Neonatal ventral hippocampal lesions produce an elevation of DeltaFosB-like protein(s) in the rodent neocortex.

Rats that have sustained bilateral excitotoxic lesions of the ventral hippocampus (VH) as neonates develop behavioral abnormalities as adults (hyper-responsiveness to stress, diminished prepulse inhibition, and increased sensitivity to dopamine agonists), which resemble certain aspects of schizophrenia. Although this behavioral profile is thought to reflect dysregulation of the mesolimbic dopamine system, the precise neuroanatomical and neurochemical substrates that mediate the emergence of these abnormalities during brain maturation are unclear. In order to identify putative sites responsible for the development of behavioral abnormalities following neonatal lesions of the VH, we utilized the chronic neuronal activity marker DeltaFosB. By comparison to sham lesioned animals, bilateral destruction of the VH elevated DeltaFosB expression throughout the caudate putamen and neocortex of animals lesioned as neonates. These increases were not observed in rats lesioned as young-adults, suggesting that DeltaFosB induction in the cortex of neonatally lesioned rats may be related to altered cortical neurodevelopment. Accumulating evidence implicates DeltaFosB in mediation of the long-lasting effects of altered dopaminergic neurotransmission on behavior. The present findings are consistent with this proposal and suggest that elevated expression of DeltaFosB identifies overactive neurons that may contribute to the enhanced sensitivity to stress and dopaminergic agonists of rats that have sustained bilateral ventral hippocampal lesions as neonates.