A neurodevelopmental model of schizophrenia: neonatal disconnection of the hippocampus.

Abstract

In the context of our current knowledge about schizophrenia, heuristic models of psychiatric disorders may be used to test the plausibility of theories developed on the basis of new emerging biological findings, explore mechanisms of schizophrenia-like phenomena, and develop potential new treatments. In a series of studies, we have shown that neonatal excitotoxic lesions of the rat ventral hippocampus (VH) may serve as a heuristic model. The model appears to mimic a spectrum of neurobiological and behavioral features of schizophrenia, including functional pathology in presumably critical brain regions interconnected with the hippocampal formation and targeted by antipsychotic drugs - the striatum/nucleus accumbens and the prefrontal cortex, and leads in adolescence or early adulthood to the emergence of abnormalities in a number of dopamine related behaviors. Moreover, our data show that even transient inactivation of the ventral hippocampus during a critical period of development, that produces subtle, if any, anatomical changes in the hippocampus, may be sufficient to disrupt normal maturation of the prefrontal cortex (and perhaps, other interconnected late maturing regions) and trigger behavioral changes similar to those observed in animals with the permanent excitotoxic lesion. These results represent a potential new model of aspects of schizophrenia without a gross anatomical lesion.