Cortical disinhibition in the neonatal ventral hippocampal lesion model of schizophrenia: New vistas on possible therapeutic approaches

The neonatal ventral hippocampal lesion (NVHL) model of schizophrenia has been extensively used in many laboratories over the past couple of decades. With more than 120 publications from over 15 research groups, this developmental model yields a number of schizophrenia-relevant behavioral, neurochemical and electrophysiological deficits. An important aspect of this model is the delayed emergence of alterations, typically during adolescence despite the manipulation that causes them having been performed during the first postnatal week. Such delayed timing reflects the periadolescent onset of schizophrenia symptoms and may be related to the protracted maturation of cortical circuits, affected in both the disease and the NVHL model. Here, I will review the work we have done regarding the maturation of prefrontal cortical-accumbens circuits during adolescence, and how this maturation is affected in rats with a NVHL. One of the principal elements affected in NVHL rats is the dopamine modulation of prefrontal cortical interneurons, and this finding is convergent with data from many other developmental, genetic and pharmacological models. An altered maturation of interneuron function would yield a disinhibited cortex, and this opens the way to novel therapeutic approaches for treatment and even prevention of schizophrenia.