disease. CRISPR/Cas9 system allows such mutagenesis, we therefore tested it combination with piggyBac transposase lineage labeling neocortical progenitors genes linked neurodevelopmental disruptions tumor formation. We show that sgRNAs designed target PTEN successfully decreased expression, led neuronal...
Synchronous neuronal activity is a hallmark of the developing mouse primary somatosensory cortex. While patterns synchronous in cortical layer 2/3 have been well described, source robust still unknown. Using novel microprism preparation and vivo 2-photon imaging neonatal mice, we show that organized barrel columns across layers. Monosynaptic rabies tracing slice electrophysiology experiments reveal pyramidal neurons receive significant 5 inputs during first postnatal week, silencing synaptic...
Dyslexia is a complex neurodevelopmental disorder characterized by impaired reading ability despite normal intellect, and associated with specific difficulties in phonological rapid auditory processing (RAP), visual attention working memory. Genetic variants Doublecortin domain-containing protein 2 (DCDC2) have been dyslexia, impairments short-term/working The purpose of this study was to determine whether sensory behavioral can result directly from mutation the Dcdc2 gene mice. Several...
Abstract The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution woven the LC into wide-ranging neural circuits that influence functions as broad autonomic systems, stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility activity inherently similar species, furthermore age, sex, brain state similarly species. degree to which homogenous these factors, however, never...
Developmental reading disorder (RD) affects 5-10% of school aged children, with a heritability approximately 60%. Genetic association studies have identified several candidate RD susceptibility genes, including DCDC2; however, direct connection between the function these genes and cognitive or learning impairments remains unclear. Variants in DCDC2, member doublecortin family been associated humans ADHD Dcdc2 may play role neuronal migration rats. In this study, we examined effect mutation...
Variants in DCDC2 have been associated with reading disability humans, and targeted mutation of Dcdc2 mice causes impairments both learning sensory processing. In this study, we sought to determine whether affects functional synaptic circuitry neocortex. We found resulted elevated spontaneous evoked glutamate release from neurons somatosensory cortex. The probability was decreased wild-type level by acute application N-methyl-d-aspartate receptor (NMDAR) antagonists when postsynaptic NMDARs...
Neuronal activity profoundly shapes the maturation of developing neurons. However, technical limitations have hampered ability to capture progression patterns in genetically defined neuronal populations. This task is particularly daunting given substantial diversity pyramidal cells and interneurons neocortex. A hallmark development this participation network that regulates circuit assembly. Here, we describe detailed methodology on imaging cohorts longitudinally throughout postnatal stages...
Abstract Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses 1–4 . At the cellular level, psychedelics induce structural neural plasticity 5,6 , exemplified by drug-evoked growth and remodeling of dendritic spines in cortical pyramidal cells 7–9 A key question how these modifications map onto cell type-specific circuits to produce psychedelics’ behavioral actions 10 Here, we use vivo optical imaging, chemogenetic perturbation, electrophysiology...
Mild hypoxic-ischemic encephalopathy is common in neonates with no evidence-based therapies, and 30-40% of patients experience adverse outcomes. The nature progression mild injury poorly understood. Thus, we studied the evolution perinatal brain using longitudinal two-photon imaging transgenic fluorescent proteins as a novel readout neuronal viability activity at cellular resolution. In vitro, murine organotypic hippocampal cultures underwent 15-20 minutes oxygen-glucose deprivation. vivo,...
Abstract Animals must survive by foraging for food in an uncertain and dangerous world. Experimental tasks such as Pavlovian learning have yielded insights into how neural circuits balance these conflicting motivational drives. Neuromodulators play a fundamental role this process, enabling flexible switching between The question of neuromodulators synergistically encode state is thus to systems neuroscience, yet the interplay during naturalistic decision making are not fully understood....