Gan Lab

SKIRBALL INSTITUTE
OF BIOMOLECULAR MEDICINE

Gan Lab

Structural Plasticity of synapses in vivo

Neurons in the brain
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?
In addition, we have developed the "DiOlistic" technique for rapid and complete labeling of a large number of neurons to study synaptic plasticity in the central nervous system. Using this technique, we have observed various synaptic abnormalities near amyloid plaques in transgenic mouse models of Alzheimer’s disease. We are currently investigating the mechanisms underlying these abnormal synaptic alterations that may occur early in the pathogenesis of Alzheimer’s disease.

Gan Lab
Structural Plasticity of synapses in vivo

	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? In addition, we have developed the "DiOlistic" technique for rapid and complete labeling of a large number of neurons to study synaptic plasticity in the central nervous system. Using this technique, we have observed various synaptic abnormalities near amyloid plaques in transgenic mouse models of Alzheimer’s disease. We are currently investigating the mechanisms underlying these abnormal synaptic alterations that may occur early in the pathogenesis of Alzheimer’s disease.