Ozlem B Gunal

Ozlem B Gunal, MD, PhD

  • ASSISTANT PROFESSOR | Neuroscience

My overall research goal is to understand the mechanisms of synaptic plasticity and remodeling in the nervous system and the role of these processes in neurodegenerative disorders. I use electrophysiological techniques for recording of neural activity in vivo, in brain slice preparations in vitro, from co-cultured explants, and from dissociated neuronal cultures, as well as collaborative methods including biochemical, molecular biological, and imaging techniques. My model system has primarily been the hippocampus, which is unique in that it appears to mediate information flow between a variety of different sensory inputs and the cortex, and is an area of the brain that plays an important role in learning and memory. Changes in hippocampal function appear to be critical in the cognitive impairment observed in neurodegenerative and neuropsychiatric illnesses. Long-term potentiation, which is viewed as a synaptic model of memory, is one example of how synaptic connections can be altered by neural activity. There are a number of proteins that may directly modify synaptic function and structure, and affect long-term change. My previous work characterized the role of the cell adhesion molecule N-cadherin and degradation of extracellular matrix by MMP-9, in synaptic plasticity and remodeling.

 Disruptions in synaptic plasticity and mutations in number of synaptic proteins have long been linked to various neuropsychiatric disorders including autism and related disorders. My ongoing projects are on the mouse models that reflect these genetic alterations implicated in autism and schizophrenia, which may help to understand the pathogenesis of these disorders. One of them is a model with a reduced expression of a synaptic scaffolding protein Shank3, which is a critical part of the core of the postsynaptic density. Haploinsufficiency of the protein causes Phelan-McDermid Syndrome, which is strongly associated with autism. Another one is a mouse model with reduced expression of Cyfip1, which is a Fmrp binding protein, the latter that functions in translational control and the deficiency of the protein causes Fragile X Syndrome. My focus here is to understand the changes in synaptic plasticity and cellular mechanisms of learning and memory in these disorders, identify the deficits in multiple common/different pathways, target proteins, which may contribute to the pathophysiology of autism and related disorders, and then to attempt interventions in the model systems.