ORCID Profile
0000-0003-1260-3362
Current Organisations
University of Oxford
,
University of Glasgow
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Publisher: Wiley
Date: 27-08-2015
DOI: 10.1113/JP270855
Publisher: eLife Sciences Publications, Ltd
Date: 12-11-2019
DOI: 10.7554/ELIFE.49190
Abstract: Nociceptive information is relayed through the spinal cord dorsal horn, a critical area in sensory processing. The neuronal circuits in this region that underpin sensory perception must be clarified to better understand how dysfunction can lead to pathological pain. This study used an optogenetic approach to selectively activate spinal interneurons that express the calcium-binding protein calretinin (CR). We show that these interneurons form an interconnected network that can initiate and sustain enhanced excitatory signaling, and directly relay signals to lamina I projection neurons. Photoactivation of CR interneurons in vivo resulted in a significant nocifensive behavior that was morphine sensitive, caused a conditioned place aversion, and was enhanced by spared nerve injury. Furthermore, halorhodopsin-mediated inhibition of these interneurons elevated sensory thresholds. Our results suggest that dorsal horn circuits that involve excitatory CR neurons are important for the generation and lification of pain and identify these interneurons as a future analgesic target.
Publisher: Wiley
Date: 19-10-2017
DOI: 10.1113/JP274926
Publisher: Elsevier BV
Date: 10-2019
Publisher: Frontiers Media SA
Date: 2014
Publisher: Frontiers Media SA
Date: 17-04-2014
Publisher: Frontiers Media SA
Date: 06-02-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-07-2021
DOI: 10.1097/J.PAIN.0000000000002422
Abstract: Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs play an important role in segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here, we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported and that both ePVIN and inhibitory PVIN populations form synaptic connections among (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits and that aberrant activity of ePVINs under pathological conditions is well placed to contribute to the development of mechanical hypersensitivity.
Publisher: Elsevier BV
Date: 05-2013
Publisher: Wiley
Date: 12-11-2017
DOI: 10.1111/DEWB.12176
Publisher: American Physiological Society
Date: 11-2015
Abstract: The spinal cord is critical for modifying and relaying sensory information to, and motor commands from, higher centers in the central nervous system to initiate and maintain contextually relevant locomotor responses. Our understanding of how spinal sensorimotor circuits are established during in utero development is based largely on studies in rodents. In contrast, there is little functional data on the development of sensory and motor systems in humans. Here, we use patch-cl electrophysiology to examine the development of neuronal excitability in human fetal spinal cords (10–18 wk gestation WG). Transverse spinal cord slices (300 μm thick) were prepared, and recordings were made, from visualized neurons in either the ventral (VH) or dorsal horn (DH) at 32°C. Action potentials (APs) could be elicited in VH neurons throughout the period examined, but only after 16 WG in DH neurons. At this age, VH neurons discharged multiple APs, whereas most DH neurons discharged single APs. In addition, at 16–18 WG, VH neurons also displayed larger AP and after-hyperpolarization litudes than DH neurons. Between 10 and 18 WG, the intrinsic properties of VH neurons changed markedly, with input resistance decreasing and AP and after-hyperpolarization litudes increasing. These findings are consistent with the hypothesis that VH motor circuitry matures more rapidly than the DH circuits that are involved in processing tactile and nociceptive information.
Publisher: SAGE Publications
Date: 2014
Publisher: Wiley
Date: 08-2012
Publisher: Elsevier BV
Date: 06-2016
Publisher: eLife Sciences Publications, Ltd
Date: 03-10-2019
Publisher: Frontiers Media SA
Date: 21-08-2017
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David I Hughes.