Jedi-1 deficiency increases sensory neuron excitability through a non-cell autonomous mechanism

• Published in: Scientific reports 2020-01, Vol.10 (1), p.1300-1300, Article 1300
• Main Authors: Trevisan, Alexandra J., Bauer, Mary Beth, Brindley, Rebecca L., Currie, Kevin P. M., Carter, Bruce D.
• Format: Article
• Language: English
• Subjects: 631/136; 631/136/142; 631/378; 631/378/1934; 631/378/2596; 631/378/2596/3921; 631/378/2620; 631/378/2620/410; 631/378/340; 631/378/3917; Action potential; Action Potentials; Animals; Apoptosis; Biomarkers; Capsaicin; Cell Line; Dorsal root ganglia; Electrophysiology; Endothelial cells; Excitability; Firing pattern; Ganglia, Spinal - cytology; Ganglia, Spinal - metabolism; Glial cells; Humanities and Social Sciences; Humans; Immunohistochemistry; Mice; Mice, Knockout; Mice, Transgenic; multidisciplinary; Nervous system; Neuroglia - metabolism; Neuroglia - ultrastructure; Neuronal-glial interactions; Neurons; Patch-Clamp Techniques; Phagocytes; Receptors, Cell Surface - deficiency; Rodents; Science; Science (multidisciplinary); Sensory neurons; Sensory Receptor Cells - metabolism; Sensory Receptor Cells - ultrastructure; Sodium channels (voltage-gated)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-57971-2

The dorsal root ganglia (DRG) house the primary afferent neurons responsible for somatosensation, including pain. We previously identified Jedi-1 (PEAR1/MEGF12) as a phagocytic receptor expressed by satellite glia in the DRG involved in clearing apoptotic neurons during development. Here, we further investigated the function of this receptor in vivo using Jedi-1 null mice. In addition to satellite glia, we found Jedi-1 expression in perineurial glia and endothelial cells, but not in sensory neurons. We did not detect any morphological or functional changes in the glial cells or vasculature of Jedi-1 knockout mice. Surprisingly, we did observe changes in DRG neuron activity. In neurons from Jedi-1 knockout (KO) mice, there was an increase in the fraction of capsaicin-sensitive cells relative to wild type (WT) controls. Patch-clamp electrophysiology revealed an increase in excitability, with a shift from phasic to tonic action potential firing patterns in KO neurons. We also found alterations in the properties of voltage-gated sodium channel currents in Jedi-1 null neurons. These results provide new insight into the expression pattern of Jedi-1 in the peripheral nervous system and indicate that loss of Jedi-1 alters DRG neuron activity indirectly through an intercellular interaction between non-neuronal cells and sensory neurons.