The Kelleher laboratory studies the molecular and cellular mechanisms underlying cognition and cognitive disorders. Our prior work established an essential role for translational regulation in long-lasting forms of synaptic plasticity and memory, and further defined an essential MAPK-dependent pathway coupling synaptic activation to the dendritic protein synthesis machinery. Current research projects are directed toward defining the molecular mechanisms regulating local protein synthesis in neurons, and understanding how these translational mechanisms contribute to normal cognition and the modification of synaptic connectivity in the mammalian brain. Examination of the role of defective translational control in the pathogenesis of specific neuropsychiatric disorders, particularly mental retardation and autism, is a closely related effort. In a complementary line of research, the laboratory is also investigating the molecular and cellular mechanisms responsible for neurodegenerative dementia, with a focus on the role of altered presenilin function in Alzheime?s disease and frontotemporal dementia. Due to the complexity of these problems, which span the gap from molecules to cognitive function, the laboratory employs a multidisciplinary approach, including conditional and inducible genetic manipulations in mice, biochemical, molecular and cell biological analysis, slice electrophysiology and mouse behavior.