Elsevier

Neuroscience

Volume 133, Issue 2, 2005, Pages 463-470
Neuroscience

Clinical neuroscience
Alterations in dendritic morphology of prefrontal cortical and nucleus accumbens neurons in post-pubertal rats after neonatal excitotoxic lesions of the ventral hippocampus

https://doi.org/10.1016/j.neuroscience.2005.02.021Get rights and content

Abstract

Neonatal ventral hippocampal (nVH) lesions in rats result in adult onset of a number of behavioral and cognitive abnormalities analogous to those seen in schizophrenia, including hyperresponsiveness to stress and psychostimulants and deficits in working memory, sensorimotor gating and social interaction. Molecular and neurochemical alterations in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of nVH-lesioned animals suggest developmental reorganization of these structures following neonatal lesions. To determine whether nVH lesions lead to neuronal morphological changes, we investigated the effect of nVH lesion on dendritic structure and spine density of pyramidal neurons of the PFC and medium spiny neurons of the NAcc. Bilateral ibotenic acid-induced lesion of the VH was made in Sprague-Dawley pups at postnatal day 7 (P7); and at P70, neuronal morphology was quantified by modified Golgi-Cox staining. The results show that length of basilar dendrites and branching and the density of dendritic spines on layer 3 pyramidal neurons were significantly decreased in rats with nVH lesions. Medium spiny neurons from the NAcc showed a decrease in the density of dendritic spines without significant changes in dendritic length or arborization. The data, comparable to those observed in the PFC of schizophrenic patients, suggest that developmental loss of excitatory projections from the VH may lead to altered neuronal plasticity in the PFC and the NAcc that may contribute to the behavioral changes in these animals.

Section snippets

Neonatal lesions

Pregnant Sprague-Dawley rats were obtained at gestational days 14–17 from our animal facility (University of Puebla, Puebla, Mexico). Animals were individually housed in a temperature- and humidity-controlled environment on a 12-h light/dark cycle with free access to food and water. All animal procedures were in strict accordance with the guidelines of the Mexican Council for Animal Care and the Canadian Council for Animal Care and were approved by the Universidad Autónoma de Puebla Animal Care

Verification of the lesion

Animals with neonatal ibotenic acid injections showed bilateral neural loss and atrophy of the ventral hippocampal formation, as reported previously (Flores et al 1996, Brake et al 1999). A schematic representation of the extent of the lesion is shown in Fig. 1. Cavities resulting from the lesion were also frequently seen. In all lesioned animals used in the study, the dorsal-anterior portion of the hippocampal formation was spared.

Locomotor activity

The effect of nVH lesion on spontaneous locomotor activity of

Discussion

The major finding of this study is that the basilar dendrites of the prefrontal cortical pyramidal neurons from post-pubertal nVH-lesioned animals show morphological changes in the form of reduced length and arborization as well as decreased density of the dendritic spines. In addition, medium spiny neurons of the NAcc in the same animals show reductions in dendritic spine density but without significant alterations in dendritic length and branching. These changes are associated with increased

Acknowledgments

This work was supported by CONACYT No. 60446-M and VIEP-BUAP No. i.v. 34–04/SAL/G, Mexico and CIHR, Canada. We are grateful to Dr. Carlos Escamilla for his help in animal care. A.B.S. and G.A. are recipients of studentships from Puebla University. G.F. is a member of the Researcher National System of Mexico. L.K.S. is Chercheur National of the FRSQ.

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