Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: recovery of alternation performance following unilateral entorhinal cortex lesions.

Following unilateral lesions of the entorhinal cortex (E.C.) of the rat, cells in the dentate gyrus which have been deprived of their normal ipsilateral input are reinnervated in part by axons from the contralateral E.C. The proliferation of this crossed projection occurs largely between 8 and 12 days postlesion. The present experiments analyze changes in alternation behavior which occur during this period of afferent proliferation. Rats were trained to alternate responses (L-R) in a T-maze for food reward. Bilateral E.C. lesions resulted in a persistent deficit in alternation performance which did not recover after over 50 days of postoperative testing. Unilateral E.C. lesions, however, resulted in a transient deficit in alternation which recovered over time to preoperative levels. For example, animals permitted a 10-day recovery before the initiation of postlesion testing exhibited no more of a performance deficit than following a 10-day no-training period alone. However, animals permitted only a 3-day postoperative recovery were impaired in the alternation task until 10-12 days postlesion, despite daily training. Thus, recovery of performance following unilateral lesions was dependent on postlesion time rather than the amount of testing/retraining. Since bilateral lesions resulted in a persistent performance deficit while unilateral lesions resulted in a deficit with recovery, we hypothesize that behavioral recovery might be related to the reinnervation of the dentate gyrus by the contralateral E.C. To test this hypothesis, secondary lesions were placed in operated-recovered animals. Secondary lesions of the surviving E.C. resulted in a deficit in alternation performance similar to that following one stage bilateral lesions. In addition, secondary lesions of the dorsal psalterium (the fiber tract which carries the corssed E.C.-dentate projections) also disrupted performance in operated-recovered animals. Primary lesions of the dorsal psalterium alone had only slight and transient effects on alternation performance, however. Thus, the time course of the recovery, the results following bilateral lesions, and the results of secondary lesions are all consistent with the hypothesis that recovery of alternation performance following unilateral E.C. lesions may depend upon the reinnervation of the dentate gyrus by the contralateral E.C.