Changes in the firing properties of neurons in the dentate gyrus with denervation and reinnervation: Implications for behavioral recovery

Abstract

The present study evaluates how the activity of neurons in the dentate gyrus of adult rats is affected by removal of the projection from the ipsilateral entorhinal cortex (EC) and by the reinnervation which follows this injury. We evaluated the average firing rate and characterized interstimulus interval (ISI) parameters for single units in the granule cell layer of the dentate gyrus in two ways: (I) by recording the activity of single neurons prior to and at 15 min and 2, 4, 6, and 8 h. following a unilateral EC lesion; and (II) by calculating average rates for samples of neurons at 2, 4, 6, 8, and 14 days postlesion. Of a sample of 31 neurons whose activity was recorded before and after an EC lesion, 27 (87%) showed decreased activity, and 4 (13%) showed increased activity. The average prelesion firing rate for all cells was 6.5 spikes/s, and the average rate decreased to 2.5 spikes/s at 15 min postlesion. The average firing rate remained depressed for the 8-h recording session, although it was not possible to maintain the recordings for all cells. Evaluations of ISI histograms revealed three general types: (a) a skewed distribution with a single peak; (b) a bimodal distribution with an early peak at intervals of a few ms and a later peak at approximately the same interval as the distributions with single peaks; (c) cells with low firing rates and more or less rectangular distributions. Cells producing each type of ISI histogram exhibited decreases in firing after EC lesions. However, the 4 neurons that exhibited increases in firing had relatively low firing rates prior to the lesion. There were no significant changes in the coefficient of variation or skewness of the ISI histograms following the lesions. The statistical dependency of successive ISIs as revealed by serial correlograms was relatively low in the prelesion sample, and showed no consistent change following the lesion. Comparison of the average firing rates of different samples of neurons at 2–14 days postlesion revealed that the average activity of neurons in the granule cell layer remained depressed at 2 and 4 days postlesion. However, the activity recovered to a level comparable to the prelesion control by 8 days postlesion. The time course of recovery of unit activity was comparable to the time course of sprouting as revealed by previous electrophysiological studies. Since sprouting of the dentate gyrus has previously been shown to be correlated with recovery of function, we discuss how the recovery of unit activity might play a role in the behavioral recovery.