Early Withdrawal of Axons from Higher Centers in Response to Peripheral Somatosensory Denervation

Abstract

The mechanisms responsible for long-term, massive reorganization of representational maps in primate somatosensory cortex after deafferentation are poorly understood. Sprouting of cortical axons cannot account for the extent of reorganization, and withdrawal of axons of deafferented brainstem and thalamic neurons, permitting expression of previously silent synapses, has not been directly demonstrated. This study is focused on the second of these. In monkeys, deafferented for two years by section of the cuneate fasciculus at the C1 level, there was extensive withdrawal of axon terminals from thalamus and cortex, detectable a decade before visible atrophy of their parent neuronal somata in the cuneate nucleus or thalamus. Slow, inexorable progression of lemniscal and thalamocortical axonal withdrawal is a neurodegenerative phenomenon likely to be a powerful inducement to compensatory long-term plasticity, a mechanism that can explain the long-term evolution of cortical reorganization and, with it, phantom sensations in spinal patients and amputees.

Large-scale reorganization of the somatosensory cortex following spinal cord injuries is due to brainstem plasticity

“…Furthermore, deafferentation-induced mechanisms operating at different levels can further modify details of the reorganization. The mechanisms can include unmasking and growth of pre-existing connections, changes in neurotransmitter levels and withdrawal of terminals due to deafferentation 20,27,36,[42][43][44] .…”

“…In the brainstem nuclei sprouting of inputs from the trigeminal nucleus into the cuneate nucleus has been shown following dorsal column injuries 22 . Degenerative changes in the cortex, thalamus and cuneate nucleus are observed in monkeys with long-term loss of sensory inputs 20,27 . Thus, mechanisms operating at any one or all of these sites along the somatosensory pathway could potentially contribute to cortical reorganization.…”

AMPA and GABAA/B receptor subunit expression in the cuneate nucleus of adult squirrel monkeys during peripheral nerve regeneration

“…This has substantial influence on receptive field expression at lower levels of the ascending neuroaxis [1,2, 3,5, 34, 35, 38, 39, 40, 54, 56 57, 58]. While corticofugal feedback does play an important role in both immediate unmasking and reorganization within subcortical structures [6, 13, 17, 27, 31, 58], the time-course and extent of changes occurring in the brainstem impose important limitations on cortical reorganization.…”

Rewiring of Afferent Fibers in the Somatosensory Thalamus of Mice Caused by Peripheral Sensory Nerve Transection

“…Axonal changes at supraspinal levels are believed to take months or even years to take place after peripheral nerve injury. For instance, the decrease in axonal branching of afferent fibers to the primate ventral posterolateral thalamic nucleus (VPL) can be seen years after a cuneate fasciculus lesion (Graziano and Jones, 2009), suggesting the retraction of axons and compensatory axonal sprouting from unaffected fibers. In the somatosensory cortex, long-range intracortical axonal sprouting has been reported, but it has also been detected long after amputation (Florence et al, 1998).…”