A5005307979- Neuroscience and Neuropharmacology Research
- Hearing, Cochlea, Tinnitus, Genetics
- Ion channel regulation and function
- Neural dynamics and brain function
- Trace Elements in Health
- Hearing Loss and Rehabilitation
- Electrochemical Analysis and Applications
- Cardiac electrophysiology and arrhythmias
- Advanced biosensing and bioanalysis techniques
- Neuroscience and Neural Engineering
- Biochemical Analysis and Sensing Techniques
- Advanced Memory and Neural Computing
- Vestibular and auditory disorders
- Molecular Sensors and Ion Detection
- RNA regulation and disease
- Memory and Neural Mechanisms
- Olfactory and Sensory Function Studies
- Ion Channels and Receptors
- Cellular transport and secretion
- Nicotinic Acetylcholine Receptors Study
- Signaling Pathways in Disease
- Neuroscience and Music Perception
- Multisensory perception and integration
- Heavy Metal Exposure and Toxicity
- Cannabis and Cannabinoid Research
University of Pittsburgh
2015-2024
Center for the Neural Basis of Cognition
2009-2024
Institute of Neurobiology
2011-2017
Institute for Neurodegenerative Disorders
2016
United States Nuclear Regulatory Commission
2016
Marine Biological Laboratory
2011-2015
Carnegie Mellon University
2012
University of Chicago
2011
Eye and Ear Foundation
2008
Google (United States)
2008
Tinnitus has been associated with increased spontaneous and evoked activity, neural synchrony, reorganization of tonotopic maps auditory nuclei. However, the neurotransmitter systems mediating these changes are poorly understood. Here, we developed an in vitro assay that allows us to evaluate roles excitation inhibition determining correlates tinnitus. To measure magnitude spatial spread circuit used flavoprotein autofluorescence (FA) imaging, a metabolic indicator neuronal activity. We...
Activity-dependent changes in neuronal excitability and synaptic strength are thought to underlie memory encoding. In hippocampal CA1 neurons, small conductance Ca2+-activated K+ (SK) channels contribute the afterhyperpolarization, affecting excitability. present study, we examined effect of apamin-sensitive SK on induction plasticity response a range stimulation frequencies. addition, role hippocampal-dependent encoding retention was also tested. The results show that blocking with apamin...
Tinnitus, the perception of phantom sound, is often a debilitating condition that affects many millions people. Little known, however, about molecules participate in induction tinnitus. In brain slices containing dorsal cochlear nucleus, we reveal tinnitus-specific increase spontaneous firing rate principal neurons (hyperactivity). This hyperactivity observed only noise-exposed mice develop tinnitus and nucleus regions are sensitive to high frequency sounds. We show reduction Kv7.2/3 channel...
Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic and glutamate are coreleased, it is controversial whether diffuses away from the release site or remains bound to presynaptic membranes proteins after its release. To study transmission quantify levels, we required a high-affinity rapid chelator as well an extracellular ratiometric fluorescent sensor. We demonstrate that tricine, considered preferred for studying role zinc, unable...
The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission implicated nearly all aspects brain development, function, and plasticity. Despite role AMPARs neurobiology, fine-tuning AMPA responses endogenous modulators remains poorly understood. Here we provide evidence that zinc, released single presynaptic action potentials, inhibits currents dorsal...
Voltage-gated Kv7 (KCNQ) channels are voltage-dependent potassium that activated at resting membrane potentials and therefore provide a powerful brake on neuronal excitability. Genetic or experience-dependent reduction of KCNQ2/3 channel activity is linked with disorders characterized by hyperexcitability, such as epilepsy tinnitus. Retigabine, small molecule activates KCNQ2-5 shifting their opening to more negative voltages, an US Food Drug Administration (FDA) approved anti-epileptic drug....
