Mark A. Gradwell

ORCID: 0000-0003-3308-8005
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About
Contact & Profiles
Research Areas
  • Pain Mechanisms and Treatments
  • Neuroscience and Neuropharmacology Research
  • Neurobiology and Insect Physiology Research
  • Neural dynamics and brain function
  • Neuroscience and Neural Engineering
  • EEG and Brain-Computer Interfaces
  • Sleep and Wakefulness Research
  • Ion channel regulation and function
  • Myofascial pain diagnosis and treatment
  • Zebrafish Biomedical Research Applications
  • Anesthesia and Neurotoxicity Research
  • Botulinum Toxin and Related Neurological Disorders
  • Neuroendocrine regulation and behavior
  • Tactile and Sensory Interactions
  • Musculoskeletal pain and rehabilitation
  • Photoreceptor and optogenetics research
  • Stress Responses and Cortisol
  • Neurogenesis and neuroplasticity mechanisms
  • Neurotransmitter Receptor Influence on Behavior
  • Motor Control and Adaptation
  • Memory and Neural Mechanisms
  • Children's Physical and Motor Development
  • Transcranial Magnetic Stimulation Studies
  • Nerve injury and regeneration
  • Advanced Memory and Neural Computing

Rutgers, The State University of New Jersey
2021-2025

University of Newcastle Australia
2017-2023

Hunter Medical Research Institute
2017-2021

W. M. Keck Foundation
2021

Pleasurable touch is paramount during social behavior, including sexual encounters. However, the identity and precise role of sensory neurons that transduce remain unknown. A population labeled by developmental expression G protein-coupled receptor Mrgprb4 detects mechanical stimulation in mice. Here, we study relevance Mrgprb4-lineage reveal these are required for receptivity sufficient to induce dopamine release brain. Even isolation, optogenetic through back skin a conditioned place...

10.1016/j.cell.2022.12.034 article EN cc-by-nc Cell 2023-01-23

Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate passage information conveyed low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate polysynaptic relay LTMR input to inhibiting lamina II excitatory whose axons project into I. We changes...

10.1016/j.celrep.2019.06.040 article EN cc-by Cell Reports 2019-07-01

Nociceptive information is relayed through the spinal cord dorsal horn, a critical area in sensory processing. The neuronal circuits this region that underpin perception must be clarified to better understand how dysfunction can lead pathological pain. This study used an optogenetic approach selectively activate interneurons express calcium-binding protein calretinin (CR). We show these form interconnected network initiate and sustain enhanced excitatory signaling, directly relay signals...

10.7554/elife.49190 article EN cc-by eLife 2019-11-12

Abstract Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily laminae II inner and III. Inhibitory PVINs play an important role segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors postsynaptic distinct circuits. By comparison, relatively little is known excitatory (ePVINs) sensory processing. Here, we use neuroanatomical optogenetic approaches to show that ePVINs...

10.1097/j.pain.0000000000002422 article EN cc-by Pain 2021-07-28

The posterior medial (POm) thalamus is heavily interconnected with sensory and motor circuitry likely involved in behavioral modulation sensorimotor integration. POm provides axonal projections to the dorsal striatum, a hotspot of processing, yet role POm-striatal has remained undetermined. Using optogenetics slice electrophysiology, we found that robust synaptic input direct indirect pathway striatal spiny projection neurons (D1- D2-SPNs, respectively) parvalbumin-expressing fast spiking...

10.7554/elife.98563.2 preprint EN 2025-01-06

Abstract Projection neurons in the spinal dorsal horn relay sensory information to higher brain centres. The activation of these populations is shaped by afferent input from periphery, descending brain, and local interneuron circuits. Much our recent understanding circuitry comes studies transgenic mice; however, on projection still based largely monkey, cat, rat. We used viral labelling identify record mouse parabrachial nucleus (PBN) projecting located cord slices. Overall, lamina I...

10.1097/j.pain.0000000000002194 article EN cc-by Pain 2021-02-22

The superficial dorsal horn (SDH, LI-II) of the spinal cord receives and processes multimodal sensory information from skin, muscle, joints, viscera then relay it to brain. Neurons within SDH fall into two broad categories, projection neurons interneurons. later can be further subdivided excitatory inhibitory types. Traditionally, interneurons have been divided overlapping groups according their neurochemical, morphological electrophysiological properties. Recent clustering analyses, based...

10.3389/fnmol.2020.00032 article EN cc-by Frontiers in Molecular Neuroscience 2020-04-17

Unmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now source this synaptic input was not known. Here we provide evidence that it originates from a population inhibitory calretinin-expressing interneurons (iCRs), correspond to islet cells. The NP afferents can be assigned 3 functionally distinct classes (NP1-3). NP1 have been implicated pathological...

