ABSTRACT
Low-frequency stimulation applied through indwelling electrodes has been used to depress or depotentiate synaptic efficacy. Moreover it has been reported to inhibit seizure expression and progression when started either during or after seizures. We have recently shown that low-frequency stimulation can also reduce the size of seizure-enlarged movement representations (motor maps) when delivered after 30 afterdischarges that had propagated from the hippocampus to the neocortex. This study was designed to examine the effects of low-frequency stimulation delivered to the corpus callosum on motor map topography when applied during or after each elicited seizure. Specifically, 15 min of 1 Hz stimulation was applied to the corpus callosum either concurrent with or immediately following a neocortical afterdischarge that had propagated from the hippocampus. Long-Evans hooded rats were electrically stimulated twice daily in the right ventral hippocampus until the first neocortical afterdischarge was elicited. Rats then received low-frequency stimulation which began either with the afterdischarge or following each afterdischarge for 20 additional kindling sessions; a sham low-frequency stimulation group was also included. Afterdischarges were recorded from both hippocampal and neocortical sites, and seizure expression was documented. One to six days following the last stimulation session, forelimb movement representations were derived using high-resolution intracortical microstimulation in the left sensorimotor neocortex. Low-frequency stimulation following each kindled seizure, suppressed behavioral seizure severity and hippocampal afterdischarge duration, as well as attenuated kindling-induced motor map expansion.
Subject(s)
Corpus Callosum , Electric Stimulation Therapy/methods , Motor Cortex/physiopathology , Movement , Neural Inhibition , Seizures/prevention & control , Analysis of Variance , Animals , Brain Mapping , Disease Models, Animal , Hippocampus/physiology , Hippocampus/physiopathology , Kindling, Neurologic , Neocortex/physiopathology , Neural Pathways/physiopathology , Rats , Rats, Long-Evans , Seizures/physiopathologyABSTRACT
Repeated application of low-frequency stimulation can interrupt the development and progression of seizures. Low-frequency stimulation applied to the corpus callosum can also induce long-term depression in the neocortex of awake freely moving rats as well as reduce the size of neocortical movement representations (motor maps). We have previously shown that seizures induced through electrical stimulation of the corpus callosum, amygdala or hippocampus can expand the topographical expression of neocortical motor maps. The purpose of the present study was to determine if low-frequency stimulation administered to the corpus callosum could reverse the expansion of neocortical motor maps induced by seizures propagating from the hippocampus. Adult Long-Evans hooded rats were electrically stimulated in the right ventral hippocampus, twice daily until 30 neocortical seizures were recorded. Subsequently, low-frequency stimulation was administered to the corpus callosum once daily for 20 sessions. High-resolution intracortical microstimulation was then utilized to derive forelimb-movement representations in the left (un-implanted) sensorimotor neocortex. Our results show that hippocampal seizures result in expanded motor maps and that subsequent low-frequency application can reduce the size of the expanded motor maps. Low-frequency stimulation may be an effective treatment for reversing seizure-induced reorganization of brain function.
