Light microscopic and ultrastructural analysis of GABA-immunoreactive profiles in the monkey spinal cord

It is hypothesized that terminals containing gamma-aminobutyric acid (GABA) participate in presynaptic inhibition of primary afferents. To date, few convincing GABA-immunoreactive (GABA-IR) axo-axonic synapses have been demonstrated in support of this theory. The goal of this study is to document the relationship between GABA-IR profiles and central terminals in glomerular complexes in lumbar cord of the monkey (Macaca fascicularis). In addition, the relationship between GABA-IR profiles and other neural elements are analyzed in order to better understand the processing of sensory input in the spinal cord. GABA-IR cell bodies were present in Lissauer's tract (LT) and in all laminae in the spinal gray matter except lamina IX. GABA-IR fibers and terminals were heavily concentrated in LT; laminae I, II, and III; and present in moderate concentration in the deeper laminae of the dorsal horn, ventral horn (especially in association with presumed motor neurons), and lamina X. Electron microscopic analysis confined to LT and laminae I, II, and III demonstrated GABA-IR cell bodies, dendrites, and myelinated and unmyelinated fibers. GABA-IR cell bodies received sparse synaptic input, some of which was immunoreactive for GABA. The majority of the synaptic input to GABA-IR neurons occurred at the dendritic level. Furthermore, the presence of numerous vesicle-containing GABA-IR dendrites making synaptic interactions indicated that GABA-IR dendrites also provided a major site of output. Two consistent arrangements were observed in laminae I-III concerning vesicle-containing GABA-IR dendrites: 1) they were often postsynaptic to central terminals and 2) they participated in reciprocal synapses. The majority of GABA-IR axon terminals observed contained round clear vesicles and varying numbers of dense core vesicles. Only on rare occasions were GABA-IR terminals with flattened vesicles observed. GABA-IR terminals were not observed as presynaptic elements in axo-axonic synapses; however, on some occasions, GABA-IR profiles presumed to be axon terminals were observed postsynaptic to large glomerular type terminals. Our findings suggest that a frequent synaptic arrangement exists in which primary afferent terminals relay sensory information into a GABAergic system for further processing. Furthermore, GABA-IR dendrites appear to be the major source of input and output for this inhibitory system. The implications of this GABAergic neurocircuitry are discussed in relation to the processing of sensory input in the superficial dorsal horn and in terms of mechanisms of primary afferent depolarization (PAD).