Accelerating hippocampal sprouting by making unilateral progressive lesions of the entorhinal cortex spared the spatial memory of rats tested for retention of a learned alternation task. Subsequent transection of the sprouted crossed temporodentate pathway (CTD), as well as a simultaneous CTD transection and progressive entorhinal lesion, produced a persistent deficit on the memory task. These results suggest that CTD sprouting, which is homologous to the original perforant path input to the dentate gyrus of the hippocampus, is behaviorally significant and can ameliorate at least some of the memory deficits associated with hippocampal deafferentation.To account for recovery of function observed after human brain trauma, clinicians often invoke concepts such as functional reorganization or functional substitution (1-3). Although the notion that the central nervous system (CNS) may undergo reorganization to compensate for the loss of some behavioral capacity is appealing, the experimental support for such a notion is scant. Numerous investigations over the last two decades, however, have established that neurons surviving an insult to the CNS may undergo extensive terminal proliferation and form functional contacts with cells deprived of their original inputs (4, 5). Given the ubiquitous nature of this ''sprouting'' response, the possibility exists that the formation of new contacts after brain injury may be a neural substrate mediating functional reorganization. The wealth of studies documenting the neuroplasticity of the CNS notwithstanding, the behavioral significance of these new connections remains as yet unclear.Lesion-induced sprouting by the crossed temporodentate pathway (CTD) in rats has been implicated in the recovery of spatial memory after deafferentation of the hippocampus, a structure which appears to be crucial for learning and memory (6-10). Following a unilateral lesion of the entorhinal cortex (EC), at least three hippocampal inputs expand their synaptic fields to reinnervate the denervated dentate gyrus (DG) of the hippocampus (4, 5). These are the crossed entorhinal projection (i.e., the CTD), the acetylcholinesterase-containing septodentate pathway, and the commissural͞associational (C͞A) inputs. The CTD, which projects to the rostral dentate via the dorsal psalterium (DP), is particularly interesting. It originates in the contralateral homologue of the damaged area and, upon sprouting 6 to 10 days postlesion, shares many of the physiological characteristics of the original input, the perforant path. The proliferated CTD input: (i) is capable of discharging the granule cells, the targets of the perforant path (11); (ii) exhibits habituation-like decrements in transmission reminiscent of the normal ipsilateral input (12); and (iii) potentiates population excitatory postsynaptic potentials of the granule cells as does the perforant path (13).If sprouting by the crossed entorhinal pathway contributes to recovery of function, procedures that accelerate this sprouting should concomitantly ...

The entorhinal cortex participates in a variety of spatial and locomotor behaviors that are thought to be mediated by the hippocampal formation. The present study examined the possibility that the entorhinal area contributes to the maintenance of an operant behavior in which the hippocampus is also implicated-differential reinforcement of low-rate responding (DRL). Rats with bilateral entorhinal cortex lesions or sham operations were tested for retention of a preoperatively learned DRL (lO-sec delay) task. Rats with entorhinallesions were impaired on measures of response rate, temporal discrimination, and response efficiency for 2 to 3 weeks after surgery. Histological analyses indicated that all the rats sustained complete entorhinallesions. The entorhinal cortex may be an important component of the hippocampal formation contributing to the performance of DRL tasks.