UNILATERAL NEONATAL HIPPOCAMPAL LESION ALTERS SEPTAL INNERVATION AND TROPHISM OF THE ENTORHINAL CORTEX

It is generally assumed that central nervous system injury sustained d uring development produces less severe behavioral deficits than damage in the adult, due to increased plasticity of the immature brain. Howe ver; developmental plasticity may also exacerbate deficits, presumably through formation of anomalous connections. Previous studies showed t hat after unilateral neonatal, but not adult, electrolytic hippocampal lesion spatial memory is severely impaired. To determine whether the memory deficit is correlated with anatomical changes in a major hippoc ampal afferent system, the septal input, the anterograde tracer Phaese olus vulgaris leucoagglutinin was injected into the medial septum 2 mo nths after unilateral neonatal hippocampal lesion. The density of sept al fiber projections into the entorhinal cortex (EC) was found to be i ncreased. Choline-acetyltransferase activity increased significantly i n the EC 2 months postlesion, suggesting that septal cholinergic fiber s are sprouting. Finally, nerve growth factor (NGF), which can mediate sprouting, was measured in the EC. NGF protein increased transiently 7 to 12 days postlesion in the ipsilateral EC, suggesting that increas ed trophic support is associated with growth of septal afferents into the EC. Thus, neonatal hippocampal lesion causes a reorganization of a xonal connections associated with elevated NGF in the target region of the increased septal input. Moreover, since previous studies showed t hat the neonatal lesion is accompanied by a spatial memory deficit, th is plasticity may compromise function of the remaining circuitry. (C) 1996 Academic Press, Inc.