Does Reorganization in the Cuneate Nucleus Following Neonatal Forelimb Amputation Influence Development of Anomalous Circuits Within the Somatosensory Cortex?

Abstract

Neonatal forelimb amputation in rats produces sprouting of sciatic nerve afferent fibers into the cuneate nucleus (CN) and results in 40% of individual CN neurons expressing both forelimb-stump and hindlimb receptive fields. The forelimb-stump region of primary somatosensory cortex (S-I) of these rats contains neurons in layer IV that express both stump and hindlimb receptive fields. However, the source of the aberrant input is the S-I hindlimb region conveyed to the S-I forelimb-stump region via intracortical projections. Although the reorganization in S-I reflects changes in cortical circuitry, it is possible that these in turn are dependent on the CN reorganization. The present study was designed to directly test whether the sprouting of sciatic afferents into the CN is required for expression of the hindlimb inputs in the S-I forelimb-stump field. To inhibit sprouting, neurotrophin-3 (NT-3) was applied to the cut nerves following amputation. At P60 or older, NT-3-treated rats showed minimal sciatic nerve fibers in the CN. Multiunit electrophysiological recordings in the CN of NT-3-treated, amputated rats revealed 6.3% of sites were both stump/hindlimb responsive, compared with 30.5% in saline-treated amputated animals. Evaluation of the S-I following GABA receptor blockade, revealed that the percentage of hindlimb responsive sites in the stump representation of the NT-3-treated rats (34.2%) was not significantly different from that in saline-treated rats (31.5%). These results indicate that brain stem reorganization in the form of sprouting of sciatic afferents into the CN is not necessary for development of anomalous hindlimb receptive fields within the S-I forelimb/stump region.

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

“…More importantly, receptive field changes at the level of the brainstem are essential for the expression of reorganization at the level of the cortex [32]. Thus, the pattern and extent of cortical reorganization is highly correlated with representational changes evident at subcortical levels [17].…”

“…In this way the engram [see, 19]. of the reorganized circuit could be masked by corticofugal feedback [18, 32, 33 50, 58], while being maintained within the network.…”

Interhemispheric neuroplasticity following limb deafferentation detected by resting-state functional connectivity magnetic resonance imaging (fcMRI) and functional magnetic resonance imaging (fMRI)

“…Deafferentation can cause detectable changes in the sensory cortex, which was first demonstrated in a rat by whisker removal (Van der Loos and Woolsey 1973). Reorganization is not limited to the cortex and can involve the thalamus (Kaas 1999; Nicolelis et al 1993) and other subcortical structures (Lane et al 2008). Neuroplasticity in the CNS occurs in a time-dependent manner (Cusick 1996) and can include many processes such as the sprouting of new connections or the immediate loss of inhibitory inputs from one region to another (Navarro et al 2007).…”

Forelimb amputation-induced reorganization in the cuneate nucleus (CN) is not reflected in large-scale reorganization in rat forepaw barrel subfield cortex (FBS)

“…The resulting reorganization has been reported using electrophysiological mapping of receptive fields (Rhoades et al, 1993), transganglionic labeling (Maslany et al, 1990; Maslany et al, 1991), receptor expression mapping (Foschini et al, 1994), and metabolic uptake measurement (Crockett et al, 1993). There is also evidence that CN reorganization plays some role in cortical reorganization (Bowlus et al, 2003; Killackey and Dawson, 1989; Lane et al, 1995; Lane et al, 2008). …”