Glutamatergic and GABAergic input to rat spinothalamic tract cells in the superficial dorsal horn

Abstract

The distribution of synaptic terminals onto spinothalamic tract cells (types I and II) of the superficial dorsal horn was determined with special reference to the amino acid transmitters glutamate and gamma-aminobutyric acid. Fifteen spinothalamic cells retrogradely labeled from the thalamus with the neuroanatomical tracer wheatgerm agglutinin conjugated to horseradish peroxidase were sectioned for electron microscopy. Serial sections from several levels through each cell were immunostained for glutamate and gamma-aminobutyric acid using a postembedding immunogold technique. Perimeter measurements of spinothalamic cell somata and dendrites and the lengths of apposition for all terminal profiles in contact with the spinothalamic cells were obtained from electron micrographs using a digitizing tablet. These data were used to determine the density of terminals on the soma and dendrites. In addition, the terminal population on these cells was categorized by transmitter content (glutamate, gamma-aminobutyric acid, or unlabeled). The results demonstrate that terminal density increased on dendrites relative to their distance from the soma. Glutamatergic and GABAergic input composed 37% and 20% of the terminal population, respectively, and these percentages remained uniform for the soma and dendrites. There were no significant differences among the 15 cells analyzed for this study. The results, therefore, suggest that both type I and type II STT cells of the superficial DH have similar synaptic organizations.

Synaptic Connections of the Neurokinin 1 Receptor-Like Immunoreactive Neurons in the Rat Medullary Dorsal Horn

“…There have been studies in the spinal dorsal horn showing synapses from axons containing GABA [45], norepinephrine [46] or 5-HT [47] on projection neurons in lamina I, however, our results have demonstrated that neurons with NK1 receptor-immunoreactivity received not only local GABAergic and Glycinergic inhibitory inputs from interneurons but also descending 5-HT- or NE-containing inputs from brainstem in laminae I, II and III of the MDH. The density of GABA-, Gly-, 5-HT- or DBH-LI terminals in contact with NK1 receptor-LI somata was different from the density of contacts on dendrites, and this may reflect functional differences.…”

Modeling effects of spinal cord stimulation on wide-dynamic range dorsal horn neurons: influence of stimulation frequency and GABAergic inhibition

“…This pattern of excitation followed by inhibition in dorsal horn neurons was replicated in experiments that measured the responses in unidentified dorsal horn neurons evoked by A-and C-fiber threshold stimulation (Woolf and King 1987;Woolf and Wall 1982). Finally, the dendrites of dorsal horn neurons receive both glutamatergic and GABAergic boutons (Alvarez et al 1993;Carlton et al 1992;Todd 2010), and these synapses appear to be distributed uniformly across the dendrites (Lekan and Carlton 1995). Taken together, these studies support the convergence of excitation and inhibition onto the model WDR neuron, and no prior computational model has reproduced this wide range of both excitatory and inhibitory phenomena.…”

“…Although representative of the appropriate spectrum of conduction velocities across a population of A␤, A␦, and C fibers, all primary afferent inputs to the IN and WDR neurons were located at the same dendritic segment. In reality, excitatory and inhibitory synapses are distributed throughout the dendritic arbors of these neurons (Lekan and Carlton 1995;Polgar et al 2010). However, randomizing the location of synaptic inputs from either the affer-ent inputs or the interneurons onto the WDR neurons did not appreciably affect the input-output characteristics of the network.…”

“…In contrast to the Aguiar (2010) model, no GABAergic synapses were implemented in the C fiber-to-WDR connection, as direct inhibitory connections between C fibers and projection neurons are rare (Alvarez et al 1993). Inhibitory and excitatory synapses were not segregated, as immunohistochemical studies have shown that inhibitory and excitatory synapses are uniformly distributed across the soma and dendrites of dorsal horn neurons (Lekan and Carlton 1995). Randomizing the locations of the A-fiber and C-fiber synaptic inputs onto the IN and WDR neurons as well as the synaptic connections between the IN and EX interneurons and the WDR neurons did not affect the input-output relationships of the network.…”

A possible role for glutamate receptor-mediated excitotoxicity in chronic pain

“…Lamina II is of particular interest, as the sensory input to this area is almost entirely C-fiber in nature. Most lamina II neurons are glutamatergic excitatory interneurons that relay inputs from primary afferents to lamina I projection neurons [8,9]. Other interneurons in laminae I and II contain inhibitory neurotransmitters gamma-amino butyric acid (GABA) [10], glycine, and enkephalin [10,11] and are a likely source of the inhibitory transmitters in terminals on projection neurons.…”