Faculty: Amy J. Ramsey, PhD
General Research Areas: Animal models of schizophrenia, neuropharmacology, NMDA receptor biology.
Our laboratory is interested in studying schizophrenia using genetic mouse models of the disease with altered levels of neurotransmitter receptors and regulatory proteins. These models are studied at the molecular level, examining changes in gene expression and protein biology, and at the whole animal level, examining changes in behavioral pharmacology.
One of the principal efforts of our laboratory is to understand the physiological consequences of NMDA receptor deficiency using a genetic mouse model that expresses low levels of the receptor throughout the brain. The NMDA receptor is a subtype of glutamate neurotransmitter receptors that regulates the formation and maintenance of synaptic connections between neurons. It plays an important role in the way that neurons wire together and change the strength of synaptic connections with experience. It is also implicated in a number of disease states including schizophrenia, a devastating mental illness.
Our previous work has demonstrated that NMDA receptor deficient mice represent a model of schizophrenia, exhibiting behavioral abnormalities that can be partially reversed with antipsychotic drugs. More recent studies have focused on the biochemical composition of the synapse, and the resulting morphology of the postsynaptic spine. The goal of our efforts is to understand which proteins and signal transduction systems are altered when NMDA receptors are deficient. This knowledge may provide new insights into therapeutic treatments for schizophrenia, which can be experimentally tested in our model systems.
- Islam R, Trepanier MO, Milenkovic M, Horsfall W, Salahpour A, Bazinet RP, Ramsey AJ. (2017) Vulnerability to omega-3 deprivation in a mouse model of NMDA receptor hypofunction. npj Schizophrenia 3, article number: 12. doi:10.1038/s41537-017-0014-8.
- Funk AJ, Mielnik CA, Koene R, Newburn E, Ramsey AJ, Lipska BK, McCullumsmith RE. (2017) Postsynaptic density-95 isoform abnormalities in schizophrenia. Schizophrenia Bulletin doi: 10.1093/schbul/sbw173.
- Grannan MD, Mielnik CA, Gould RW, Moran SP, Ball J, Bubser M, Ramsey AJ, Abe M, Cho HP, Nance KD, Blobaum AL, Niswender CM, Conn PJ, Lindsley CW, Jones CK. (2016) Prefrontal cortex-mediated impairments in a genetic model of NMDA receptor hypofunction are reversed by the novel M1 PAM, VU6004256. ACS Chemical Neuroscience 7(12):1706-1716.
- Zurek AA, Kemp SWP, Aga Z, Walker S, Milenkovic M, Ramsey AJ, Sibille E, Scherer SW, Orser BA. (2016) a5GABAA receptor deficiency causes autism-like behaviors. Annals of Clinical and Translational Neurology 3(5):392-8.
- Korth C, Trossbach S, Bader V, Hecher L, Prikulis I, Pum M, Schäble S, de Souza Silva MA, Huston J, Su P, Ramsey AJ, Liu F, Masoud S, Boulat B, Chwiesko C, Sauvage M, Lohr K, Stout K, Miller GW, Weisshaupt A, Andreas Bauer, Godsave S, Peters P, Bilzer T, Steiner H, Seeman P, Brandon N, Poschmann G, Stühler K, Müller-Schiffmann A. (2016) Misassembly of full-length Disrupted-in-schizophrenia 1 (DISC1) protein is linked to altered dopamine homeostasis and behavioral deficits. Molecular Psychiatry 21(11):1561-1572.
- Masoud ST, Vecchio LM, Bergeron Y, Hossain MM, Bermejo MK, Kile B, Sotnikova TD, Siesser WB, Gainetdinov RR, Wightman RM, Caron MG, Richardson JR, Miller GW, Ramsey AJ, Cyr M, Salahpour A. (2015) Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and l-DOPA reversible motor deficits. Neurobiology of Disease 74:66-75.
- Ruddy RM, Milenkovic M, Chen YX, Ramsey AJ. (2015) Differential effects of NMDA receptor antagonists on spine density. Synapse 69(1):52-6.
- Bermejo MK, Milenkovic M, Salahpour A, Ramsey AJ. (2014) Preparation of protein from the synaptic plasma membrane and postsynaptic density by sucrose density gradient centrifugation. Journal of Visualized Experiments (91):e51896.
- Milenkovic M, Mielnik CA, Ramsey AJ. (2014) NMDA receptor deficient mice display sexual dimorphism in onset and severity of behavioural abnormalities. Genes, Brain, Behavior 13(8):850-62.
- Mielnik CA, Horsfall W, Ramsey AJ. (2014) Diazepam improves aspects of social withdrawal and neuron activation in NMDA receptor deficient mice. Genes, Brain, Behavior 13(7):592-602.
- Ferris MJ, Milenkovic M, Liu S, Mielnik CA, Beerepoot P, John CE, España RA, Sotnikova TD, Gainetdinov RR, Borgland SL, Jones SR, Ramsey AJ. (2014) Sustained N-methyl-d-aspartate receptor hypofunction remodels the dopamine system and impairs phasic signaling. European Journal of Neuroscience 40(1):2255-63.
- Medvedev IO, Ramsey AJ, Urs N, Bermejo KM, Sotnikova TD, Beaulieu JM, Gainetdinov RR, Salahpour A. (2013) D1 dopamine receptor coupling to PLC-beta regulates forward locomotion in mice. Journal of Neuroscience 33(46):18125-33.
Department of Pharmacology and Toxicology
Room 4302, Medical Sciences Building
1 King's College Circle