Cortical sensory map rearrangement after spinal cord injury: fMRI responses linked to Nogo signalling

Abstract

Cortical sensory maps can reorganize in the adult brain in an experience-dependent manner. We monitored somatosensory cortical reorganization after sensory deafferentation using functional magnetic resonance imaging (fMRI) in rats subjected to complete transection of the mid-thoracic spinal cord. Cortical representation in response to spared forelimb stimulation was observed to enlarge and invade adjacent sensory-deprived hind limb territory in the primary somatosensory cortex as early as 3 days after injury. Functional MRI also demonstrated long-term cortical plasticity accompanied by increased thalamic activation. To support the notion that alterations of cortical neuronal circuitry after spinal cord injury may underlie the fMRI changes, we quantified transcriptional activities of several genes related to cortical plasticity including the Nogo receptor (NgR), its co-receptor LINGO-1 and brain derived neurotrophic factor (BDNF), using in situ hybridization. We demonstrate that NgR and LINGO-1 are down-regulated specifically in cortical areas deprived of sensory input and in adjacent cortex from 1 day after injury, while BDNF is up-regulated. Our results demonstrate that cortical neurons react to sensory deprivation by decreasing transcriptional activities of genes encoding the Nogo receptor components in the sensory deprived and the anatomically adjacent non-deprived area. Combined with the BDNF up-regulation, these changes presumably allow structural changes in the neuropil. Our observations therefore suggest an involvement of Nogo signalling in cortical activity-dependent plasticity in the somatosensory system. In spinal cord injury, cortical reorganization as shown here can become a disadvantage, much like the situation in amblyopia or phantom sensation. Successful strategies to repair sensory pathways at the spinal cord level may not lead to proper reestablishment of cortical connections, once deprived hind limb cortical areas have been reallocated to forelimb use. In such situations, methods to control cortical plasticity, possibly by targeting Nogo signalling, may become helpful.