A5028515965- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Lipid Membrane Structure and Behavior
- Autism Spectrum Disorder Research
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- Neural dynamics and brain function
- Mitochondrial Function and Pathology
- Congenital heart defects research
- Neuroscience and Neural Engineering
- Advanced Memory and Neural Computing
- Neurogenesis and neuroplasticity mechanisms
- Calcium signaling and nucleotide metabolism
- Advanced Fluorescence Microscopy Techniques
- Attention Deficit Hyperactivity Disorder
- Pancreatic function and diabetes
- Cognitive Functions and Memory
- RNA regulation and disease
- Nitric Oxide and Endothelin Effects
- Adipose Tissue and Metabolism
- Epigenetics and DNA Methylation
- Ion channel regulation and function
- Neuroendocrine regulation and behavior
- Sirtuins and Resveratrol in Medicine
- Alzheimer's disease research and treatments
Washington University in St. Louis
2015-2024
University of Missouri–St. Louis
2011-2024
University of Ottawa
2024
Hope Center for Neurological Disorders
2021-2022
Howard Hughes Medical Institute
2003-2008
Salk Institute for Biological Studies
2006-2008
University of Wisconsin–Madison
2000-2007
Peripheral sensory neurons regenerate their axon after nerve injury to enable functional recovery. Intrinsic mechanisms operating in are known regulate repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, contribute regeneration remains unexplored. Using a single cell RNAseq approach, we reveal that SGC distinct from Schwann and share similarities with astrocytes. Nerve elicits changes expression of genes related fatty acid synthesis peroxisome...
By examining many alternative arrangements of cortical areas, we have found that the arrangement actually present in brain minimizes volume axons required for interconnecting areas. Our observations support notion organization areas has evolved to optimize interareal connections.
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and leading genetic cause autism. It associated with lack fragile mental retardation protein (FMRP), a regulator synthesis in axons dendrites. Studies on FXS have extensively focused postsynaptic changes underlying dysfunctions long-term plasticity. In contrast, presynaptic mechanisms garnered relatively little attention are poorly understood. Activity-dependent processes give rise to several forms...
Significance Although loss of fragile X mental retardation protein 1 (FMRP) causes a wide range abnormalities in both pre- and postsynaptic compartments, the link between various FMRP functions specific phenotypes patients has been difficult to establish. Through study novel ( FMR1 ) missense mutation, c.413G > A (R138Q), recently identified patient with partial syndrome (FXS) phenotype (intellectual disability seizures), we found that are independent. Our findings suggest presynaptic,...
Short-term synaptic plasticity (STP) is an important mechanism for modifying neural circuits during computation. Although STP much studied, its role in the processing of complex natural spike patterns unknown. Here we analyze responses excitatory and inhibitory hippocampal synapses to trains at near-physiological temperatures. Our results show that express complementary sets components selectively change strength epochs high-frequency discharge associated with place fields. In both types...
Most voltage-gated Na+ channels inactivate almost completely at depolarized membrane potentials, but in some cells a residual current is seen that resistant to inactivation. This persistent can have profound impact on the electrical behavior of excitable cells, and regulation this property could important biological consequences. However, signaling mechanisms regulate persistence are not well understood. study showed nerve terminals ventricular myocytes nitric oxide (NO) reduced inactivation...
Short-term synaptic plasticity (STP) is widely thought to play an important role in information processing. This major function of STP has recently been challenged, however, by several computational studies indicating that transmission dynamic synapses broadband, i.e., frequency independent. Here we developed analytical approach quantify time- and rate-dependent transfer during arbitrary spike trains using a realistic model dynamics excitatory hippocampal synapses. We found indeed increases...
Single-channel recordings in CA3 pyramidal neurons revealed that large-conductance calcium-activated K(+) (BK) channel open probability was reduced by loss of fragile X mental retardation protein (FMRP) and FMRP acts on BK channels modulating the channel's gating kinetics. Fmr1/BKβ4 double knockout mice were generated to genetically upregulate activity absence FMRP. Deletion BKβ4 subunit alleviated via increasing frequency, but not through prolonging its duration. Genetic upregulation...
Altered neuronal excitability is one of the hallmarks fragile X syndrome (FXS), but mechanisms underlying this critical dysfunction are poorly understood. Here, we find that pyramidal cells in entorhinal cortex Fmr1 KO mice, an established FXS mouse model, display a decreased AP threshold and increased excitability. The changes mice caused by persistent sodium current (INaP). Our results indicate abnormal INaP animals mediated mGluR5-PLC-PKC (metabotropic glutamate receptor 5/phospholipase...
Studies of short-term plasticity (STP) in the hippocampus, performed mostly at room temperature, have shown that small central synapses rapidly depress response to high-frequency stimulation. This decrease synaptic strength with synapse use places constraints on STP as a dynamic filter for processing natural input. Here we report that, because strong but differential temperature dependence components, properties excitatory hippocampal change dramatically temperature. By separating...
Short-term plasticity (STP) comprises several rapid synaptic processes that operate on millisecond-to-minute timescales and modulate efficacy in an activity-dependent manner. Facilitation augmentation are two major STP components central synapses work to enhance strength, while various forms of short-term depression decrease it. These multiple interact perform a variety computations. Using modeling approach excitatory hippocampal synapses, we recently described the contributions individual...
Neuronal hyperexcitability is one of the major characteristics fragile X syndrome (FXS), yet molecular mechanisms this critical dysfunction remain poorly understood. Here we report a role voltage-independent potassium (K + )-channel in CA3 pyramidal neurons Fmr1 knock-out (KO) mice. We observed reduction small conductance calcium (Ca 2+ )-activated K (SK) currents both male and female mice, leading to decreased action potential (AP) threshold reduced medium afterhyperpolarization. These...
Vesicle sharing between synaptic boutons is an important component of the recycling process that synapses employ to maintain vesicle pools. However, mechanisms supporting and regulating transport during inter-synaptic exchange remain poorly understood. Using nanometer-resolution tracking individual vesicles advanced computational algorithms, we find long-distance axonal hippocampal partially mediated by actin network, with myosin V as primary actin-dependent motor drives this transport....
Synaptic vesicle fusion occurs at specialized release sites the active zone. How refilling of with new vesicles is regulated in central synapses remains poorly understood. Using nanoscale-resolution detection individual events rat hippocampal we found that inhibition myosin V, predominant vesicle-associated motor, strongly reduced during repetitive stimulation. Single-vesicle tracking revealed recycling continuously shuttle between a plasma membrane pool and an inner pool. Vesicle retention...
Glucose has long been considered a primary energy source for synaptic function. However, it remains unclear to what extent alternative fuels, such as lactate/pyruvate, contribute powering transmission. By detecting individual release events in hippocampal synapses, we find that mitochondrial ATP production regulates basal vesicle probability and location within the active zone (AZ), evoked by single action potentials. Mitochondrial inhibition shifts closer AZ center alters efficiency of...
Although Ca(2+)-signaling processes are thought to underlie many dendritic cell (DC) functions, the Ca(2+) entry pathways unknown. Therefore, we investigated in mouse myeloid DC using imaging and electrophysiological techniques. Neither currents nor changes intracellular were detected following membrane depolarization, ruling out presence of functional voltage-dependent channels. ATP, a purinergic receptor ligand, 1-4 dihydropyridines, previously suggested activate plasma channel human DC,...