我们实验室的研究首次证明了大脑皮层的大部分树突棘能稳定存在于整个生命过程，并能作为长期信息存储的结构基础 (Grutzendler et al., Nature 2002; Zuo et al., Nature, 2005; Yang et al., Nature, 2009;Lai et al., Nature, 2012; Yang et al., Science, 2014; Cichon and Gan, Nature, 2015). 我们发现学习过程选择性诱发树突棘形成和消失。诱发形成的新树突棘和早期出生后形成的树突棘能作为长期记忆存储的结构基础。另外我们还研究了阿尔茨海默病的突触病理学，并首次证明纤维状淀粉样沉积与神经联结的大范围中断有关 (Tsai et al., 2004 Nature Neuroscience)。
Structural plasticity of synapses
We are interested in understanding synaptic structure and function in the living brain.Specifically,we examine the development and maintenance of synapses with various techniques including transcranial two-photon imaging, molecular biology and electrophysiology.We also investigate how to prevent abnormal synapse loss in mouse models 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:
(1) How dynamic are synapses once they are formed?
(2) How does change in synaptic structure occur as a function of age?
(3) How does neuronal activity modulate synaptic structure?