Multiple synapse formation in the motor cortex opposite unilateral sensorimotor cortex lesions in adult rats.

Unilateral damage to the forelimb region of the sensorimotor cortex (FLsmc) in adult rats has previously been found to result in dendritic growth and synaptogenesis in layer V of the contralateral motor cortex. The neuronal growth appears to be mediated in part by lesion-induced changes in the use of the forelimbs. Whether these neuronal changes involve alterations in the structure and/or configuration of synaptic connections in layer V has not previously been investigated. The present study used stereological measures to characterize structural alterations in axonal processes and synaptic connections using electron micrographs generated in a previous study of the motor cortex contralateral to FLsmc lesions. Of primary interest were synapses formed by multiple synaptic boutons (MSBs), which have recently been found to be a major component of experience-related neocortical plasticity, and synapses with perforated postsynaptic densities (PSDs), which are putatively associated with enhanced synaptic efficacy. In comparison with sham-operated rats, there was an increase in the proportion and ratio of synapses to neurons formed by MSBs and in synapses with perforated PSDs at 30 days after the lesions. Furthermore, perforated synapses formed by MSBs were markedly increased at 18 and 30 days after the lesion in comparison with sham-operated rats. Preceding these synaptic structural changes (at 10 days postlesion), myelinated axons were reduced in volume fraction and volume per neuron in comparison with sham-operated rats but returned to normal levels at subsequent time points. These results are consistent with a lesion-induced degeneration and subsequent sprouting of axons. Together, these data indicate that a major restructuring of synaptic connectivity occurs in the cortex opposite FLsmc lesions in adult animals. This lesion-induced restructuring may be guided by ongoing changes in the use of the forelimbs.