A5000618760- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Memory and Neural Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Photoreceptor and optogenetics research
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Lipid Membrane Structure and Behavior
- Cell Image Analysis Techniques
- Neuroendocrine regulation and behavior
- Receptor Mechanisms and Signaling
- Neural Networks and Applications
- Cellular transport and secretion
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Functional Brain Connectivity Studies
- EEG and Brain-Computer Interfaces
- Alzheimer's disease research and treatments
- Ion channel regulation and function
- Amyotrophic Lateral Sclerosis Research
- Visual perception and processing mechanisms
- Advanced Memory and Neural Computing
- Retinal Development and Disorders
- Molecular Communication and Nanonetworks
National Institute on Drug Abuse
2016-2025
Johns Hopkins Medicine
2006-2025
Johns Hopkins University
2015-2025
National Institutes of Health
2015-2024
Government of the United States of America
2023-2024
Triad National Security (United States)
2023
ORCID
2021
Jackson Laboratory
2010-2017
The University of Texas Health Science Center at San Antonio
2001-2016
Howard Hughes Medical Institute
2006-2011
PSD-95 is a major protein found in virtually all mature excitatory glutamatergic synapses the brain. Here, we have addressed role of controlling synapse function by generating and characterizing KO mouse. We that alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)subtype glutamate receptor (AMPAR)-mediated synaptic transmission was reduced these mice. Two-photon (2P) uncaging MNI-glutamate onto individual spines suggested decrease AMPAR mouse stems from an increase proportion...
Changes in surface trafficking of AMPA receptors play an important role synaptic plasticity. Phosphorylation the C terminus receptor (AMPAR) subunit glutamate 2 (GluR2) and binding GluR2 to PDZ [postsynaptic density-95/Discs large/zona occludens-1]-domain containing protein, protein interacting with kinase (PICK1), have been proposed NMDA dependent internalization GluR2. However, fate internalized after (NMDAR) activation is still unclear. Both recycling degradation NMDAR reported. Here, we...
Abstract Visualizing neural activity from deep brain regions in freely behaving animals through miniature fluorescent microscope (miniscope) systems is becoming more important for understanding encoding mechanisms underlying cognitive functions. Here we present our custom‐designed miniscope GRadient INdex (GRIN) lens system that enables simultaneously recording hundreds of neurons months. This article includes design, the surgical procedure GRIN implantation, mounting on head a mouse, and...
Cyclophilin D (CyPD) is thought to sensitize opening of the mitochondrial permeability transition pore (mPTP) based on findings that cyclosporin A (CsA), a pseudo-CyPD substrate, hyperpolarizes membrane potential (ΔΨ) and inhibits apoptosis. We provide evidence contrasts with this model. Using live cell imaging two photon microscopy, we report overexpression CyPD desensitizes HEK293 rat glioma C6 cells apoptotic stimuli. By site-directed mutagenesis compromises peptidyl-prolyl cis-trans...
The delivery of AMPA receptors to the plasma membrane is a critical step both for synaptic these and regulation transmission. To directly visualize fusion events transport vesicles containing receptor GluA2 subunit with we used pHluorin-tagged subunits total internal reflection fluorescence microscopy. We demonstrate that insertion requires NSF binding site within its intracellular cytoplasmic domain RNA editing Q/R in ion channel region plays key role insertion. Finally, show heteromeric...
Parkinson's disease causes the most profound loss of aldehyde dehydrogenase 1A1-positive (ALDH1A1+) nigrostriatal dopaminergic neuron (nDAN) subpopulation. The connectivity and functionality ALDH1A1+ nDANs, however, remain poorly understood. Here, we show in rodent brains that nDANs project predominantly to rostral dorsal striatum, from which they also receive monosynaptic inputs, indicating extensive reciprocal innervations with striatal spiny projection neurons (SPNs). Functionally,...
Significance In neurons most fast excitatory neurotransmission is mediated by AMPA receptors, which cluster at synapses primarily on dendritic spines. Fast synaptic inhibition largely GABA A inhibitory mainly the soma and shafts. It unclear how these receptors are segregated delivered to specific locations plasma membranes. Here we directly studied constitutive exocytosis of demonstrate that they initially sorted into different vesicles in Golgi apparatus inserted distinct domains membrane....
PSD-95/SAP90/DLG/ZO-1 (PDZ) domain-mediated protein–protein interactions play important roles in regulating AMPA receptor trafficking and neuronal plasticity. GRIP1 GRIP2 are homologous multi-PDZ domain-containing proteins that bind to the C-termini of AMPA-R GluA2 GluA3 subunits. Previous attempts determine cellular neurons have been complicated by nonspecific reagents, embryonic lethality conventional KO mice. To circumvent these issues we developed a conditional targeted deletion strategy...
Controlled, wireless neuromodulation using miniature implantable devices is a long-sought goal in neuroscience. It will allow many studies and treatments that are otherwise impractical. Recent demonstrate advances through optogenetics, but test animals typically tethered, severely limiting experimental possibilities. Existing nontethered optical stimulators either deliver light cranial window applications to superficial layers of the brain, not widely accessible due highly specialized...
Astrocytes play an essential role in the maintenance and protection of brain, which we reported was diminished with age. Here, demonstrate that activation a purinergic receptor (P2Y-R) signaling pathway, astrocytes, significantly increases resistance astrocytes neurons to oxidative stress. Interestingly, P2Y-R old increased their stress levels were comparable stimulated young astrocytes. enhanced neuroprotection blocked by oligomycin Xestospongin C, inhibitors ATP synthase inositol (1,4,5)...
Dopamine D₂ receptor (DRD2) is important for normal function of the brain reward circuit. Lower DRD2 in increases risk substance abuse, obesity, attention deficit/hyperactivity disorder, and depression. Moreover, target most antipsychotics currently use. It well known that dopamine-induced endocytosis its desensitization. However, it remains controversial whether recycled back to plasma membrane or targeted degradation following dopamine stimulation. Here, we used total internal reflection...