Synaptic interactions between GABA-immunoreactive profiles and the terminals of functionally defined myelinated nociceptors in the monkey and cat spinal cord

Abstract

This study analyzes the synaptic interactions between the central terminals of Aδ high threshold mechanoreceptors (Aδ HTMs) and GABA- immunoreactive profiles. Aδ HTM primary afferents from three monkeys and one cat were electrophysiologically identified and intracellularly labeled with HRP, and their terminal arborizations in laminae I and II of the sacrocaudal spinal cord were studied at the ultrastructural level. GABA-immunoreactive profiles in relation to Aδ HTM terminals were demonstrated using postembedding colloidal gold techniques. Monkey Aδ HTM terminals (n = 131) usually constituted the central element of synaptic glomeruli; they established large asymmetric synaptic contacts with 1-13 dendrites (modal value 2-4) and were surrounded by 0-6 peripheral axon terminals (modal value 2-3). The large majority (around 85%) of the peripheral axon terminals were GABA immunoreactive. They were found presynaptic to the Aδ HTM terminal and/or to dendrites postsynaptic to the primary afferent terminal. Furthermore, all peripheral axon terminals found presynaptic to the Aδ HTM terminals showed GABA immunoreactivity. Within a single Aδ HTM fiber, this synaptic arrangement was found in 20-60% of its boutons. In addition, 28% of the postsynaptic dendritic profiles displayed weak GABA immunoreactivity. Some of them contained vesicles; however, only in a few cases did we observe synapses between a GABA-immunoreactive vesicle-containing dendrite and a dendritic profile postsynaptic to an Aδ HTM terminal. Similar synaptology and interactions with GABA-immunoreactive profiles were displayed by the terminals of the single cat Aδ HTM fiber studied. Our data support the hypothesis that GABA-containing neurons use both presynaptic and/or postsynaptic mechanisms to exert a powerful control, presumably inhibitory, over the transmission of nociceptive information between Aδ HTM afferents and second-order neurons in monkey and cat spinal cord. Our results also imply that GABA may be released within the synaptic glomeruli formed by Aδ HTM terminals either by local dendrites or by axon terminals. We discuss the possibility that these GABAergic synapses can be driven by inputs from both primary afferents and/or descending systems to modulate the transmission of nociceptive sensory information.