A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Dr. LalitK.Srivastava, PhD
Douglas Mental Health University Institute
6875 LaSalle Blvd
The major goal of Dr. Srivastava’s 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.
Undergraduate: BSc Biology, University of Allahabad, India
Canadian College of Neuropsychopharmacology
Society for Neuroscience, Washington, DC
Baharnoori M, Brake W, Srivastava LK, Prenatal immune challenge induces developmental changes in the morphology of pyramidal neurons of the prefrontal cortex and hippocampus in rats. Schizophrenia Res. 2009;107:99-109.
Bhardwaj SK, Baharnoori M, Sharif-Askari B, Kamath A, Williams S, Srivastava LK. Behavioral characterization of dysbindin-1 deficient sandy mice. Behav. Brain Res. 2009;197:435-441.
Al-Khairi A, Baharnoori M, Kamath A, Bhardwaj SK, Srivastava LK. Altered expression and alpha-1 adrenergic receptor mediated activity of Protein Kinase C in the prefrontal cortex of rats with neonatal ventral hippocampus lesions. Synapse. 2009 Dec;63(12):1051-9.
Kamath A, Bhardwaj SK, Srivastava LK. Enhanced alpha-1 adrenergic sensitivity in sensorimotor gating deficits in neonatal ventral hippocampus lesioned rats. Int. J. Neuropsychopharmacol. 2008;11:1085-1096.
Bhardwaj SK, Cassidy C, Srivastava LK. Alterations in syntaxin 1B mRNA in the nucleus accumbens of amphetamine-sensitized rats. Int. J. Neuropsychopharmacology. 2006;9:751-759.
Seeman P, Weinshenker D, Quirion R, Srivastava LK, Bhardwaj SK, Grandy DK, Premont R, Sotnikova T, Boksa P, El-Ghundi M, O’Dowd BF, George SR, Perreault ML, Mannisto PT, Robinson S, Palmiter RD,Tallerico T, Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis. Proc. Natl. Acad. Sci. (U.S.A.). 2005;102:3513-3518.
Flores G, Silva-Gómez AB, Zaldivar Z, Alquicer G, Bhardwaj SK, Stewart J, Quirion R, Srivastava LK. Alteration in dendritic morphology of prefrontal cortical and nucleus accumbens neurons in adult rats following neonatal excitotoxic lesions of the ventral hippocampus. Neuroscience. 2005;133:463-470.
Marcotte ER, Pearson D, Srivastava LK. Animal models of schizophrenia: a critical review. J. Psychiatr. Neurosci. 2001;26:395-410.
Flores G, Barbeau D, Quirion R, Srivastava LK. Decreased binding of dopamine D3 receptors in limbic subregions following neonatal bilateral lesion of rat hippocampus. J. Neurosci. 1996;16:2020-2026.
Barbeau D, Liang JJ, RobitailleY, Quirion R, Srivastava LK. Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brain. Proc. Natl. Acad. Sci., U.S.A. 1995;92:2785-2789.