A5063151170- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Advanced Fluorescence Microscopy Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neural Engineering
- Advanced Electron Microscopy Techniques and Applications
- Lipid Membrane Structure and Behavior
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Cellular transport and secretion
- Axon Guidance and Neuronal Signaling
- Advanced biosensing and bioanalysis techniques
- Advanced Biosensing Techniques and Applications
- Microfluidic and Bio-sensing Technologies
- Nanopore and Nanochannel Transport Studies
- Electrowetting and Microfluidic Technologies
- Nuclear Receptors and Signaling
- Retinal Development and Disorders
- Electrochemical Analysis and Applications
- Autism Spectrum Disorder Research
- Neurological Disease Mechanisms and Treatments
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
Stanford University
2014-2024
Stanford Medicine
2023
Carnegie Institution for Science
2005
Carnegie Department of Plant Biology
2005
Université de Montréal
1995-1999
Montreal Neurological Institute and Hospital
1997
McGill University
1997
Synapse loss correlates with a cognitive decline in Alzheimer's disease (AD), but whether this is caused by fibrillar deposits known as senile plaques or soluble oligomeric forms of amyloid beta (Abeta) controversial. By using array tomography, technique that combines ultrathin sectioning tissue immunofluorescence, allowing precise quantification small structures, such synapses, we have tested the hypothesis Abeta surrounding contributes to synapse mouse model AD. We find are surrounded halo...
Glutamate is the predominant excitatory neurotransmitter in mammalian brain. Once released, its rapid removal from synaptic cleft critical for preventing excitotoxicity and spillover to neighboring synapses. Despite consensus on role of glutamate normal disease physiology, technical issues limit our understanding metabolism intact cells. To monitor levels inside at surface living cells, genetically encoded nanosensors were developed. The fluorescent indicator protein (FLIPE) consists...
Myelin is best known for its role in increasing the conduction velocity and metabolic efficiency of long-range excitatory axons. Accordingly, myelin observed neocortical gray matter thought to mostly ensheath axons connecting subcortical regions distant cortical areas. Using independent analyses light electron microscopy data from mouse neocortex, we show that a surprisingly large fraction (half layer 2/3 quarter 4) ensheathes inhibitory neurons, specifically parvalbumin-positive basket...
The postnatal establishment of cortical connectivity was studied by estimating the number (numerical density, synapse-to-neuron ratio, and total number) overall synaptic population its distribution into gamma-aminobutyric acid (GABA)-immunopositive GABA-immunonegative contacts in developing rat somatosensory cortex. These numerical data were obtained using unbiased disector method combination with GABA postembedding immunocytochemistry. density both populations low early period (postnatal...
Synapses of the mammalian CNS are diverse in size, structure, molecular composition, and function. their myriad variations fundamental to neural circuit development, homeostasis, plasticity, memory storage. Unfortunately, quantitative analysis mapping brain's heterogeneous synapse populations has been limited by lack adequate single-synapse measurement methods. Electron microscopy (EM) is definitive means recognize measure individual synaptic contacts, but EM only abilities composition...
Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote repair phase recovery. This occurs days to months after onset and involves brain remapping plasticity within peri-infarct zone. Elucidating mechanisms this critical for development new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during was reported enhance functional recovery in mice suggesting plays an important function modulating...
Amphiphysin is a nerve terminal-enriched protein thought to function in synaptic vesicle endocytosis, part through Src homology 3 (SH3) domain-mediated interactions with dynamin and synaptojanin. Here, we report the characterization of novel amphiphysin isoform (termed II) that was identified search data base expressed sequence tags. Antibodies specific II recognize 90-kDa on Western blot brain-specific highly enriched terminals. Like (now referred as I), binds synaptojanin its SH3 domain....
The objective of this study was to examine the influence sensory experience on synaptic circuitry cortex. For purpose, quantitative distribution overall and gamma-aminobutyric acid (GABA) population contacts investigated in each layer somatosensory barrel field cortex rats which were deprived from birth by continuously removing rows whiskers. Whereas there no statistically significant changes population, number proportion GABA-immunopositive profoundly altered IV sensory-deprived animals....
