The effect of prolonged cortical spreading depression on learning and memory in rats

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Abstract
Memory impairment evoked by prolonged cortical spreading depression (PCSD) was examined in 387 rats. PCSD was maintained for 5 hrs by repeated applications of 25% KCl to the exposed cortical surface. Behavioral tests were performed 24 or more hours after PCSD. Whereas a single application of 25% KCl does not affect subsequent learning, acquisition of a simple T‐maze avoidance reaction is slower and exploration of a novel environment is impaired during 3–5 days following PCSD. The effect of CSD on the memory depends on the total duration of the depression. While a single KCl application has a negligible amnesic effect, PCSD prevents later retrieval of moderately overlearned (to‐criterion learning on 3 consecutive days) T‐maze habit but does not affect markedly overlearned behavior (to‐criterion learning on 12 consecutive days). Similarly PCSD impairs the exploration of a novel but not of a familiar environment. Even moderately overlearned habits remain unaffected by PCSD applied 7–12 days after completion of learning. The amnesic effects of PCSD are not permanent, retrieval of the impaired experience improves over 7–14 days to control level. Since spontaneous EEG and evoked responses are more or less normal 24 hr after PCSD, it is proposed that PCSD interferes with the metabolic phase of engram formation. The relative significance of the components of the PCSD effect affecting learning and memory is discussed.