Molecular Mechanisms of Activity-Dependent Synaptic Development and Plasticity
The long term goal of the work in our laboratory is to understand at a cellular and molecular level how neuronal activity regulates the formation and maturation of synapses both during brain development and in response to plasticity-inducing stimuli, and ultimately to use genetic model systems to investigate how defects in this process lead to cognitive and behavioral dysfunction.

We are taking two primary approaches to this problem. First we are studying the molecular mechanisms by which extrinsic factors like neuronal activity regulate intrinsic gene expression programs through the modulation of transcription factor function and chromatin structure. Second, we are studying the role of neural activity and activity-dependent expression of the neurotrophin Brain-Derived Neurotrophic Factor in GABAergic synaptogenesis. In both contexts we are using culture-based assays and RNA interference to characterize the transcriptional regulators and signaling pathways that direct synaptic development. In the future, mice bearing mutations of these proteins may be good candidates to provide animal models for complex disorders of cognitive and emotional development such as mental retardation and autism.

By studying the expression and activity of transcriptional regulators in the nervous system we hope to understand how these proteins modulate long-lasting neuronal responses to the environment. Shown above, the transcriptional repressor MeCP2 (red), the GABAergic interneuron marker parvalbumin (green) and nuclei (blue) in the hippocampus of an adult mouse.