Cholinergic neuromodulation controls long-term synaptic plasticity underlying memory, learning, and adaptive sensory processing. However, the mechanistic interaction of cholinergic, neuromodulatory inputs with signaling pathways potentiation (LTP) depression (LTD) remains poorly understood. Here, we show that physiological activation muscarinic acetylcholine receptors (mAChRs) size sign associative via endocannabinoid signaling. Our findings indicate or pharmacological postsynaptic M1/M3...
Fluorescent sensors for mobile zinc are valuable studying complex biological systems. Because these typically bind rapidly and tightly, there has been little temporal control over the activity of probe after its application to a sample. The ability sensor in vivo during imaging experiments would greatly improve time resolution measurement. Here, we describe photoactivatable that can be triggered with short pulses UV light. These probes prepared by functionalizing protecting groups render...
Although it is well established that many glutamatergic neurons sequester Zn(2+) within their synaptic vesicles, the physiological significance of remains poorly understood. In experiments performed in a Zn(2+)-enriched auditory brainstem nucleus--the dorsal cochlear nucleus--we discovered and GPR39, putative metabotropic Zn(2+)-sensing receptor (mZnR), are necessary for triggering synthesis endocannabinoid 2-arachidonoylglycerol (2-AG). The postsynaptic production 2-AG, turn, inhibits...
Chelatable, or mobile, forms of zinc play critical signaling roles in numerous biological processes. Elucidating the action mobile Zn(II) complex environments requires sensitive tools for visualizing, tracking, and manipulating ions. A large toolbox synthetic photoinduced electron transfer (PET)-based fluorescent sensors are available, but applicability many these probes is limited by poor sensitivity low dynamic ranges owing to proton interference. We present here a general approach...
Vulnerability to noise-induced tinnitus is associated with increased spontaneous firing rate in dorsal cochlear nucleus principal neurons, fusiform cells. This hyperactivity caused, at least part, by decreased Kv7.2/3 (KCNQ2/3) potassium currents. However, the biophysical mechanisms underlying resilience tinnitus, which observed noise-exposed mice that do not develop (non-tinnitus mice), remain unknown. Our results show noise exposure induces, on average, a reduction KCNQ2/3 channel activity...
Presynaptic zinc release and a postsynaptic transporter organize into spatial functional microdomains.
Synaptic zinc ion (Zn2+) has emerged as a key neuromodulator in the brain. However, lack of research tools for directly tracking synaptic Zn2+ brain awake animals hinders our rigorous understanding physiological and pathological roles Zn2+. In this study, we developed genetically encoded far-red fluorescent indicator monitoring dynamics nervous system. Our engineered (FRISZ) displayed substantial Zn2+-specific turn-on response low-micromolar affinity. We anchored FRISZ to mammalian...
KQT-like subfamily (KCNQ) channels are voltage-gated, noninactivating potassium ion channels, and their down-regulation has been implicated in several hyperexcitability-related disorders, including epilepsy, neuropathic pain, tinnitus. Activators of these reduce the excitability central peripheral neurons, and, as such, have therapeutic utility. Here, we synthetically modified moieties KCNQ2-5 channel activator retigabine, an anticonvulsant approved by U.S. Food Drug Administration. By...
Damage to sensory organs triggers compensatory plasticity mechanisms in cortices. These result restored cortical responses, despite reduced peripheral input, and contribute the remarkable recovery of perceptual detection thresholds stimuli. Overall, damage is associated with a reduction GABAergic inhibition; however, less known about changes intrinsic properties underlying biophysical mechanisms. To study these mechanisms, we used model noise-induced male female mice. We uncovered rapid,...
Abstract Peripheral sensory organ damage leads to compensatory cortical plasticity that is associated with a remarkable recovery of responses sound. The precise mechanisms explain how this implemented and distributed over diverse collection excitatory inhibitory neurons remain unknown. After noise trauma persistent peripheral deficits, we found recovered sound-evoked activity in mouse A1 principal (PNs), parvalbumin- vasoactive intestinal peptide-expressing (PVs VIPs), but reduced...