Abstract
Sensorimotor restriction by a 14-day period of hindlimb unloading (HU) in the adult rat induces a reorganization of topographic maps and receptive fields. However, the underlying mechanisms are still unclear. Interest was turned towards a possible implication of intracellular MAPK signaling pathway since Extracellular-signal-Regulated Kinase 1/2 (ERK1/2) is known to play a significant role in the control of synaptic plasticity. In order to better understand the mechanisms underlying cortical plasticity in adult rats submitted to a sensorimotor restriction, we analyzed the time-course of ERK1/2 activation by immunoblot and of cortical reorganization by electrophysiological recordings, on rats submitted to hindlimb unloading over four weeks. Immunohistochemistry analysis provided evidence that ERK1/2 phosphorylation was increased in layer III neurons of the somatosensory cortex. This increase was transient, and parallel to the changes in hindpaw cortical map area (layer IV). By contrast, receptive fields were progressively enlarged from 7 to 28 days of hindlimb unloading. To determine whether ERK1/2 was involved in cortical remapping, we administered a specific ERK1/2 inhibitor (PD-98059) through osmotic mini-pump in rats hindlimb unloaded for 14 days. Results demonstrate that focal inhibition of ERK1/2 pathway prevents cortical reorganization, but had no effect on receptive fields. These results suggest that ERK1/2 plays a role in the induction of cortical plasticity during hindlimb unloading.
Highlights
Cortical maps are highly dynamic structures which can reorganize in response to changes in environmental demands or in sensorimotor experience
We showed a progressive enlargement of the receptive fields (RF) across the different periods of hindlimb unloading (HU) (HU7: +4%, ns; HU14: +19%, p,0.05; HU28: +52%, p,0.001)
The main objective of the present study was to determine whether extracellular-signal-regulated kinase 1/2 (ERK1/2) signaling pathway was involved in the reorganization of cortical maps in HU rats
Summary
Cortical maps are highly dynamic structures which can reorganize in response to changes in environmental demands or in sensorimotor experience. Amputation, peripheral nerve lesion or restriction in sensory experience induce remodeling of the topological cortical maps [1]. Such a remodeling is described in the somatosensory cortex of adult rats submitted to hindlimb unloading (HU) [2,3], a situation commonly used in rats to mimic the effects of confinement to bed in patients, or even space-flight. Our first objective was to establish a time-course of cortical reorganization of adult rats submitted to 7 to 28 days of HU. PD98059 is a highly selective inhibitor of MAP kinase kinase activation, resulting in decreased phosphorylation of ERK1 and ERK2 [15], Our main conclusion is that molecular mechanisms of cortical map plasticity involve ERK1/2 activation
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