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The major goal of Dr. Srivastava鈥檚 laboratory is to understand the role of neurodevelopmental and intracellular signalling mechanisms in the pathophysiology of schizophrenia using a variety of hypothesis-driven animal models. Some currently active projects are: 1. Neonatal Ventral Hippocampus (NVH) Lesion Model (funded by CIHR and NIMH). Structural hippocampal abnormalities are often described in schizophrenia. We experimentally induce lesions in the hippocampus in rat pups. Our studies show that, at post-pubertal ages, NVH-lesioned show abnormalities in a number of cognitive, motor, and social behaviours that have face validity with human schizophrenia. Our recent studies reveal abnormal synaptic plasticity (LTD) of the prefrontal cortex and cognition in the NVH-lesioned animals that is mediated by dysfunctional alpha-1 adrenergic receptor signaling (Protein kinase C and ERKs). Current research efforts are aimed at further understanding the mechanisms and importance of these changes to schizophrenia. 2. Mice with deletion in Dysbindin-1 gene (Sandy mice) (funded by CIHR). Dysbindin-1 is reported to be a susceptibility gene for schizophrenia and regulated glutamate transmission. Using mice with a natural mutation in the dysbindin-1 gene, we are assessing the role of dysbindin in glutamate-related behaviours and metabotropic glutamate receptor signalling. 3. Rats with prenatal (i.e., maternal) infection (funded by a CIHR Team grant). Maternal infections are reported to be an important environmental risk factor for schizophrenia. This project aims to determine brain changes in rats born to mothers treated with mimics of bacterial and viral infections (e.g., LPS and poly IC) using a multidisciplinary approach including behaviour, neuronal, morphological, and molecular analyses. 4. Psychostimulant drug-sensitized rats (funded by NSERC). Some schizophrenia-like symptoms can be produced and/or exacerbated by drugs of abuse such as amphetamine and phencyclidine. This project aims to understand the synaptic mechanisms of behavioural changes in rats that have been repeatedly treated with d-amphetamine.