Impairment of functional inhibition in the contralateral cortex following perinatally acquired malformations in rats

Abstract

Neonatal freeze lesions in newborn rats induce focal malformations of the cerebral cortex mimicking human polymicrogyria which is a common cause of epilepsy and neuropsychological deficits in children and adults. Experimental and clinical studies demonstrated hyperexcitability in the malformation itself and peridysplastic cortex associated with a widespread imbalance of excitatory and inhibitory function and extensive alterations in cortical connectivity. We investigated the integrity of functional cortical inhibition using a paired pulse paradigm in brain slice preparations of adult freeze-lesioned rats. In contrast to previous electrophysiological studies focusing on the dysplastic cortex and the ipsilateral hemisphere, we here mapped both hemispheres. Extracellular field potentials were evoked by application of double pulses at the border of layer VI/white matter and recorded in layer II/III. Evaluation of the ratio of the field potential amplitudes at different recording positions allowed an assessment of regional functional inhibition. Using this approach, we observed a significant reduction of functional inhibition in the somatosensory cortex of the contralateral hemisphere, whereas only slight alterations were detected in the ipsilateral lesion surround. Our results provide evidence that focal cortical malformations not only impair cortical excitability in the ipsilateral hemisphere but also induce a disinhibition of the contralateral cortex.