10.1038/s41598-023-38605-9 article EN cc-by Scientific Reports 2023-07-18

Key points Spinal parvalbumin‐expressing interneurons have been identified as a critical source of inhibition to regulate sensory thresholds by gating mechanical inputs in the dorsal horn. This study assessed inhibitory regulation interneurons, showing that synaptic and tonic glycinergic currents dominate, blocking neuronal or glial glycine transporters enhances currents, these manipulations reduce excitability. Synaptically released also enhanced resulted decreased interneuron Analysis...

10.1113/jp274926 article EN cc-by The Journal of Physiology 2017-09-14

Abstract Background Closed-loop behavior paradigms enable us to dissect the state-dependent neural circuits underlying in real-time. However, studying context-dependent locomotor perturbations has been challenging due limitations molecular tools and techniques for real-time manipulation of spinal cord circuits. New Method We developed a novel closed-loop optogenetic stimulation paradigm that utilizes DeepLabCut-Live pose estimation manipulate primary sensory afferent activity at specific...

10.1101/2024.07.28.605489 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2024-07-29

Spinal projection neurons (PNs) are defined by long axons that travel from their origin in the spinal cord to brain where they relay sensory information body. The existence and function of a substantial axon collateral network, also arising PNs remaining within cord, is less well appreciated. Here we use retrograde viral transduction strategy characterise novel subpopulation deep dorsal horn spinoparabrachial neurons. Brainbow assisted analysis confirmed virally labelled PN cell bodies...

10.1038/s41598-024-73620-4 article EN cc-by Scientific Reports 2024-11-01

Abstract Pleasurable touch during social behavior is the key to building familial bonds and meaningful connections. One form of occurs sexual encounters. Although initiated in part by touch, ongoing throughout copulation, identity role sensory neurons that transduce remain unknown. A population labeled G-protein coupled receptor Mrgprb4 detect stroking mice, however, these have never been implicated any natural behaviors. Here, we study relevance Mrgprb4-lineage genetically engineering mice...

10.1101/2021.09.22.461355 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2021-09-22

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading touch pain, known mechanical allodynia. Two main drivers peripheral information, mechanoreceptors (LTMRs) postsynaptic dorsal column neurons (PSDCs), terminate in brainstem nuclei (DCN). Activity within DRG, spinal cord, DCN have all been implicated mediating...

10.1101/2024.02.20.581208 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2024-02-23

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading touch pain, known mechanical allodynia. Two main drivers peripheral information, mechanoreceptors (LTMRs) postsynaptic dorsal column neurons (PSDCs), terminate in brainstem nuclei (DCN). Activity within DRG, spinal cord, DCN have all been implicated mediating...

10.2139/ssrn.4832224 preprint EN 2024-01-01

SUMMARY To achieve smooth motor performance in a changing sensory environment, outputs must be constantly updated response to feedback. Inhibitory interneurons the spinal cord play an essential role shaping activity by gating transmission of information and setting pattern rhythm neurons. Here, we identify medial deep dorsal horn as “hot zone” convergent proprioceptive cutaneous from hindlimb, where inhibitory neurons show increased responsiveness input are preferentially recruited during...

10.1101/2022.05.21.492933 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2022-05-21

Chronic pain presents a major unmet clinical problem. One of the most common symptoms chronic is tactile allodynia, where previously innocuous mechanical stimuli are perceived as painful. To help develop more effective analgesics to treat this condition, better understanding neuronal circuits underlying sensory perception in necessary. We have shown that inhibitory interneurons spinal dorsal horn express parvalbumin (PV) form axoaxonic synapses on central terminals low threshold...

10.2139/ssrn.3377640 article EN SSRN Electronic Journal 2019-01-01

<title>Abstract</title> Spinal projection neurons (PNs) are defined by long axons that travel from their origin in the spinal cord to brain where they relay sensory information body. The existence and function of a substantial axon collateral network, also arising PNs remaining within cord, is less well appreciated. Here we use retrograde viral transduction strategy characterise novel subpopulation deep dorsal horn spinoparabrachial neurons. Brainbow assisted analysis confirmed virally...

10.21203/rs.3.rs-3919064/v1 preprint EN cc-by Research Square (Research Square) 2024-02-21

Summary The posterior medial (POm) thalamus is heavily interconnected with sensory and motor circuitry likely involved in behavioral modulation sensorimotor integration. POm provides axonal projections to the dorsal striatum, a hotspot of processing, yet role POm-striatal has remained undetermined. Using optogenetics slice electrophysiology, we found that robust synaptic input direct indirect pathway striatal spiny projection neurons (D1- D2-SPNs, respectively) parvalbumin-expressing fast...

10.1101/2024.03.21.586152 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2024-03-27

The posterior medial (POm) thalamus is heavily interconnected with sensory and motor circuitry likely involved in behavioral modulation sensorimotor integration. POm provides axonal projections to the dorsal striatum, a hotspot of processing, yet role POm-striatal has remained undetermined. Using optogenetics slice electrophysiology, we found that robust synaptic input direct indirect pathway striatal spiny projection neurons (D1- D2-SPNs, respectively) parvalbumin-expressing fast spiking...

10.7554/elife.98563.1 preprint EN 2024-07-08
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