Neonatal lesions of the entorhinal cortex induce long-term changes of limbic brain regions and maze learning deficits in adult rats

We here investigated the effects of neonatal lesions of the entorhinal cortex (EC) in rats on maze learning and on structural alterations of its main projection region, the hippocampus, as well as other regions with anatomical connections to the EC that are involved in maze learning. Since early brain damage is considered to be involved in certain neuropsychiatric diseases, this approach sought to model certain aspects of this etiopathogenesis. Bilateral neonatal lesions were induced on postnatal day 7 by microinjection of ibotenic acid (1.3 mu g/0.2 mu I phosphate-buffered saline (PBS)) into the EC. Naive and sham-lesioned rats served as controls. Rats were trained and tested on an eight-arm radial maze for allocentric and egocentric learning. Subsequently, gold-chloride staining and immunohistochemical staining for the microtubule-associated protein MAP-2 was used to assess myelination and dendritic density in the hippocampus, striatum and medial prefrontal cortex (mPFC) of these rats. Additionally, parvalbumin-expressing, presumably GABAergic interneurons, were evaluated in these regions. Performance in both the allocentric and the egocentric strategy was disturbed after neonatal EC lesion as shown by an increase of repeated arm entries, which indicates disturbed working memory. Histological evaluation revealed that the density of parvalbumin-immunopositive neurons and myelin sheaths was reduced in the hippocampus but not in the striatum and mPFC in neonatally lesioned rats. Density of MAP-2 staining did not differ between groups in all regions tested. Since structural alterations were only found in the EC and hippocampus our findings support their eminent role in working memory and show that no functional restoration occurs after neonatal lesions. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.