A5012180126- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Neuroscience and Neural Engineering
- Neural dynamics and brain function
- Sleep and Wakefulness Research
- Molecular Communication and Nanonetworks
- Memory and Neural Mechanisms
- Circadian rhythm and melatonin
- Biochemical Analysis and Sensing Techniques
- CRISPR and Genetic Engineering
- Regulation of Appetite and Obesity
- Neuroscience of respiration and sleep
- Ion channel regulation and function
- Neuroendocrine regulation and behavior
- Robot Manipulation and Learning
- Neonatal and fetal brain pathology
- Glaucoma and retinal disorders
- Genetics and Neurodevelopmental Disorders
- Veterinary Equine Medical Research
- Cerebral Venous Sinus Thrombosis
- Cardiac electrophysiology and arrhythmias
- Balance, Gait, and Falls Prevention
- Cell Image Analysis Techniques
- Motor Control and Adaptation
University of Michigan
2023-2025
University of Pennsylvania
2016-2022
Stanford University
2008-2021
Hospital of the University of Pennsylvania
2017
Bioengineering Center
2014
Yale University
2006-2008
Imperial College London
2008
Channelrhodopsin-2 (ChR2) has become an indispensable tool in neuroscience, allowing precise induction of action potentials with short light pulses. A limiting factor for many optophysiological experiments is the relatively small photocurrent induced by ChR2. We screened a large number ChR2 point mutants and discovered dramatic increase amplitude after threonine-to-cysteine substitution at position 159. When we tested T159C mutant hippocampal pyramidal neurons, could be very low intensities,...
Dravet syndrome (DS) is a neurodevelopmental disorder due to pathogenic variants in SCN1A encoding the Nav1.1 sodium channel subunit, characterized by treatment-resistant epilepsy, temperature-sensitive seizures, developmental delay/intellectual disability with features of autism spectrum disorder, and increased risk sudden death. Convergent data suggest hippocampal dentate gyrus (DG) pathology DS ( Scn1a +/- ) mice. We performed two-photon calcium imaging brain slice uncover profound...
Abstract In developmentally regulated D1:S3 splicing of Nav1.5, there are 31 nucleotide differences between the 5′‐exon (‘neonatal’) and 3′‐exon (‘adult’) forms, resulting in 7 amino acid D1:S3‐S3/S4 linker. particular, replaces a conserved negative aspartate residue ‘adult’ with positive lysine. Here, ‘neonatal’ Nav1.5 α‐subunit splice variants were stably transfected into EBNA‐293 cells their electrophysiological properties investigated by whole‐cell patch‐clamp recording. Compared...
Summary Objective In patients with temporal lobe epilepsy, seizures usually start in the hippocampus, and dentate granule cells are hyperexcitable. Somatostatin interneurons a major subpopulation of inhibitory neurons gyrus, many lost animal models. However, surviving somatostatin sprout axon collaterals form new synapses, so net effect on cell inhibition remains unclear. Methods The present study uses optogenetics to activate hilar measure gyrus perforant path–evoked local field potential...
Regulation of food intake and energy balance is critical to survival. Hunger develops as a response deficit drives food-seeking consumption. However, motivations eat are varied in nature, promoted by factors other than deficit. When dysregulated, non-homeostatic consume can contribute disorders intake, adding the increasing prevalence restrictive eating obesity. Melanin-concentrating hormone (MCH) neurons have been implicated regulation feeding behavior, addition number fundamental behaviors...
Hippocampal oscillations are critical for information processing, and strongly influenced by inputs from the medial septum. Hippocamposeptal neurons provide direct inhibitory feedback hippocampus onto septal cells, therefore likely to also play an important role in circuit; these fire at either low or high frequency, reflecting hippocampal network activity during theta ripple events, respectively. Here, we optogenetically target long-range GABAergic projection septum rats, thereby simulate...
The extracellular ionic environment in neural tissue has the capacity to influence, and be influenced by, natural bouts of activity. We employed optogenetic approaches control investigate these interactions within between cells, across spatial scales. began by developing a temporally precise means study microdomain-scale protons acid-sensing ion channels (ASICs). By coupling single-component proton-transporting tools ASICs create two-component constructs (TCOs), we found that acidification...
The lateral hypothalamus (LH), together with multiple neuromodulatory systems of the brain, such as dorsal raphe nucleus (DR), is implicated in arousal, yet interactions between these are just beginning to be explored. Using a combination viral tracing, circuit mapping, electrophysiological recordings from identified neurons, and combinatorial optogenetics mice, we show that GABAergic neurons LH selectively inhibit DR, resulting increased firing substantial fraction its ultimately promotes...
As the power of genetically encoded interventional and observational tools for neuroscience expands, boundaries experimental design are increasingly defined by limits in selectively expressing these relevant cell types. Single-recombinase-dependent expression systems have been widely used as a means to restrict gene based on single features combining recombinase-dependent viruses with recombinase-expressing transgenic animals. This protocol details how create INTRSECT constructs use multiple...
Major Vault Protein (MVP), the main constituent of vault ribonucleoprotein particle, is highly conserved in eukaryotic cells and upregulated a variety tumors. Vaults have been speculated to function as cargo transporters several cell lines, yet no work date has characterized protein neurons. Here we first describe cellular subcellular expression MVP primate rodent cerebral cortex, cortical neurons vitro. In prefrontal, somatosensory hippocampal cortices, was predominantly expressed pyramidal...
Impaired inhibition-and the resulting disruption of brain's excitatory-inhibitory (E-I) balance-has historically been theorized to play a critical role in epileptogenesis and seizures (Treiman, 2001).This concept is supported by numerous studies showing impaired function gamma-aminobutyric acid (GABA)-ergic both genetic acquired animal models epilepsy human epileptic brain tissue.Furthermore, medications that enhance GABAergic signaling have an anticonvulsant effect whereas GABA antagonists...
Objective Developmental and epileptic encephalopathies (DEEs) can result from dominant, gain of function variants neuronal ion channels. More than 450 de novo missense the sodium channel gene SCN8A have been identified in individuals with DEE. Methods We studied a mouse model carrying patient Scn8a variant p.Asn1768Asp. An AAV‐PHP.eB virus an allele‐specific single guide RNA (sgRNA) was administered by intracerebroventricular injection. Cas9 provided inherited transgene. Results...
Gain-of-function mutations in SCN8A cause developmental and epileptic encephalopathy (DEE), a disorder characterized by early-onset refractory seizures, deficits motor intellectual functions, increased risk of sudden unexpected death epilepsy. Altered activity neurons the corticohippocampal circuit has been reported mouse models DEE. We examined effect chronic seizures on gene expression hippocampus single-nucleus RNA sequencing mice expressing patient mutation SCN8A-p.Asn1768Asp (N1768D)....
Abstract Neocortical pyramidal cells (PYRs) receive synaptic inputs from many types of GABAergic interneurons. Connections between parvalbumin (PV)-positive, fast-spiking interneurons (“PV cells”) and PYRs are characterized by perisomatic synapses high-amplitude, short-latency IPSCs. Here, we present novel methods to study the functional influence PV on layer 5 using optogenetics combined with laser-scanning photostimulation (LSPS). First, examined strength spatial distribution PV-to-PYR...
Dravet syndrome (DS) is a severe neurodevelopmental disorder caused by pathogenic variants in the