Temporally extended retrograde amnesia for spatial information resulting from afterdischarges induced by electrical stimulation of the dorsal hippocampus in mice

Abstract

The present study was conducted in order to examine whether reversible disruption of hippocampal activity using repeated (four times), spaced (at hourly intervals) electrical stimulation (at current levels producing afterdischarges [ADs]) of the dorsal hippocampus would produce a temporally graded retrograde amnesia for two-choice spatial discrimination problems acquired at different time intervals before treatment. Mice were trained successively on five different two-choice discrimination problems in one of two distinct elevated 8-arm radial mazes (A and B). The first two problems were acquired in Maze A, and the final three problems in Maze B. Hippocampal ADs were elicited approximately 24 h after the mice had acquired the last discrimination problem (B3). One week later, subjects were tested for retention of all five discrimination problems. Results indicated that, as compared with control groups, experimental subjects were severely impaired for retention of the three discrimination problems acquired from 10 days to 5.5 weeks earlier in Maze B, but showed no deficit for the problems acquired 7 weeks earlier in Maze A. However, for problems acquired in Maze B, no temporal gradient for amnesia was observed, although control mice exhibited significant forgetting with increasing retention intervals. Temporally extended but ungraded retrograde disrupting effect of hippocampal stimulation for discriminations acquired in Maze B is discussed.