Endophilin is a recently discovered src homology 3 domain-containing protein that major in vitro binding partner for synaptojanin. To further characterize endophilin, we generated an antipeptide antibody. enriched the brain, and immunofluorescence analysis reveals high concentration of synaptic terminals, where it colocalizes with In assays demonstrate endophilin binds through its domain to synaptojanin, immunoprecipitation antiendophilin antibody stably associated synaptojanin nerve...
Phosphatidylinositol 4,5-biphosphate (PIP2) has been implicated in a variety of cellular processes, including synaptic vesicle recycling. However, little is known about the spatial distribution this phospholipid neurons and its dynamics. In study, we have focused on these questions by transiently expressing phospholipase C (PLC)-delta1 pleckstrin homology (PH) domain fused to green fluorescent protein (GFP) cultured hippocampal neurons. This PH binds specifically with high affinity PIP2....
Background Proper function of the mammalian brain relies on establishment highly specific synaptic connections among billions neurons. To understand how complex neural circuits function, it is crucial to precisely describe neuronal connectivity and distributions synapses from individual Methods Findings In this study, we present a new genetic labeling method that expression presynaptic marker, synaptophysin-GFP (Syp-GFP) in neurons vivo. We assess reliability use analyze spatial patterning...
Pregabalin [<i>S</i>-[+]-3-isobutylGABA or (<i>S</i>)-3-(aminomethyl)-5-methylhexanoic acid, Lyrica] is an anticonvulsant and analgesic medication that both structurally pharmacologically related to gabapentin (Neurontin; Pfizer Inc., New York, NY). Previous studies have shown pregabalin reduces the release of neurotransmitters in several vitro preparations, although molecular details these effects are less clear. The present study was performed using living cultured rat hippocampal neurons...
Amphiphysin I and II are nerve terminal-enriched proteins thought to function in synaptic vesicle endocytosis. In addition a C-terminal SH3 domain, the contain highly conserved putative binding site numerous consensus phosphorylation sites. We now demonstrate that amphiphysin but not is phosphoprotein which undergoes dephosphorylation during terminal depolarization. Further, both interact with domain of endophilin, synaptically enriched protein implicated The interaction direct mediated...
Abstract Neurons undergo complex morphological changes during differentiation and in cases of plasticity. A major determinant cell morphology is the actin cytoskeleton, which neurons comprised two isoforms, non‐muscle γ‐ β‐actin. To better understand their respective roles plasticity, cellular subcellular localization was examined developing adult cerebellar cortex. It observed that γ‐actin expressed at a constant level throughout development, while β‐actin expression rapidly decreases with...
Most cellular processes are known to be strongly temperature dependent. Nevertheless, a large fraction of studies mammalian synaptic function have been and performed near room (i.e., at least 10°C below physiological temperature). Here, we examined the effects on presynaptic in primary cultures rat hippocampal neurons. FM dyes, VAMP (vesicle-associated membrane protein)-GFP (green fluorescent protein) transfection, HRP uptake were used quantify various aspects vesicle recycling. Our results...
Numerous types of inhibitory neurons sculpt the performance human neocortical circuits, with each type exhibiting a constellation subcellular phenotypic features in support its specialized functions. Axonal myelination has been absent among characteristics used to distinguish neuron types; fact, very little is known about myelinated axons neocortex. Here, using array tomography analyze samples neurosurgically excised neocortex, we show that originate predominantly from parvalbumin-containing...
Abstract Tissue slicing is at the core of many approaches to studying biological structures. Among modern volume electron microscopy (vEM) methods, array tomography (AT) based on serial ultramicrotomy, section collection onto solid support, imaging via light and/or scanning microscopy, and re-assembly images into a for analysis. While AT largely uses standard EM equipment, it provides several advantages, including long-term preservation sample compatibility with multi-scale multi-modal...