H. Vanpraag et al., UNILATERAL NEONATAL HIPPOCAMPAL LESION ALTERS SEPTAL INNERVATION AND TROPHISM OF THE ENTORHINAL CORTEX, Experimental neurology, 141(1), 1996, pp. 130-140
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.