posted on 2025-05-08, 22:12authored byMark A. Gradwell
The dorsal horn of the spinal cord is an integral site for the processing and transmission of sensory information. Our understanding of the neuronal populations within this region is, however, limited. This thesis builds upon two previous publications examining a population of, primarily inhibitory, interneurons within the dorsal horn identified by their expression of parvalbumin (PV). Initially, my group undertook a combined anatomical and electrophysiological approach to characterize these neurons. This work showed PV labels a distinct sub-population of inhibitory interneurons within the dorsal horn, as demonstrated by uniform morphology, intrinsic excitability, and excitatory input (Hughes et al. 2012). A key finding from this study was that PV⁺ axons often formed axoaxonic contacts with myelinated primary afferent fibres, an anatomical substrate for presynaptic inhibition. Following this initial characterization, another study demonstrated, through selective DREADD activation and saporin-mediated ablation studies, that PV⁺interneurons (PV⁺INs) play a crucial role in maintaining mechanical thresholds by ‘gating’ tactile information (Petitjean et al. 2015). This finding has far reaching impact, particularly in relation to the development of tactile allodynia (the percept of pain following innocuous stimulation). My work aims to bridge the gap between these two studies providing a cellular and circuit-based understanding of how PV⁺INs regulate sensory processing in the dorsal horn, as well as information that may allow future targeting of this population to relieve allodynia.