A5073580285- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Hearing, Cochlea, Tinnitus, Genetics
- Epilepsy research and treatment
- Neural dynamics and brain function
- Neurotransmitter Receptor Influence on Behavior
- Ion channel regulation and function
- Noise Effects and Management
- Neonatal and fetal brain pathology
- Olfactory and Sensory Function Studies
- Memory and Neural Mechanisms
- Hearing Loss and Rehabilitation
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Acute Myeloid Leukemia Research
- Photoreceptor and optogenetics research
- Animal Vocal Communication and Behavior
- Ion Transport and Channel Regulation
- Traumatic Brain Injury and Neurovascular Disturbances
- Protein Degradation and Inhibitors
- RNA regulation and disease
- Acute Lymphoblastic Leukemia research
- Neurological disorders and treatments
- Pluripotent Stem Cells Research
The University of Texas at Austin
2017-2023
Wayne State University
2023
Dell Children's Medical Center of Central Texas
2022-2023
University of California, San Francisco
2013-2017
Neurological Surgery
2011-2017
University of Washington
2007-2010
Oregon Health & Science University
2000-2003
University of Miami
2002-2003
University of Colorado Health
2003
Proteins of the PSD-95-like membrane-associated guanylate kinase (PSD-MAGUK) family are vital for trafficking AMPA receptors (AMPARs) to synapses, a process necessary both basal synaptic transmission and forms plasticity. Synapse-associated protein 97 (SAP97) exhibits interactions, such as direct interaction with GluA1 AMPAR subunit, subcellular localization (synaptic, perisynaptic, dendritic) unique within this family. Due in part lethality germline knockout SAP97, protein's role plasticity...
The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and knockouts (CKOs), we defined their roles specific CINs. CKOs had dendritic, synaptic, survival defects, affecting even PV+ We provide evidence that DLX2 directly drives Gad1, Gad2, Vgat expression, show mutants reduced mIPSC amplitude. In addition, formed fewer GABAergic synapses on excitatory neurons frequency. Furthermore, Dlx1/2 CKO hypoplastic...
Objective A significant proportion of the more than 50 million people worldwide currently suffering with epilepsy are resistant to antiepileptic drugs (AEDs). As an alternative AEDs, novel therapies based on cell transplantation offer opportunity for long‐lasting modification epileptic circuits. To develop such a treatment requires careful preclinical studies in chronic model featuring unprovoked seizures, hippocampal histopathology, and behavioral comorbidities. Methods Transplantation...
Significance We describe homeostatic plasticity of both excitatory synaptic transmission and intrinsic properties CA1 pyramidal neurons in distal-less homeobox 1 ( Dlx1 −/− ) mice, a genetic model postdevelopment interneuron cell death. Loss inhibition compensation by excitation led to enhanced potential for long-term potentiation (LTP) altered neural oscillations. This shows that may rebalance but cannot fully normalize function. Transplantation progenitor cells restored inhibitory WT...
Mature nucleus magnocellularis (NM) neurons, the avian homolog of bushy cells mammalian anteroventral cochlear nucleus, maintain high [Cl − ] i and depolarize in response to GABA. Depolarizing GABAergic postsynaptic potentials (GPSPs) activate both synaptic conductance large outward currents, which, when coupled together, inhibit spikes via shunting spike threshold accommodation. We studied maturation voltage-dependent components inhibition embryonic NM neurons using whole-cell...
Neurons of the cochlear nuclei are anatomically and physiologically specialized to optimally encode temporal spectral information about sound stimuli, in part for binaural auditory processing. The avian nucleus magnocellularis (NM) integrates excitatory eighth nerve inputs depolarizing GABAergic inhibition such that fidelity is enhanced across synapse. biophysical mechanisms this inhibition, its role processing, not fully understood. We used whole-cell electrophysiology computational...
Object. Although the benefits of posttraumatic hypothermia have been reported in experimental studies, potential for therapeutic to increase intracerebral hemorrhage remains a clinical concern. The purpose this study was quantify amount extravasated hemoglobin after traumatic brain injury (TBI) and assess changes concentrations under hypothermic hyperthermic conditions. Methods. Intubated anesthetized rats were subjected fluid-percussion (FPI). In first experiment, divided into moderate...
Interneuron-based cell transplantation is a powerful method to modify network function in variety of neurological disorders, including epilepsy. Whether new interneurons integrate into native neural networks subtype-specific manner not well understood, and the therapeutic mechanisms underlying interneuron-based therapy, role synaptic inhibition, are debated. In this study, we tested integration transplanted using acute cortical brain slices visualized patch-clamp recordings measure...
Mutations of SCN1A, which encodes the voltage-gated sodium channel Nav1.1, can cause epilepsy disorders such as Dravet syndrome (DS) that are comorbid with wide-ranging neurologic dysfunction. Many studies suggest Nav1.1 haploinsufficiency causes forebrain GABAergic interneuron hypoexcitability, while pyramidal neuron physiology is mostly unaltered, and this serves a primary cell phenotype linking mutation to disease. We hypothesized deficits in inhibition would alter synaptic integration...
Myoclonus is characterized by sudden, brief involuntary movements, and its presence debilitating. We identified a family suffering from adult onset, cortical myoclonus without associated seizures. performed clinical, electrophysiological, genetic studies to define this phenotype.A large, 4-generation with history of underwent careful questioning, examination, electrophysiological testing. Thirty-five members donated blood samples for analysis, which included single nucleotide polymorphism...
Dlx transcription factors are important in the differentiation of GABAergic interneurons. In mice lacking Dlx1, early steps interneuron development appear normal. Beginning at ∼ 1 mo age, primarily dendrite-innervating subtypes begin to undergo apoptosis Dlx1(-/-) mice; this is accompanied by a reduction transmission and late-onset epilepsy. The reported synaptic inhibition greater than might be expected given that loss relatively modest mice. Here we report voltage-clamp recordings CA1...
Distortion-product otoacoustic emissions (DPOAEs) at 2f1-f2 can be suppressed by the introduction of a third “suppressor” tone. Plotting suppression DPOAE level against changing frequency and suppressor produces frequency-tuning functions referred to as tuning curves (STCs). The dominant features STCs, including their shape, are similar neural (NTCs) recorded from single auditory nerve fibers. However, recent findings using reversible diuretics suggest that STCs do not provide same measure...
Pathogenic variants in
Psychophysical, basilar-membrane (BM), and single nerve-fiber tuning curves, as well suppression of distortion-product otoacoustic emissions (DPOAEs), all give rise to frequency patterns with stereotypical features. Similarities differences between the behaviors these functions, both in normal conditions following various cochlear insults, have been documented. While neural curves (NTCs) BM behave similarly before after insults known disrupt selectivity, DPOAE (STCs) do not necessarily...
Loss of function variants
Mutations in the SCN1B gene have been linked to severe developmental epileptic encephalopathies including Dravet syndrome. Scn1b k nock o ut (KO) mice model loss of function disorders, demonstrating seizures, delays, and early death. encodes protein β1, an ion channel auxiliary subunit that also has roles cell adhesion, neurite outgrowth, expression. The goal this project is better understand how β1 alters information processing brain, resulting seizures associated cognitive dysfunction....