Synaptic complexes formed by functionally defined primary afferent units with fine myelinated fibers

Abstract

The individual fine myelinated fibers of cutaneous mechanical nociceptors and "D-hair" receptors were identified by electrophysiological recording with micropipette electrodes in cats and monkeys. Their intraspinal terminations were labeled by iontophoresing horseradish peroxidase intracellularly and subsequent diaminobenzidine histochemistry. These terminations were examined with light and electron microscopy to determine the nature and organization of their synaptic contacts. Myelinated fibers of the mechanical nociceptors became unmyelinated before exhibiting many enlargements that made multiple synaptic contacts in the marginal zone (lamina I) and lamina V. Pre- or postsynaptic contacts were found only on enlargements. In the marginal zone of the cat, enlargements made simple axodendritic contacts or were scalloped, central terminals in glomeruli. In glomeruli, myelinated mechanical nociceptor enlargements were presynaptic to several dendritic appendages and postsynaptic to two different types of profiles. One type was interpreted as a presynaptic axon terminal, the other as a presynaptic, vesicle-containing, dendritic appendage. In lamina V of the cat the nociceptor synaptic complexes were similar, but simpler, and only axonal profiles were found to be presynaptic to them. In the monkey marginal zone and deep nucleus proprius, myelinated nociceptor terminations formed the central element of glomeruli, which consisted of postsynaptic dendritic appendages and presynaptic axon terminals. D-hair axons terminated in large numbers of enlargements in the nucleus proprius (laminae III and IV) and inner substantia gelatinosa (lamina IIi). Their large rounded enlargements formed the central terminals in glomeruli and were presynaptic to both ordinary and vesicle-containing dendritic appendages; the presynaptic dendritic profiles also often contacted each other. Profiles interpreted as axonal in origin were the only terminals presynaptic to the primary ending within the D-hair glomeruli. The results suggest that transfer of primary afferent information occurs only at enlargements of the primary fiber and that each primary fiber enters into more than one kind of synaptic arrangement. They also point out that synaptic glomeruli are common to functionally different types of primary afferent fibers and that the internal organization of glomeruli varies with the kind of primary fiber and the locus of the complex.

The Sensory Neurons of Touch

“…Aβ-LTMRs tend to form simpler synaptic arrangements with much fewer axoaxonic synapses, while Aδ-LTMRs tend to display many more axoaxonic structures that resemble type II synaptic glomeruli (Rethelyi et al, 1982, 1989). Although the ultrastructural appearance of C-LTMRs is not yet known, it is possible that they resemble synaptic arrangements of other C fibers.…”

“…Although the ultrastructural appearance of C-LTMRs is not yet known, it is possible that they resemble synaptic arrangements of other C fibers. However, like Aδ- and Aβ-LTMRs, C-fiber synaptic arrangement can be mixed, with non-peptidergic C-fibers displaying complex structures with many axoaxonic synapses similar to type I synaptic glomeruli, while peptidergic afferents form much simpler synaptic arrangements (Rethelyi et al, 1982; Ribeiro-da-Silva et al, 1989b). Thus, it is likely that presynaptic inhibitory inputs to different LTMR subtypes originate from specific types of interneurons, but the identity of such populations remains elusive.…”

Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia

“…Most studies on spinal inhibition focus on postsynaptic inhibition, involving the release of GABA and/or glycine at axodendritic and/or axosomatic synapses, but GABA release at axoaxonic synapses is also known to mediate presynaptic inhibition of primary afferent central terminals. Although axoaxonic synapses have been described on the central terminals of most types of primary afferents (Réthelyi et al., 1982, Ribeiro-da-Silva and Coimbra, 1982, Todd, 1996, Hughes et al., 2005) and a high incidence of such synaptic connections has been reported in lamina II (Duncan and Morales, 1978), identifying the cells that give rise to these synapses has proven challenging. We have demonstrated that a significant proportion of axoaxonic synapses on the central terminals of myelinated afferents are derived from inhibitory interneurons that express the calcium-binding protein parvalbumin (PV), and that axoaxonic synapses are the predominant form of synaptic output from these cells (Hughes et al., 2012).…”

Synaptic Organization of VGLUT3 Expressing Low-Threshold Mechanosensitive C Fiber Terminals in the Rodent Spinal Cord

“…For instance, a major group of non-peptidergic nociceptive C fiber that bind the isolectin B 4 terminate in the middle third or inner half of lamina II (lamina IIi), where they form central terminals of Type I glomeruli (Ribeiro-da-Silva and Coimbra, 1982; Gerke and Plenderleith, 2004). Type II glomeruli, a group of glomeruli in lamina IIi-III morphologically distinct from Type I glomeruli, is thought to be formed by terminals originating from myelinated A fibers (Réthelyi et al, 1982; Ribeiro-da-Silva and Coimbra, 1982). By contrast, although C-LTMRs are known to terminate in lamina IIi in the mouse (Seal et al, 2009; Li et al, 2011; Abraira et al, 2017), the terminal morphology and synaptology of this class of primary afferent fiber in the dorsal horn remains unknown.…”