Inhibitory Interneurons That Express GFP in thePrP-GFPMouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets

Abstract

The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter. Previous reports suggested that PrP-GFP cells belonged to a single morphological class (central cells), received inputs exclusively from unmyelinated primary afferents, and had axons that remained in lamina II. However, we recently reported that the PrP-GFP cells expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been shown that nNOS-expressing cells are more diverse in their morphology and synaptic connections. We therefore used a combined electrophysiological, pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We provide evidence that they are morphologically diverse (corresponding to "unclassified" cells) and receive synaptic input from a variety of primary afferents, with convergence onto individual cells. We also show that their axons project into adjacent laminae and that they target putative projection neurons in lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is more complex than previously recognized, and suggests that they are likely to have several distinct roles in regulating the flow of somatosensory information through the dorsal horn.

Physiological Functions of the Cellular Prion Protein

“…Non-neural cells of the forebrain also stain for PrP C , including the endothelial cells in blood vessel walls (Adle-Biassette et al, 2006). Furthermore, PrP C expression has been reported in the PNS, including the dorsal and ventral root ganglia of the spinal cord (Tremblay et al, 2007; Peralta et al, 2012; Ganley et al, 2015), sensory and motor axons (Manson et al, 1992) and Schwann cells (Follet et al, 2002). Outside of the nervous system, PrP C expression has been detected in immune cells, including T-lymphocytes, natural killer cells and mast cells (Durig et al, 2000; Haddon et al, 2009), and also in multiple organs, including the heart, pancreas, intestine, spleen, liver, and kidneys (Peralta and Eyestone, 2009).…”

Origin of heterogeneous spiking patterns from continuously distributed ion channel densities: a computational study in spinal dorsal horn neurons

“…) or prion protein (Ganley et al . ). Of all the spiking patterns, phasic spiking tends to be the most promiscuous.…”

“…J Physiol 596.9 (Prescott & De Koninck, 2002) and in neurons defined by expression of calretinin (Smith et al 2015) or vesicular glutamate transporter type 2 (Punnakkal et al 2014). Conversely, neither single nor delayed spiking is commonly observed in inhibitory neurons defined by expression of parvalbumin (Hughes et al 2012) or prion protein (Ganley et al 2015). Of all the spiking patterns, phasic spiking tends to be the most promiscuous.…”

The Inhibitory Neuronal Circuit of Spinal Cord in Neuropathic Pain

“…Most vertical and radial cells are mainly excitatory interneurons (18). Furthermore, these cells also are inhibitory neurons (11,19). But Yasaka T et al (20) observed that radial cells were excitatory interneurons.…”

“…But Yasaka T et al (20) observed that radial cells were excitatory interneurons. Ganley RP et al found that islet neurons received monosynaptic excitatory inputs exclusively from C-afferents and primary-afferent-evoked GABAergic inhibitory inputs only from Aδ-fibres in lamina III (19). However, lamina III GABAergic inhibitory neurons is unlikely responsible for mechanical allodynia (21).…”