A5073326281- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Pain Mechanisms and Treatments
- Memory and Neural Mechanisms
- Pluripotent Stem Cells Research
- Photoreceptor and optogenetics research
- Ion Transport and Channel Regulation
- Dermatology and Skin Diseases
- Microbial Inactivation Methods
- Ultrasound and Hyperthermia Applications
- Neurobiology and Insect Physiology Research
- Neuroscience and Neural Engineering
- Planarian Biology and Electrostimulation
- Stress Responses and Cortisol
- Polyomavirus and related diseases
- Advancements in Transdermal Drug Delivery
- Botulinum Toxin and Related Neurological Disorders
- Enzyme function and inhibition
- Molecular Communication and Nanonetworks
- Hearing, Cochlea, Tinnitus, Genetics
- Pain Management and Placebo Effect
- Transgenic Plants and Applications
- Adrenal Hormones and Disorders
- Lipid Membrane Structure and Behavior
- Ultrasound and Cavitation Phenomena
Columbia University Irving Medical Center
1998-2024
Columbia University
2006-2022
New York University
1998-2006
NYU Langone Health
1999
Marine Biological Laboratory
1998
Peripheral nerve lesions provoke apoptosis in the dorsal horn of spinal cord. The cause cell death, involvement neurons, and relevance for processing somatosensory information are controversial. Here, we demonstrate a mouse model sciatic injury that glutamate-induced neurodegeneration loss γ-aminobutyric acid (GABA)ergic interneurons superficial promote transition from acute to chronic neuropathic pain. Conditional deletion Grin1, essential subunit N-methyl-d-aspartate-type glutamate...
Significance Modulation of peripheral nervous system (PNS) activity has shown promise in treating a wide range diseases, from epilepsy to rheumatoid arthritis. Clinically, stimulation nerves is most commonly delivered through invasive and risk-laden surgical electrode placement. Noninvasive technologies for PNS modulation can both increase safety expand application various disease stages. Recent studies have revealed the therapeutic potential noninvasive neuromodulation brain circuits with...
NMDA receptors have the potential to produce complex activity-dependent regulation of transmitter release when localized presynaptically. In somatosensory system, been immunocytochemically detected on presynaptic terminals primary afferents, and these proposed drive substance P from central a subset nociceptors in spinal cord dorsal horn. Here we report that functional are indeed present at or near afferent fibers. Furthermore, show activation results an inhibition glutamate terminals. Some...
The superficial dorsal horn is the synaptic termination site for many peripheral sensory fibers of somatosensory system. A wide range modalities are represented by these fibers, including pain, itch, and temperature. Because involvement local inhibition in horn, specifically that mediated inhibitory amino acids GABA glycine, so important signal processing, we investigated regional control excitatory interneurons under conditions inflammation-induced mechanical allodynia. We found projection...
Significance Neuropathic pain affects nearly 10% of the US population, and yet current treatments with small-molecule drugs fail to adequately alleviate nociception often produce serious side effects. High-voltage-activated calcium channels (HVACCs) are membrane proteins that necessary for synaptic transmission in sensory neurons, inhibiting these is a proven method achieve analgesia. In this work, we used subcutaneous injection express genetically encoded molecule blocks HVACCs neurons...
Blockade of Ca2+-permeable AMPA receptors in the rat spinal cord diminishes development hyperalgesia and allodynia associated with peripheral injury. Cobalt uptake studies reveal that are expressed by some substance P receptor-expressing (NK1R+) neurons lamina I, as well other throughout superficial dorsal horn. Selective elimination NK1R+ I III/IV horn also suppresses allodynia. These observations raise possibility contribute to excitatory synaptic drive onto hyperalgesia. The first synapse...
We tested the hypothesis that extracellular membrane-bound carbonic anhydrase (CA) type IV is responsible for regulation of interstitial pH (pH(o)) transients in brain. Rat hippocampal slices were incubated phosphatidylinositol-specific phospholipase C (PI-PLC), which cleaves link CA to external face plasma membranes. Then evoked alkaline pH(o) shifts studied a recording chamber, using microelectrodes. Incubation fluid was saved later analysis. The ability buffer rapid load reduced markedly...
Spreading depression (SD) and related phenomena have been implicated in hypoxic-ischemic injury. In such settings, SD occurs the presence of marked extracellular acidosis. itself can also generate changes pH (pH o ), including a pronounced early alkaline shift. hippocampal slice model, we investigated effect interstitial acidosis on generation propagation CA1 stratum radiatum. addition, carbonic anhydrase inhibitor (benzolamide) was used to decrease buffering shift investigate its role...
