GABA distribution in a pain-modulating zone of trigeminal subnucleus interpolaris

Abstract

A recent model for control of spinal and medullary nociceptive neurons (Basbaum and Fields, 1984) incorporates a gamma-aminobutyric acid-ergic (GABA-ergic) cell into this circuitry and indicates that such elements could act as one substrate for presynaptic inhibition of primary afferents. This concept is supported by a variety of pharmacological and electrophysiological studies. We therefore examined the distribution of GABA-ergic activity in trigeminal subnucleus interpolaris (Vi) by focusing on the types of cells, together with dendritic and synaptic profiles, that are immunocytochemically labeled with an antiserum against glutamic acid decarboxylase (GAD). GAD occurred throughout Vi but was most concentrated in the ventrolateral quadrant and interstitial nucleus. It was localized to groups of small neurons with two to three primary dendrites, and within numerous punctate profiles suggestive of synaptic elements. Electron microscopy revealed labeled dendrites, some of which were postsynaptic to scalloped terminals of presumptive primary afferents. Other labeled dendritic elements, which were quite variable in size, engaged both GAD-labeled and unlabeled synapses. Most GAD synapses displayed clear round vesicles and formed contacts with unlabeled perikarya and a variety of dendritic processes. Numerous GAD-positive synapses were also incorporated into axoaxonic clusters, in which the GAD element was presynaptic to scalloped terminals. Others engaged in serial arrays with other unlabeled terminals, which, in turn, were presynaptic to dendrites. Occasionally, GAD synapses formed contacts with GAD-positive dendrites. These data show that GABA is localized to a variety of neuronal elements in ventrolateral Vi and the interstitial nucleus. These occur in spatial arrangements providing an anatomical substrate for postsynaptic modulation of activity in this area. GABA terminals also appear to be involved in a presynaptic inhibitory mechanism, which may, in some instances, affect transmission in primary afferents.