One of the most important features of the nervous system is its remarkable plasticity of synaptic connections throughout life. While synaptic rearrangements play pivotal roles in the formation of long-term memory and functional recovery after nerve injury, synaptic loss correlates directly with decline in cognitive performance in the elderly and is likely to be involved in the pathogenesis of neurodegenerative diseases. At present, very little is known about how synaptic changes take place in living animals.We are studying the mechanisms that regulate structural plasticity of synapses by taking advantage of Green Fluorescent Protein (GFP) expressing transgenic mice in which synaptic structures are labeled by GFP. Using confocal and two-photon microscopy, we have been able to image synapses of the same neuron over extended periods of time in both the central and peripheral nervous system of living mice. This ability to follow individual inter-neuronal synapses in vivo opens a direct window to study many interesting questions such as:
- How dynamic are synapses once they are formed?
- How does change in synaptic structure occur as a function of age?
- How does neuronal activity modulate synaptic structure?