Formation of somatosensory detour circuits mediates functional recovery following dorsal column injury

Abstract

Anatomically incomplete spinal cord injuries can be followed by functional recovery mediated, in part, by the formation of intraspinal detour circuits. Here, we show that adult mice recover tactile and proprioceptive function following a unilateral dorsal column lesion. We therefore investigated the basis of this recovery and focused on the plasticity of the dorsal column-medial lemniscus pathway. We show that ascending dorsal root ganglion (DRG) axons branch in the spinal grey matter and substantially increase the number of these collaterals following injury. These sensory fibers exhibit synapsin-positive varicosities, indicating their integration into spinal networks. Using a monosynaptic circuit tracing with rabies viruses injected into the cuneate nucleus, we show the presence of spinal cord neurons that provide a detour pathway to the original target area of DRG axons. Notably the number of contacts between DRG collaterals and those spinal neurons increases by more than 300% after injury. We then characterized these interneurons and showed that the lesion triggers a remodeling of the connectivity pattern. Finally, using re-lesion experiments after initial remodeling of connections, we show that these detour circuits are responsible for the recovery of tactile and proprioceptive function. Taken together our study reveals that detour circuits represent a common blueprint for axonal rewiring after injury.

The tracts, cytoarchitecture, and neurochemistry of the spinal cord

“…The unmyelinated population is thought to directly mediate transmission from nociceptors; injection of capsaicin in rats showed a decrease in the number of unmyelinated fibers in both gracile and cuneate fasciculi (Patterson et al, 1992). These fasciculi are responsible for transmitting information regarding discriminatory touch (Kitai & Weinberg, 1968), deep pressure (Loutit & Potas, 2020), proprioception (Granier et al, 2020), and vibration (Shintani et al, 2000). Indeed, lesions to the dorsal column have led to deficits in some or all of the above functions.…”

How Does the Central Nervous System for Posture and Locomotion Cope With Damage-Induced Neural Asymmetry?

“…Dorsal hemisection, which suppress half of sensory inputs ascending to brain centers, has dramatic acute effects on locomotion, affecting notably paw placing during skilled walking, until sensory afferent reorganization within the ipsilesional hemicord occurs and allows functional recovery. In mice with such lesions, ascending dorsal root neurons increased branching below the lesion site and, in particular, connected propriospinal INs projecting into the cuneate nucleus, constituting so a detour circuit to brainstem centers (Granier et al, 2020), and beyond, to the primary sensory-motor cortex (as afore suggested in rats and monkeys; Kaas et al, 2008). Functional restoration of bilateral tactile and proprioceptive sensation occurred in these animals within weeks, demonstrating the exceptional ability of sensory systems to compensate for selective alterations of their central pathways.…”

Plasticity of the Injured Spinal Cord

“…Mainly in these studies, in order to study the somatosensory tract plasticity, the authors performed dorsal column injury. In this model, lemniscal tracts show an impressive ability to sprout and regrow and more importantly, to form functional synapses [17,18].…”