P0312 - Animal models: Possible avenue to understanding schizophrenia

Abstract

Schizophrenia is one of the most devastating neuropsychiatric disorders. One of the most consistent findings in schizophrenia is a decrease in cell number and volume of the medial dorsal nucleus (MD) of the thalamus which has reciprocal connections to the prefrontal cortex, another region affected in schizophrenia. During development, the MD aides in the differentiation and maturation of pyramidal cells in the prefrontal cortex. To better understand the role of the MD in schizophrenia we lesioned the MD of postnatal day 4 rats and examined their prefrontal cortex as adults. In rats, the MD projects to dorsolateral anterior (human area 9), medial prelimbic (human area 32) and Cg-1 (human area 24). We hypothesized that a lesion of the MD would lead to morphological changes in all three regions similar to that observed in humans. Using a Golgi stain we counted the number of primary and secondary dendrites and determined spine density in the three regions. Analysis of layers III and V pyramidal cells showed a significant reduction in primary dendrites III/V (Cg-1 25%/23%, prelimbic 25%/25% and dorsolateral 24%/15%) and secondary dendrites (Cg-1 40%/34%, prelimbic 40%/32% and dorsolateral 41%/30%). Using two different counting methods we observed that spines on primary and secondary dendrites were significantly reduced for both laminas for all three regions. These current data suggest that a lesion of the MD early in development affects dendritic morphology in the prefrontal cortex similar to that observed in schizophrenia making this model a good candidate for better understanding of schizophrenia.