A5037231861- Neuroendocrine regulation and behavior
- Sexual function and dysfunction studies
- Hypothalamic control of reproductive hormones
- Single-cell and spatial transcriptomics
- Neural dynamics and brain function
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genetics and Neurodevelopmental Disorders
- Memory and Neural Mechanisms
- RNA Research and Splicing
- Protease and Inhibitor Mechanisms
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- Knee injuries and reconstruction techniques
- Neurotransmitter Receptor Influence on Behavior
- Cell Image Analysis Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Heat shock proteins research
- Muscle Physiology and Disorders
- Sports injuries and prevention
- CRISPR and Genetic Engineering
- Orthopaedic implants and arthroplasty
- Exercise and Physiological Responses
- Neuroscience and Neuropharmacology Research
- Congenital heart defects research
University of Washington
2018-2025
Washington Center
2021-2024
Cold Spring Harbor Laboratory
2018-2024
Stony Brook University
2018-2024
Seattle University
2021
Allen Institute for Brain Science
2018-2021
Allen Institute
2018-2021
U.S. Army Research Institute of Environmental Medicine
2008-2011
United States Army
2008-2011
Georgia State University
2009
Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels cerebral cortex
The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution each cell type processes guided by essential for understanding its function in health and disease. We used transcriptomic epigenomic cortical taxonomies from mouse human define marker genes putative enhancers created a large toolkit transgenic lines enhancer AAVs selective targeting populations. report evaluation fifteen new driver lines, two reporter >800 different...
Studies using rodent models have shown that relapse to drug or food seeking increases progressively during abstinence, a behavioral phenomenon termed “incubation of craving.” Mechanistic studies incubation craving focused on specific neurobiological targets within preselected brain areas. Recent methodological advances in whole-brain immunohistochemistry, clearing, and imaging now allow unbiased brain-wide cellular resolution mapping regions circuits engaged learned behaviors. However, these...
Summary The rapid pace of cell type identification by new single-cell analysis methods has not been met with efficient experimental access to the newly discovered types. To enable flexible and specific neural populations in mouse cortex, we collected chromatin accessibility data from individual cells clustered identify enhancers for classes subclasses. When cloned into adeno-associated viruses (AAVs) delivered brain retro-orbital injections, these drive transgene expression subclasses...
Male ejaculation acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how affects and behavior female How the brain responds to completion of mating also unclear. Here, by using self-paced assay, we first demonstrate that mice show decreased after experiencing ejaculation. By brain-wide analysis activity-dependent labeling, next pinpointed medial preoptic area as a region strongly activated during post-ejaculatory period. Furthermore, freely moving...
Male ejaculation acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how affects and behavior female How the brain responds to completion of mating also unclear. Here, by using a self-paced assay, we first demonstrate that mice show decreased after experiencing ejaculation. By brain-wide analysis activity-dependent labeling, next pin-pointed medial preoptic area as region strongly activated during post-ejaculatory period. Furthermore, freely...
Summary Abstract Spatially integrated mechanisms of consciousness are unclear 1,2 . An approach to manipulate brainwide circuits regulating via synthetic central nervous system activation may pave the way for more precise transitions in and reveal underlying mechanisms. Toward this goal, we leverage anesthesia as a tool probe at cellular resolution within intact network. We perform chemogenetic capture 3,4 isoflurane anesthesia-activated circuitry mice —in parallel with electrocorticography...
The precise anatomical degree of brain X chromosome inactivation (XCI) that is sufficient to alter X-linked disorders in females unclear. Here, we quantify whole-brain XCI at single-cell resolution discover a prevalent activation ratio maternal paternal 60:40 across all divisions the adult brain. This modest, non-random influences disease penetrance: transmission fragile mental retardation 1 (Fmr1)-knockout (KO) allele confers 55% total cells with mutant X-active, which for behavioral...
High-throughput volumetric fluorescent microscopy pipelines can spatially integrate whole-brain structure and function at the foundational level of single cells. However, conventional protein (FP) modifications used to discriminate cells possess limited efficacy or are detrimental cellular health. Here, we introduce a synthetic nondeleterious nuclear localization signal (NLS) tag strategy, called “Arginine-rich NLS” (ArgiNLS), that optimizes genetic labeling downstream image segmentation by...
