A5052563417- Neuroscience and Neuropharmacology Research
- Cancer Genomics and Diagnostics
- Adipose Tissue and Metabolism
- Cancer Immunotherapy and Biomarkers
- Muscle Physiology and Disorders
- Ion channel regulation and function
- Immunotherapy and Immune Responses
- Vestibular and auditory disorders
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Lipid Membrane Structure and Behavior
- Cannabis and Cannabinoid Research
- CAR-T cell therapy research
- Hearing, Cochlea, Tinnitus, Genetics
- Ferroptosis and cancer prognosis
- Neurogenesis and neuroplasticity mechanisms
- Erythrocyte Function and Pathophysiology
- Genetic Neurodegenerative Diseases
- Nerve injury and regeneration
- Advanced Biosensing Techniques and Applications
- Cellular Mechanics and Interactions
- Neuroendocrine regulation and behavior
- CRISPR and Genetic Engineering
Personalis (United States)
2022-2024
Integrative Health Technologies (United States)
2024
The University of Texas Health Science Center at Houston
2024
Stanford University
2023
The University of Texas Health Science Center at San Antonio
2016-2022
Oregon Health & Science University
2009-2013
Vollum Institute
2009-2013
Northwestern University
2003-2008
Society for Neuroscience
2004
Neurons of the cerebellar nuclei receive synaptic excitation from mossy fibers. Unlike in many principal neurons, coincident presynaptic activity and postsynaptic depolarization do not generate long-term potentiation at these synapses. Instead, EPSCs are potentiated by high-frequency trains applied with hyperpolarization, patterns resembling mossy-fiber-mediated Purkinje-cell-mediated inhibition that predicted to occur during delay eyelid conditioning. Here, we have used electrophysiology Ca...
1010 Background: Circulating tumor DNA (ctDNA) based detection of Molecular Residual Disease (MRD) in breast cancer patients presents a strategy to identify at high risk relapse, although current assays have limited sensitivity for low level ctDNA detection. In this study we profile early with an ultra-sensitive, whole genome sequencing-based, tumor-informed platform, and correlate the findings clinical outcomes. Methods: We analysed 598 plasma samples (median 8 samples/patient, range 2-14)...
To date, the functions of most neural intermediate filament (IF) proteins have remained elusive. Peripherin is a type III protein that expressed in developing and differentiated neurons peripheral enteric nervous systems. It also major IF PC12 cells, widely used model for studies neurons. Dramatic increases peripherin expression been shown to coincide with initiation outgrowth axons during development regeneration, suggesting plays an important role axon formation. Recently, small...
We report that activation of GABA(A) receptors on cerebellar granule cell axons modulates both transmitter release and the excitability axon soma. Axonal depolarize axon, increasing its causing calcium influx at axonal varicosities. GABA-mediated subthreshold depolarizations in spread electrotonically to soma, promoting orthodromic action potential initiation. When chloride concentrations are unperturbed, GABA iontophoresis elicits spikes increases parallel fibers, indicating...
At a number of synapses, long-term potentiation (LTP) can be expressed by an increase in presynaptic strength, but it is unknown whether LTP solely through the probability that single vesicle released or multivesicular release (MVR). Here, we show decreases inhibition AMPA receptor EPSCs low-affinity antagonist at parallel fiber–molecular layer interneuron (PF–MLI) synapses. This indicates induction results larger glutamate concentration transients synaptic cleft, result indicative MVR, and...
Duchenne muscular dystrophy (DMD), the most common form of childhood dystrophy, is caused by mutations in dystrophin gene. In addition to debilitating muscle degeneration, patients display a range cognitive deficits thought result from loss normally expressed brain. While function tissue well characterized, its role brain still poorly understood. The highest expression mouse cerebellar Purkinje cells (PCs), where it colocalizes with GABA A receptor clusters. Using ex vivo...
Many excitatory synapses co-express presynaptic GABAA and GABAB receptors, despite their opposing actions on synaptic transmission. It is still unclear how co-activation of these receptors modulates synapse function. We measured GABA receptor function at parallel fibre onto stellate cells in the cerebellum using whole-cell patch-clamp recording photolytic uncaging RuBi-GABA. Activation results a transient (∼100 ms) enhancement transmission (mediated by receptors) followed long lasting (>500...
Previous studies of NMDA receptor (NMDAR) expression on axons cerebellar molecular layer interneurons have produced conflicting results. We made use the calcium sensitivity vesicular release machinery to test for NMDAR activity in basket cell axons. Iontophoresis l -aspartate, an agonist, onto axon collaterals had no effect evoked IPSCs measured synaptically coupled Purkinje cells. Furthermore, indicators varicosities did not report any change intracellular following iontophoresis -aspartate...
