on-ionotropic NMDA receptor signaling alters structural plasticity of dendritic spines in a mouse model of schizophrenia by Deborah Park

Deborah Park

UC Davis | Nordstrom Stores Endowment Fund

My research investigates the cellular and molecular mechanisms that allows us to learn and form memories, as well as how this same mechanism can be implicated in the development of neurological or psychiatric disorders. Structural modification of small structures on brain cells called dendritic spines are integral for memory formation and are altered in disorders such as schizophrenia. By using a mouse model, part of my research investigates the potential mechanism as to how spine loss occurs in the development of schizophrenia.


The structural modification of dendritic spines on neurons, which includes growth and shrinkage, is an important process for memory formation. Both types of structural changes are mediated by the activation of proteins called NMDARs that are present on the spines. Schizophrenia is a psychiatric disorder associated with spine loss and reduced levels of d-serine. As simultaneous binding of endogenous chemicals, glutamate and d-serine, to NMDARs is required for spine growth, but the binding of glutamate alone instead results in spine shrinkage in a process called non-ionotropic NMDAR signaling, our lab hypothesized that lowered d-serine levels associated with schizophrenia enhances non-ionotropic NMDAR signaling to promote shrinkage and loss of spines instead of growth. Using a mouse model of schizophrenia that cannot produce d-serine, our results indeed demonstrate a bias for spine shrinkage over growth. Our research supports a model of novel molecular mechanism of schizophrenia that lowered d-serine levels enhances non-ionotropic NMDAR signaling to promote spine shrinkage that could play a role in spine loss observed with the disorder.


6 + 6 =