The kinetics of activity-dependent, extracellular alkaline transients, and the buffering pH (pH e ), were studied in rat hippocampal slices using a fluorescein-dextran probe. Orthodromic stimuli generated transients ≤0.05 units that peaked 273 ± 26 ms decayed with half-time 508 43 ms. Inhibition carbonic anhydrase (ECA) benzolamide increased rate rise by 25%, doubled peak amplitude, prolonged decay three- to fourfold. slow allowed marked temporal summation, resulting severalfold increase...
Background: NMDA receptors expressed by spinal cord neurons in the superficial dorsal horn are involved development of chronic pain associated with inflammation and nerve injury. The has a complex still poorly understood circuitry that is mainly populated inhibitory excitatory interneurons. Little known about how receptor subunit composition, therefore pharmacology voltage dependence, varies neuronal cell type. typically composed two NR1 subunits four NR2 subunits, NR2A-2D. We took advantage...
Interstitial ionic shifts that accompany ouabain-induced spreading depression (SD) were studied in rat hippocampal and cortical slices the presence absence of extracellular Ca 2+ . A double-barreled ion-selective microelectrode specific for H + , K Na or was placed CA1 stratum radiatum midcortical layer. Superfusion 100 μM ouabain caused a rapid, negative, interstitial voltage shift (2–10 mV) after 3–5 min. The negativity accompanied by rapid alkaline transient followed prolonged acidosis....
<h2>Abstract</h2> A polyclonal antibody, raised against the squid (<i>Loligo pealei</i>) syntaxin I, inhibited Ca<sup>2+</sup>-dependent interaction of with synaptotagmin C2A domain <i>in vitro</i>. Presynaptic injection anti-<i>Loligo</i> IgG into giant synapse blocked synaptic transmission without affecting presynaptic action potential or voltage-gated calcium current responsible for transmitter release. Repetitive stimulation produced a gradual decrease in amplitude postsynaptic as block...
NMDA receptors are important elements in pain signaling the spinal cord dorsal horn. They heterotetramers typically composed of two NR1 and four NR2 subunits: NR2A-2D. Mice lacking specific subunits show deficits transmission yet subunit location remains unclear. We have combined electrophysiological pharmacological approaches to investigate composition functional expressed by lamina I, substance P receptor-expressing (NK1R+) neurons, as well NK1R- neurons. Under low Mg 2+ conditions (100...
Abstract Atopic dermatitis (AD), driven by interleukins (IL‐4/IL‐13), is a chronic inflammatory skin disease characterized intensive pruritus. However, it unclear how immune signaling and sensory response pathways cross talk with each other. We differentiated itch neuron‐like cells (ISNLCs) from iPSC lines. These ISNLCs displayed neural markers action potentials responded specifically to itch‐specific stimuli. expressed receptors specific for IL‐4/IL‐13 were activated directly the two...
Abstract The detection of mechanical qualities foodstuffs is essential for nutrient acquisition, evaluation food freshness, and bolus formation during mastication. However, the mechanisms through which mechanosensitive cells in oral cavity transmit information from periphery to brain are not well defined. We hypothesized Merkel cells, epithelial mechanoreceptors important pressure texture sensing skin, can be mechanically activated cavity. Using live‐cell calcium imaging, we recorded cell...
The type II isoform of carbonic anhydrase is abundant in astrocytes and oligodendroglia. To explore whether the expression required for interstitial activity, we studied extracellular pH transients hippocampal slices from mutant mice devoid wild-type littermates. Stimulation Schaffer collateral afferents evoked similar CA1 stratum pyramidale, consisting a predominant alkaline shift little or no subsequent acidosis. After 5-s stimulus trains at 10 Hz, shifts were not significantly different...
Endogenous pH shifts facilitate spreading depression by effect on NMDA receptors. Rapid extracellular alkalinizations accompany normal neuronal activity and have been implicated in the modulation of N-methyl-d-aspartate (NMDA) Particularly large alkaline transients also occur at onset (SD). To test whether these endogenous can modulate SD, shift was amplified using benzolamide, a poorly permeant inhibitor interstitial carbonic anhydrase. SD evoked microinjection 1.2 M KCl into CA1 stratum...