A5079666245- Erythrocyte Function and Pathophysiology
- Ion channel regulation and function
- Pain Mechanisms and Treatments
- Neurobiology and Insect Physiology Research
- Neuropeptides and Animal Physiology
- Ion Channels and Receptors
- Chemical and Physical Studies
- Olfactory and Sensory Function Studies
- Biochemical Analysis and Sensing Techniques
- Cellular Mechanics and Interactions
- Neuroendocrine regulation and behavior
- Neuroscience and Neuropharmacology Research
- Child Nutrition and Feeding Issues
- Blood properties and coagulation
- Venomous Animal Envenomation and Studies
- Dermatology and Skin Diseases
- Neuroscience of respiration and sleep
- Nanopore and Nanochannel Transport Studies
- Hypothalamic control of reproductive hormones
- Tactile and Sensory Interactions
- Circadian rhythm and melatonin
- Lipid Membrane Structure and Behavior
- Muscle activation and electromyography studies
- Genetics and Physical Performance
- Cancer, Stress, Anesthesia, and Immune Response
National Institute of Neurological Disorders and Stroke
2020-2025
National Institutes of Health
2016-2025
National Center for Complementary and Integrative Health
2016-2025
University of California, Los Angeles
2024
University of California, San Francisco
2008-2012
University of San Francisco
2011
Czech Academy of Sciences, Institute of Physiology
2010
Columbia University
2004-2009
Amsterdam Nursing Home
2007
The heat and capsaicin receptor, TRPV1, is required for the detection of painful by primary afferent pain fibers (nociceptors), but extent to which functional TRPV1 channels are expressed in CNS debated. Because previous evidence based primarily on indirect physiological responses capsaicin, here we genetically modified Trpv1 locus reveal, with excellent sensitivity specificity, distribution all neuronal non-neuronal tissues. In contrast reports widespread robust expression CNS, find that...
The senses of touch and proprioception evoke a range perceptions rely on the ability to detect transduce mechanical force. molecular neural mechanisms underlying these sensory functions remain poorly defined. stretch-gated ion channel PIEZO2 has been shown be essential for aspects mechanosensation in model organisms.We performed whole-exome sequencing analysis two patients who had unique neuromuscular skeletal symptoms, including progressive scoliosis, that did not conform standard...
Primary afferent "pain" fibers (nociceptors) are divided into subclasses based on distinct molecular and anatomical features, these classes mediate noxious modality-specific contributions to behaviors evoked by painful stimuli. Whether the heat capsaicin receptor transient potential vanilloid-1 (TRPV1) is expressed heterogeneously across several sensory populations, or selectively a unique nociceptor subclass, however, unclear. Here we used two lines of <i>Trpv1</i> reporter mice investigate...
The stretch-gated ion channel PIEZO2 is required for inflammation-induced tactile allodynia.
The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence food and help digestion mechanically breaking down propelling gut content. Mechanical sensing thought to be essential for regulating motility; however, identity neuronal populations, molecules involved, functional consequences this sensation unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel motility. Piezo2 mouse dorsal root, but not nodose ganglia...
Classical migraine patients experience aura, which is transient neurological deficits associated with cortical spreading depression (CSD), preceding headache attacks. It not currently understood how a pathological event in cortex can affect peripheral sensory neurons. In this study, we show that cerebrospinal fluid (CSF) flows into the trigeminal ganglion, establishing nonsynaptic signaling between brain and cells. After CSD, ~11% of CSF proteome altered, up-regulation proteins directly...
Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception. Here, we discovered that extensively spliced, producing different isoforms with distinct properties. Sensory neurons from both mice humans express large repertoire of variants, whereas non-neuronal tissues predominantly single isoform. Notably, even within sensory ganglia, demonstrate the splicing to be cell type specific. Biophysical characterization revealed...
Itch is an unpleasant skin sensation that can be triggered by exposure to many chemicals, including those released mast cells. The natriuretic polypeptide b (Nppb)-expressing class of sensory neurons, when activated, elicits scratching responses in mice, but it unclear which itch-inducing agents stimulate these cells and the receptors involved. Here, we identify expressed Nppb neurons demonstrate functional importance as sensors endogenous pruritogens Our search for reveals they express...
The canonical view is that touch signaled by fast-conducting, thickly myelinated afferents, whereas pain slow-conducting, thinly ("fast" pain) or unmyelinated ("slow" afferents. While other mammals have afferents signaling (ultrafast nociceptors), these not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMRs) were insensitive to...
Painful stimuli evoke a mixture of sensations, negative emotions and behaviors. These myriad effects are thought to be produced by parallel ascending circuits working in combination. Here, we describe pathway from spinal cord brain for ongoing pain. Activation subset neurons expressing Tacr1 evokes full repertoire somatotopically directed pain-related behaviors the absence noxious input. projection (expressing NKR1) target tiny cluster superior lateral parabrachial nucleus (PBN-SL). We show...
Distal arthrogryposis (DA) is a collection of rare disorders that are characterized by congenital joint contractures. Most DA mutations in muscle- and joint-related genes, the anatomical defects originate cell-autonomously within musculoskeletal system. However, gain-of-function PIEZO2, principal mechanosensor somatosensation, cause subtype 5 (DA5) through unknown mechanisms. We show expression PIEZO2 mutation proprioceptive sensory neurons mainly innervate muscle spindles tendons sufficient...
Despite the potential importance of genital mechanosensation for sexual reproduction, little is known about how perineal touch influences mating. We explored affords exquisite awareness genitals and controls reproduction in mice humans. Using genetic strategies vivo functional imaging, we demonstrated that mechanosensitive ion channel PIEZO2 (piezo-type component 2) necessary behavioral sensitivity to touch. function needed triggering a touch-evoked erection reflex successful mating both...
The neuropeptides Substance P and CGRPα have long been thought important for pain sensation. Both peptides their receptors are expressed at high levels in pain-responsive neurons from the periphery to brain making them attractive therapeutic targets. However, drugs targeting these pathways individually did not relieve clinical trials. Since extensively co-expressed, we hypothesized that simultaneous inhibition would be required effective analgesia. We therefore generated Tac1 Calca double...
Several lines of evidence suggest that odorants are recognized through a combinatorial process in the olfactory system; single odorant is by multiple receptors and same receptor. However few details how this might actually function for any particular odour set or receptor family available. Approaching problem from ligands rather than receptors, we used response to common odorant, octanal, as basis defining profiles. Octanal other aldehydes induce large EOG responses rodent epithelium,...
The mammalian odorant receptors (ORs) comprise a large family of G protein-coupled that are critical determinants both the response profile and axonal identity olfactory sensory neurons in which they expressed. Although pathway by ORs activate odor transduction is well established, mechanism direct axons into proper glomerular relationships remains unknown. We have developed gain-of-function approach using injection retroviral vectors embryonic epithelium to study ORs' contribution axon...