The mammalian brain has billions of neurons each forming up to several thousand synaptic connections. Transmission of signals across the chemical synapses is essential for our abilities to process sensory information, generate behavioral responses, learn and remember. Deficits in synapse formation and synaptic plasticity have been implicated in a wide range of neurodegenerative and psychiatric disorders including Alzheimer’s disease, Parkinson’s disease, Autism Spectrum Disorders, Bipolar Disorder and Schizophrenia. Our laboratory at The Scripps Research Institute has two missions: to define the basic mechanisms underlying synaptic development and function and to elucidate the links between synaptic abnormalities and heritable disease.

In developing and adult brain, synaptic modifications shape the emerging neural circuits and play an essential role in information processing. We use a combination of mouse genetic, optical and electrophysiological methods to study the molecular basis of experience-dependent forms of synaptic plasticity. Our specific interests are focused on understanding how neurons secrete the soluble cues that regulate synaptic strength and how activity-dependent changes in secretion of these cues impact the expression of genes that build and modulate synapses in the cerebral cortex and hippocampus.

The second major research direction in the laboratory is focused on understanding how psychiatric disorders influence the synaptic properties of neural circuits in human brain. We are developing human neuronal disease models by reprogramming non-neuronal patient-specific cells into functional neurons. We hope that these systems will allow us to define the interplay between the genetic and physiological factors associated with disease and will facilitate the development of new therapeutic strategies.

Our research is funded by the National Institute of Mental Health, Novartis Advanced Discovery Institute, Dorris Neuroscience Fellowship program, Life Science Research Foundation, and The Japanese Society for Promotion of Science.