Abstract Parallel fiber synapses in the cerebellum express a wide range of presynaptic receptors. However, receptor expression at individual parallel is quite heterogeneous, suggesting physiological mechanisms regulate expression. We investigated changes GABA B receptors fiber‐stellate cell acute cerebellar slices from juvenile mice. receptor‐mediated inhibition excitatory postsynaptic currents (EPSCs) remarkably diverse these synapses, with transmitter release some inhibited by >50% and...
Signaling through the endocannabinoid system is critical to proper functioning of cerebellar circuit. However, most studies have focused on signaling cannabinoid type 1 (CB1) receptors, while relatively little known about 2 (CB2) receptors. We show that functional CB2 receptors are expressed in Purkinje cells using a combination immunohistochemistry and patch-clamp electrophysiology juvenile mice. Pharmacological activation significantly reduces inhibitory synaptic responses currents...
Duchenne muscular dystrophy (DMD) is generally regarded as a muscle-wasting disease. However, human patients and animal models of DMD also frequently display non-progressive cognitive deficits high comorbidity with neurodevelopmental disorders, suggesting impaired central processing. Previous studies have identified the cerebellar circuit, aberrant inhibitory transmission in Purkinje cells, particular, potential site dysfunction nervous system (CNS). In this work, we investigate output...
Axons can be depolarized by ionotropic receptors and transmit subthreshold depolarizations to the soma passive electrical spread. This raises possibility that axons axonal participate in integration firing neurons. Previously, we have shown exogenous GABA depolarizes cerebellar granule cell through local activation of A (GABA Rs) electrotonic spread potential resulting increased firing. We show here excitability cells is also release endogenous from molecular layer interneurons (MLIs)...
Unipolar brush cells (UBCs) are excitatory granular layer interneurons in the vestibulocerebellum. Here we assessed motor coordination and balance to investigate if deletion of acid-sensing ion channel 5 (Asic5), which is richly expressed type II UBCs, sufficient cause ataxia. The possible cellular mechanism underpinning ataxia this global Asic5 knockout model was elaborated using brain slice electrophysiology. impaired performance decreased intrinsic UBC excitability, reducing spontaneous...
Many synapses, including parallel fiber synapses in the cerebellum, express presynaptic GABA A receptors. However, reports of functional consequences receptor activation are variable across from inhibition to enhancement transmitter release. We find that function is bidirectional at depending on concentration and modulation receptors mice. Activation by low concentrations enhances glutamate release, whereas higher inhibits Furthermore, blocking B reduces currents shifts responses toward...
Abstract Many neurons, including cerebellar granule cells, exhibit a tonic GABA current mediated by extrasynaptic A receptors. This is critical regulator of firing and the target many clinically relevant compounds. Using combination patch clamp electrophysiology photolytic uncaging RuBi-GABA we show that B receptors are tonically active enhance receptor currents in cells. enhancement not associated with meaningful changes potency, mean channel open-time, open probability, or single-channel...
9562 Background: Detection of molecular residual disease (MRD) via circulating tumor DNA (ctDNA) can identify therapeutic response/resistance months in advance imaging, and monitoring clinically actionable variant dynamics ctDNA may be important for guiding treatment. Despite this, adoption has been slow due to the reduced sensitivity reproducibility current approaches. Here, we profile melanoma patients receiving ICI over several years using an ultra-sensitive, tumor-informed platform,...
Abstract Immune checkpoint inhibition (ICI) provides clinical benefit to a subset of cancer patients. Monitoring circulating tumor DNA (ctDNA) in peripheral blood may allow clinicians predict ICI response or resistance earlier than imaging and track more frequently. In this study, melanoma patients receiving were profiled using an ultra-sensitive, tumor-informed ctDNA detection platform, the findings correlated with outcome. retrospective 188 plasma samples collected from 23 advanced immune...
Abstract Monitoring clinically actionable and emerging mutations in circulating tumor DNA (ctDNA) may be crucial for guiding treatment, but adoption has been slow due to the narrow scope reproducibility of current approaches. Here, we investigate melanoma patients receiving ICI over several years, beginning with extensive mutational immune profiling followed by deep, whole-exome ctDNA monitoring.Here, 66 plasma samples from 23 advanced stage that were collected throughout treatment (up 40...
Exposure to nicotine in utero, often due maternal smoking, significantly elevates the risk of auditory processing deficits offspring. This study investigated effects chronic exposure during a critical developmental period on functional expression nicotinic acetylcholine receptors (nAChRs), glutamatergic synaptic transmission, and mouse brainstem. We evaluated functionality nAChRs at central synapse explored impact perinatal (PNE) currents brainstem responses (ABR) mice. Our findings revealed...
2510 Background: Determining which patients will achieve clinical benefit from immune checkpoint inhibition (ICI) therapy remains an open question. Liquid biopsy tests to assess baseline and early dynamics of circulating tumor DNA (ctDNA) may allow clinicians track response more granularly predict ICI or resistance prior imaging. However, lack sensitivity hinder accurate detection low ctDNA levels in tumors with shedding rates during substantial drops clearance response. Methods: This study...