This study characterizes the temporal relationship of membrane type-1 matrix metalloproteinase (MT1-MMP) and tissue inhibitor metalloproteinase-2 (TIMP-2) expression in skeletal muscle following injury. Tibialis anterior (TA) muscles from 60 mice were exposed injured by applying a cold steel probe (−79°C) to for 10 s. Thereafter, TA uninjured legs collected at 3, 10, 24, 48, 72 h postinjury analysis local MT1-MMP, TIMP-2, metalloproteinases-2 -9 (MMP-2 MMP-9) mRNA protein content via...
ABSTRACT Diverse types of glutamatergic pyramidal neurons (PyNs) mediate the myriad processing streams and output channels cerebral cortex, yet all derive from neural progenitors embryonic dorsal telencephalon. Here, we establish genetic strategies tools for dissecting fate mapping PyN subpopulations based on their developmental molecular programs. We leverage key transcription factors effector genes to systematically target temporal patterning programs in differentiation postmitotic...
Abstract Ventral tegmental area (VTA) dopamine neurons regulate reward-related associative learning and reward-driven motivated behaviors, but how these processes are coordinated by distinct VTA neuronal subpopulations remains unresolved. Here we examine the neural correlates of prediction-error, action, cue, outcome encoding as well effort exertion reward anticipation during reward-seeking behaviors. We compare contribution two primarily dopaminergic largely non-overlapping subpopulations,...
The coupling and timing of pro- anti-inflammatory processes in skeletal muscle injury is poorly understood. We investigated the temporal response regulated extracellular signal-regulated kinases 1 2 (ERK1/2), p38, IkappaB kinase (IKK) α/β signaling pathways after traumatic injury.Traumatic freeze was delivered to tibialis anterior (TA) C57BL/6J mice, injured uninjured TA muscles were analyzed 3-72 h into recovery period.Significant increases pro-inflammatory cytokine transcription...
SUMMARY Male ejaculation acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how affects and behavior female How the brain responds to completion of mating also unclear. Here, by using self-paced assay, we first demonstrate that mice show decreased after experiencing ejaculation. By brain-wide analysis activity-dependent labeling, next pinpointed medial preoptic area as a region strongly activated during post-ejaculatory period. Furthermore,...
High-throughput volumetric fluorescent microscopy pipelines can spatially integrate whole-brain structure and function at the foundational level of single-cells. However, conventional protein (FP) modifications used to discriminate single-cells possess limited efficacy or are detrimental cellular health. Here, we introduce a synthetic non-deleterious nuclear localization signal (NLS) tag strategy, called 'Arginine-rich NLS' (ArgiNLS), that optimizes genetic labeling downstream image...
Non-random (skewed) X chromosome inactivation (XCI) in the female brain can ameliorate X-linked phenotypes, though clinical studies typically consider 80-90% skewing favoring healthy allele as necessary for this effect 1–10 . Here we quantify first time whole-brain XCI at single-cell resolution and discover a preferential of paternal to maternal ∼60:40 ratio, which surprisingly impacts disease penetrance. In Fragile-X-syndrome mouse model, Fmr1-KO transmitted maternally ∼60% cells causes but...
Myostatin (MSTN), a member of the transforming growth factor family, is involved in regulation skeletal muscle and development. Alterations MSTN system resulting inactivity or inhibition through binding proteins result enhanced protein synthesis excessive hypertrophy. Conversely, elevated expression unregulated activity are associated with sarcopenia catabolism. under constant inhibitory by several regulatory proteins, including follistatin-like related gene (FLRG) GDF-8 propeptide. PURPOSE:...
Abstract Studies using rodent models have shown that relapse to drug or food seeking increases progressively during abstinence, a phenomenon termed ‘incubation of craving’. Mechanistic studies incubation craving focused on specific neurobiological targets within pre- selected brain areas. Recent methodological advances in whole-brain immunohistochemistry, clearing, and imaging now enable unbiased brain-wide cellular resolution mapping regions circuits engaged learned behaviors. However,...