A5075019063- Neuroscience and Neuropharmacology Research
- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Viral Infections and Outbreaks Research
- Cell Image Analysis Techniques
- Nicotinic Acetylcholine Receptors Study
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Neural dynamics and brain function
- Virology and Viral Diseases
- Neurogenesis and neuroplasticity mechanisms
- Neurological disorders and treatments
- CRISPR and Genetic Engineering
- Genetic Syndromes and Imprinting
- Bioinformatics and Genomic Networks
- Virus-based gene therapy research
- Chromosomal and Genetic Variations
- Language and cultural evolution
- Bat Biology and Ecology Studies
- Genetic Associations and Epidemiology
- Genetic diversity and population structure
- Genetics and Neurodevelopmental Disorders
- Immune Response and Inflammation
Vollum Institute
2021-2024
Oregon Health & Science University
2021-2024
Harvard University
2011-2022
Broad Institute
2017-2021
Howard Hughes Medical Institute
2012-2016
University of Montana
2008-2015
Institute of Neurobiology
2011
Swarthmore College
2007
Female meiotic drive, in which paired chromosomes compete for access to the egg, is a potentially powerful but rarely documented evolutionary force. In interspecific monkeyflower (Mimulus) hybrids, driving M. guttatus allele (D) exhibits 98:2 transmission advantage via female meiosis. We show that extreme drive most likely caused by divergence centromere-associated repeat domains and document cytogenetic functional polymorphism within population of guttatus. conspecific crosses, D had 58:42...
Neurotransmitter corelease is emerging as a common theme of central neuromodulatory systems. Though glutamate or GABA with acetylcholine has been reported within the cholinergic system, full extent unknown. To explore synaptic signaling forebrain neurons, we activated choline acetyltransferase expressing neurons using channelrhodopsin while recording post-synaptic currents (PSCs) in layer 1 interneurons. Surprisingly, observed PSCs mediated by GABAA receptors addition to nicotinic receptors....
To understand how the nervous system processes information, a map of connections among neurons would be great benefit. Here we describe use vesicular stomatitis virus (VSV) for tracing neuronal in vivo. We made VSV vectors that used glycoprotein (G) genes from several other viruses. The G protein lymphocytic choriomeningitis endowed with ability to spread transsynaptically, specifically an anterograde direction, whereas rabies gave retrograde transsynaptic pattern. avian fusion allowed...
Understanding the organization of nervous system requires methods for dissecting contributions each component cell type to circuit function. One widely used approach combines genetic targeting Cre recombinase specific populations with infection recombinant adeno-associated viruses (rAAVs) whose transgene expression is activated by ("Cre-On"). Distinguishing how Cre-expressing neurons differ functionally from neighboring Cre-negative rAAVs that are inactivated ("Cre-Off") and can be in tandem...
The globus pallidus externus (GP) is a nucleus of the basal ganglia (BG), containing GABAergic projection neurons that arborize widely throughout BG, thalamus and cortex. Ongoing work seeks to map axonal patterns from GP cell types, as defined by their electrophysiological molecular properties. Here we use transgenic mice recombinant viruses characterize parvalbumin expressing (PV+) within BG circuit. We confirm PV+ 1) make up ~40% 2) exhibit fast-firing spontaneous activity 3) provide major...
The mouse cerebral cortex contains neurons that express choline acetyltransferase (ChAT) and are a potential local source of acetylcholine. However, the neurotransmitters released by cortical ChAT+ their synaptic connectivity unknown. We show nearly all in mice specialized VIP+ interneurons release GABA strongly onto other inhibitory acetylcholine sparsely layer 1 VIP+/ChAT+ interneurons. This differential transmission ACh based on postsynaptic target neuron is reflected interneuron...
Dopamine is released in the striatum during development and impacts activity of Protein Kinase A (PKA) striatal spiny projection neurons (SPNs). We examined whether dopaminergic neuromodulation regulates activity-dependent glutamatergic synapse formation developing striatum. Systemic vivo treatment with Gαs-coupled G-protein receptors (GPCRs) agonists enhanced excitatory synapses on direct pathway (dSPNs), whereas rapid production indirect (iSPNs) required activation Gαs GPCRs SPNs both...
The fundamental asymmetry of female meiosis creates an arena for genetic elements to compete inclusion in the egg, promoting selfish evolution centromere variants that maximize their transmission future egg. Such "female meiotic drive" has been hypothesized explain paradoxically complex and rapidly evolving nature centromeric DNA proteins. Although theoretically widespread, few cases active drive have observed, thereby limiting opportunities directly assess impact on molecular variation at...
ABSTRACT Primates and rodents, which descended from a common ancestor more than 90 million years ago, exhibit profound differences in behavior cognitive capacity. Modifications, specializations, innovations to brain cell types may have occurred along each lineage. We used Drop-seq profile RNA expression 184,000 individual telencephalic interneurons humans, macaques, marmosets, mice. Conserved interneuron varied significantly abundance between mice primates, but much modestly among primates....
Abstract Brain function depends on synaptic connections between specific neuron types, yet systematic descriptions of networks and their molecular properties are not readily available. Here, we introduce SBARRO ( S ynaptic B arcode A nalysis by R etrograde abies Read O ut), a method that uses single-cell RNA sequencing to reveal directional, monosynaptic relationships based the paths barcoded rabies virus from its “starter” postsynaptic cell cell’s presynaptic partners. Thousands these...
Defining the connections among neurons is critical to our understanding of structure and function nervous system. Recombinant viruses engineered transmit across synapses provide a powerful approach for dissection neuronal circuitry in vivo. We recently demonstrated that recombinant vesicular stomatitis virus (VSV) can be endowed with anterograde or retrograde synaptic tracing ability by providing different glycoproteins. Here we extend characterization transmission gene expression VSV rabies...
ABSTRACT Genetics can provide a systematic approach to discovering the tissues and cell types relevant for complex disease or trait. Identifying these is critical following up on non-coding allelic function, developing ex-vivo models, identifying therapeutic targets. Here, we analyze gene expression data from several sources, including GTEx PsychENCODE consortia, together with genome-wide association study (GWAS) summary statistics 48 diseases traits an average sample size of 169,331,...
Several databases have been compiled with the aim of documenting distribution typological features across world’s languages. This paper looks at ways utilizing this type data for making inferences concerning genealogical relationships by using phylogenetic algorithms originally developed biologists. The focus is on methodology, including how to assess stability individual and suitability different algorithms, as well enhance signals heuristic procedures identifying relationships. various...
The mammalian brain is composed of diverse, specialized cell populations, few which we fully understand. To more systematically ascertain and learn from cellular specializations in the brain, used Drop-seq to perform single-cell RNA sequencing 690,000 cells sampled nine regions adult mouse brain: frontal posterior cortex (156,000 99,000 cells, respectively), hippocampus (113,000), thalamus (89,000), cerebellum (26,000), all basal ganglia – striatum (77,000), globus pallidus externus/nucleus...