The long-term goal of Dr. Lu Chen's research is to understand the cellular and molecular mechanisms that underlie synapse function during behavior in the developing and mature brain, and how synapse function is altered during mental retardation. In this broad research area, Dr. Chen is specifically interested in the homeostatic control of synaptic strength, the role of postsynaptic protein translation in this control, and the impairment of synapses in Fragile X syndrome that involves changes in postsynaptic protein translation and synaptic strength.
Dr. Chen's lab recently discovered a role of all-trans retinoic acid (RA) in regulating synapse formation and synaptic strength, which they identified during studies of homeostatic synaptic plasticity. They found that RA is a potent activator of synaptic strength in mature neurons. Neuronal synthesis of RA is regulated by activity. When neuronal activity is blocked, RA synthesis is strongly stimulated. When applied directly, RA is sufficient to rapidly increase synaptic strength. Moreover, when they blocked RA synthesis in neurons, they abolished the increase in synaptic strength induced by activity blockade. Taken together, these results reveal a central role of RA in mediating activity blockade-induced increases in synaptic strength, and suggest that in adult brain, RA functions as a novel diffusible messenger that regulates synaptic transmission.
Some of the Chen lab's current research focuses include:
- Synaptic signaling mechanisms of RA - dissecting the molecular pathways for synaptic RA signaling, understanding the role of RA in the mature brain in mediating homeostatic and potentially other forms of synaptic plasticity, and exploring the function of RA in animal learning and behavior.
- Synaptic dysfunction in Fragile-X Syndrome - understanding the role of Fragile-X mental retardation protein in synaptic RA signaling, and studying synaptic functions in neurons derived from Fragile-X patients.
- Oxidative stress and synaptic dysfunction – understanding how glial and neuronal antioxidant responses to oxidative stress protect neuronal function, and which processes may be compromised in neurological disorders.
