Substance P-expressing excitatory interneurons in the mouse superficial dorsal horn provide a propriospinal input to the lateral spinal nucleus

Brain Struct Funct. 2018 Jun;223(5):2377-2392. doi: 10.1007/s00429-018-1629-x. Epub 2018 Mar 1.

Abstract

The superficial dorsal horn (laminae I and II) of the spinal cord contains numerous excitatory and inhibitory interneurons, and recent studies have shown that each of these groups can be divided into several neurochemically distinct populations. Although it has long been known that some neurons in this region have intersegmental (propriospinal) axonal projections, there have been conflicting reports concerning the number of propriospinal cells and the extent of their axons. In addition, little is known about the neurochemical phenotype of propriospinal neurons or about the termination pattern of their axons. In the present study we show, using retrograde tracing, that around a third of lamina I-II neurons in the lumbar enlargement project at least five segments cranially. Substance P-expressing excitatory neurons are over-represented among these cells, accounting for one-third of the propriospinal neurons. In contrast, inhibitory interneurons and excitatory PKCγ neurons are both under-represented among the retrogradely labelled cells. By combining viral vector-mediated Cre-dependent anterograde tracing with immunocytochemistry, we provide evidence that the lateral spinal nucleus (LSN), rather than the superficial dorsal horn, is the main target for axons belonging to propriospinal substance P-expressing neurons. These findings help to resolve the discrepancies between earlier studies and have implications for the role of the LSN in pain mechanisms.

Keywords: AAV; Intraspinal injection; Lamina II; Pain; Spinal cord; Tac1.

MeSH terms

  • Animals
  • Cholera Toxin / metabolism
  • Female
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Interneurons / physiology*
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Nerve Net / metabolism
  • PAX2 Transcription Factor / metabolism
  • Phosphopyruvate Hydratase / metabolism
  • Protein Kinase C / metabolism
  • Spinal Cord Dorsal Horn / cytology*
  • Substance P / metabolism*
  • Transduction, Genetic

Substances

  • PAX2 Transcription Factor
  • Pax2 protein, mouse
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Substance P
  • Cholera Toxin
  • protein kinase C gamma
  • Protein Kinase C
  • Phosphopyruvate Hydratase