The Process of Reinnervation in the Dentate Gyrus of Adult Rats: Physiological Events at the Time of the Lesion and during the Early Postlesion Period

Abstract

Destruction of the entorhinal cortex (EC) triggers a number of cellular and molecular responses in the denervated hippocampus and dentate gyrus. The signals that trigger these changes are not known but could include physiological events that occur during the production of the injury or during the early postlesion period. Of particular interest is whether experimental lesions induce seizures and/or spreading depression (SD), both of which have been shown to dramatically alter neuronal and glial gene expression. In the present study, acute neurophysiological techniques were used to evaluate whether seizures or SD occur during the production of EC lesions. Chronic recording techniques were used to monitor electroencephalographic (EEG) activity during the first 24 h after the injury in order to evaluate the extent of postlesion seizures. One or more episodes of SD occurred in 9 of 13 animals during the production of electrolytic EC lesions. However, hippocampal seizures were not observed except for very brief episodes of seizure activity at the onset of an episode of SD. Chronic recordings of postlesion EEG activity revealed that spontaneous electrographic seizures occurred during the first 24 h postlesion in all animals. The spontaneous electrographic seizures were approximately 30 s in duration and were not accompanied by motor convulsions. The first seizures occurred within several hours after the lesion, and seizures continued to occur periodically (at an average frequency of 0.42 per hour) over the 24-h recording period. Seizures occurred on the side of the brain ipsilateral to the lesion in all animals and occurred on the side contralateral to the lesion in 3 of 5 animals. These results indicate that EC lesions produce physiological events that occur variably in different animals; these processes may account for some of the variability in the cellular responses to this “standardized” injury.