A population of large lamina I projection neurons with selective inhibitory input in rat spinal cord

Neuroscience. 2001;102(1):167-76. doi: 10.1016/s0306-4522(00)00445-0.

Abstract

Lamina I of the spinal dorsal horn contains a diverse mixture of neurons. Among these, a group of giant neurons (Waldeyer cells) has long been recognized. In this study we have used immunocytochemistry to characterize a population of Waldeyer cells which were identified by the presence of high levels of the glycine receptor-associated protein gephyrin on their cell bodies and proximal dendrites. Most of these cells (27/29) were retrogradely labelled after injection of cholera toxin B subunit into the parabrachial area, and the majority (26/30) expressed the protein product of immediate-early gene c-fos, Fos, following noxious stimulation. Unlike many lamina I projection neurons, these cells either lacked the neurokinin 1 receptor, or expressed it at a very low level. Most of the gephyrin puncta on the cells were adjacent to axons that contained glutamate decarboxylase (and were therefore presumably GABAergic), which suggests that the cells are under powerful inhibitory control. Only around 35% of the puncta were associated with axons that expressed the glycine transporter GLYT2 (a marker for glycinergic axons); however, the glycine receptor alpha1 subunit was present at all of the gephyrin puncta on these cells. The cells received synapses from axons that contained nitric oxide synthase, most of which were also GABAergic, and in some cases this input was so dense that it outlined the cell bodies and dendrites. The innervation by nitric oxide synthase-containing axons was selective for these cells, compared to other neurons in the dorsal horn. From the results of this study we suggest that the gephyrin-rich cells form a specific population of lamina I projection neurons which convey noxious information to the brain. These cells are under powerful inhibitory control, and the study provides further evidence that inhibitory circuits in the dorsal horn are organized in a specific manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Neutral*
  • Animals
  • Carrier Proteins / metabolism*
  • Cholera Toxin / pharmacology
  • Female
  • Glutamate Decarboxylase / metabolism
  • Glycine Plasma Membrane Transport Proteins
  • Immunohistochemistry
  • Male
  • Membrane Proteins / metabolism*
  • Microscopy, Electron
  • Neural Inhibition / physiology*
  • Neural Pathways / metabolism*
  • Neural Pathways / ultrastructure*
  • Nitric Oxide Synthase / metabolism
  • Pain / metabolism
  • Pain / physiopathology
  • Posterior Horn Cells / metabolism*
  • Posterior Horn Cells / ultrastructure*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptors, Glycine / metabolism
  • Receptors, Neurokinin-1 / metabolism
  • Synapses / metabolism*
  • Synapses / ultrastructure*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Amino Acid Transport Systems, Neutral
  • Carrier Proteins
  • Glycine Plasma Membrane Transport Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins c-fos
  • Receptors, Glycine
  • Receptors, Neurokinin-1
  • Slc6a5 protein, rat
  • gephyrin
  • glycine receptor alpha1
  • gamma-Aminobutyric Acid
  • Cholera Toxin
  • Nitric Oxide Synthase
  • Glutamate Decarboxylase