Neuroanatomical changes in the adult rat brain after neonatal lesion of the medial prefrontal cortex.

After neonatal lesions of the medial prefrontal cortex (mPFC) the lesion cavity are considerably replaced by neuronal tissue ("filled-in-tissue"). This is accompanied by sparing of some behavioral functions related to the mPFC, while others are deteriorated. We here investigated the neuroanatomical integration of the filled-in-tissue. Bilateral neonatal (postnatal day 7) excitotoxic lesions were induced by microinjection of ibotenate into the mPFC. Immunohistochemical staining for the neuronal marker NeuN and the glia cell marker GFAP in adult rats confirmed that the filled-in-tissue consists of neuronal tissue with disturbed lamination but without reactive gliosis. The afferents to the mPFC were marginally altered as shown by almost normal distribution of retrogradely labeled cells in regions projecting to the mPFC after injection of the retrograde tract tracer fluorogold into the filled-in-tissue. Although virtually no transport was found after injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the filled-in-tissue, injections of fluorogold into the nucleus accumbens and mediodorsal thalamus revealed that neurons of the filled-in-tissue project at least to the nucleus accumbens. Additionally, after neonatal mPFC lesions the density of parvalbumin-immunoreactive, presumably GABAergic interneurons, was increased in the amygdala and hippocampus and myelin sheaths were reduced in several cortical and subcortical regions as shown by goldchloride staining. Together, these findings indicate restored anatomical connectivities of the filled-in-tissue that might be responsible for the sparing of behavioral function in some mPFC related tasks, but may also explain disturbed function as a consequence of faulty information transfer between subcortical regions and the filled-in-tissue of the mPFC.