A5011216805- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Photoreceptor and optogenetics research
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neural Engineering
- Neural dynamics and brain function
- Photochromic and Fluorescence Chemistry
- Receptor Mechanisms and Signaling
- Sleep and Wakefulness Research
- Advanced Fluorescence Microscopy Techniques
- Pluripotent Stem Cells Research
- Memory and Neural Mechanisms
- Advanced Memory and Neural Computing
- Neuroinflammation and Neurodegeneration Mechanisms
- Circadian rhythm and melatonin
- Neurogenesis and neuroplasticity mechanisms
- Ion channel regulation and function
- 3D Printing in Biomedical Research
- Anesthesia and Sedative Agents
- Sleep and related disorders
- Single-cell and spatial transcriptomics
- Phosphodiesterase function and regulation
- Marine Toxins and Detection Methods
- Tactile and Sensory Interactions
- Motor Control and Adaptation
Columbia University
2021-2024
Columbia University Irving Medical Center
2022-2024
Stanford University
2014-2022
New York Proton Center
2021
Center for Genomic Science
2021
Emory University
2009-2018
Zero to Three
2013
Cyclooxygenase-2 (COX-2), a source of inflammatory mediators and multifunctional neuronal modulator, is rapidly induced in select populations cortical neurons after status epilepticus. The consequences rapid activity-triggered induction COX-2 have been the subject much study speculation. To address this issue directly, we created mouse which conditionally ablated selected forebrain neurons. Results following pilocarpine-induced epilepticus indicate that promotes early neuroprotection then...
Summary Purpose Mutations in the voltage‐gated sodium channel (VGSC) gene SCN1A are responsible for a number of epilepsy disorders, including genetic with febrile seizures plus ( GEFS +) and D ravet syndrome. In addition to seizures, patients mutations often experience sleep abnormalities, suggesting that may also play role neuronal pathways involved regulation sleep. However, date, architecture has not been directly examined. To fill this gap, we tested hypothesis contributes architecture,...
We previously found that genetic mutants with reduced expression or activity of Scn8a are resistant to induced seizures and co-segregation a mutant allele can increase survival seizure resistance Scn1a mice. In contrast, is increased in the hippocampus following status epilepticus amygdala kindling. These findings point as promising therapeutic target for epilepsy raise possibility aberrant overexpression limbic structures may contribute some epilepsies, including temporal lobe epilepsy....
Understanding the neural mechanisms underlying sleep state transitions is a fundamental goal of neurobiology and important for development new treatments insomnia other disorders. Yet, brain circuits controlling this process remain poorly understood. Here we identify population sleep-active glutamatergic neurons in ventrolateral medulla (VLM) that project to preoptic area (POA), prominent sleep-promoting region, mice. Microendoscopic calcium imaging demonstrate these VLM display increased...
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Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution the ability track underlying membrane potential dynamics present across complex three-dimensional dendritic arbor vivo. Here, we perform fast two-photon imaging of somatic single pyramidal cells CA1 region mouse hippocampus during awake behavior. We study subthreshold suprathreshold events throughout vivo by combining voltage...
Mutations in the voltage-gated sodium channel gene SCN1A are responsible for a number of epilepsy disorders, including genetic with febrile seizures plus (GEFS+) and Dravet syndrome. In addition, dysfunction is increasingly being linked to neuropsychiatric abnormalities, social deficits cognitive disabilities. We have previously reported that mice heterozygous R1648H mutation identified GEFS+ family infrequent spontaneous seizures, increased susceptibility chemically hyperthermia-induced...
Abstract Here we report the pharmacologic blockade of voltage-gated sodium ion channels (Na V s) by a synthetic saxitoxin derivative affixed to photocleavable protecting group. We demonstrate that functionalized (STX-eac) enables exquisite spatiotemporal control Na s interrupt action potentials in dissociated neurons and nerve fiber bundles. The photo-uncaged inhibitor (STX-ea) is nanomolar potent, reversible binder s. use STX-eac reveal differential susceptibility myelinated unmyelinated...
Abstract Neuronal spiking activity is routinely recorded using genetically encoded calcium indicators (GECIs), but imaging limited in temporal resolution and does not report subthreshold voltage changes. Genetically (GEVIs) offer better sensitivity, spike detection with fast GEVIs has required specialized equipment. Here, we the ASAP4 subfamily of that brighten response to membrane depolarization, inverting fluorescence-voltage relationship previous ASAP GEVIs. Two variants, ASAP4b ASAP4e,...
Fast electrical signaling in dendrites is central to neural computations that support adaptive behaviors. Conventional techniques lack temporal and spatial resolution the ability track underlying membrane potential dynamics present across complex three-dimensional dendritic arbor vivo . Here, we perform fast two-photon imaging of somatic single pyramidal cells CA1 region mouse hippocampus during awake behavior. We study subthreshold suprathreshold events throughout by combining voltage with...
Despite nearly five decades of clinical use, a mechanistic description ketamine's ability to reliably produce anesthesia for surgery has been elusive. Ketamine is classified as "dissociative anesthetic" because it produces markedly distinct anesthetized state compared other anesthetic drugs. Furthermore, ketamine acts by increasing the high-frequency oscillations in beta-gamma range, which from γ-aminobutyric acid–mediated (GABAergic) anesthetics.1 was thought exert its effect acting...
Developmental and epileptic encephalopathies (DEE) are rare but devastating largely intractable childhood epilepsies. Genetic variants in ARHGEF9 , encoding a scaffolding protein important for the organization of postsynaptic density inhibitory synapses, associated with DEE accompanied by complex neurological phenotypes. In mouse model carrying patient-derived variant severe disease, we observed aggregation proteins loss functional synapses at axon initial segment (AIS), altered axo-axonic...
ABSTRACT Voltage-gated sodium channel (Na V ) activity underlies electrical signaling, synaptic release, circuit function, and, ultimately, behavior. Molecular tools that enable precise control of Na subpopulations make possible temporal regulation neuronal and cellular communication. To rapidly modulate currents, we have rendered a potent inhibitor, saxitoxin, transiently inert through chemical protection with novel nitrobenzyl-derived photocleavable group. Light-induced uncaging the...