cohen-coryA major focus of our research has been to elucidate cellular and molecular events that guide the development of synaptic connectivity in the living brain. To date, most of the understanding of synapse formation and stabilization comes from extensive studies performed in culture or using the neuromuscular junction as model systems. Recent advances in methodologies including real-time imaging of living neurons have begun to provide new insight into the cellular, molecular, and activity-dependent processes that guide synaptogenesis in the central nervous system. Our laboratory has contributed significantly to the understanding of molecular and cellular mechanisms of synaptogenesis by recording the visual system of the Xenopus laevistadpole in real time in vivo. We examine how neurotrophins modulate retinal ganglion cell development, differentiation, and synaptic connectivity with brain neurons. Neurotrophins and their receptors participate in the development of synaptic connectivity at multiple levels. In the visual system the neurotrophin brain-derived neurotrophic factor (BDNF) has been shown to exert various developmental influences, from guiding the morphological differentiation of neurons to controlling the functional plasticity of visual circuits. We have established the cellular mechanisms by which BDNF and neuronal activity modulate axon and dendritic arborization and determined how these in vivo, dynamic events relate to synapse formation by using the Xenopus visual system as a model. The expression of green fluorescent protein (GFP)-labeled synaptic components combined with real-time imaging of neurons has provided us with a powerful tool to reveal events that take place during synaptogenesis.  By visualizing synaptic sites in central neurons in live, developing tadpoles we have provided the first direct evidence that synaptogenesis in the central nervous system is dynamic and is directly correlated with branching and remodeling of axon terminal arbor. Moreover, our studies have also revealed the existence of a coincident mechanism of synaptogenesis in axon and dendritic arbors, which is differentially modulated by BDNF.

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