The majority of excitatory glutamatergic synapses in the mammalian central nervous system (CNS) are located on postsynaptic dendritic spines, which contain all the essential components required for postsynaptic signaling and thus serve as a good indicator of synaptic connectivity. Many lines of in vivo imaging data have shown that neuronal circuits can be modified through de novo formation or loss of dendritic spines. Our early data show that spines turn over rapidly in adolescent mice but become remarkably stable in adults. In addition, sensory experience from whiskers promotes a net loss of spines by increasing the rate of spine elimination in barrel cortex. This synaptic loss occurs predominantly in adolescence and through NMDA receptor-dependent competitive mechanisms (Zuo et al., 2005).
While dynamics and morphological changes of dendritic spines are believed to provide a structural basis for synaptic plasticity, the molecular mechanisms regulating spine formation, stabilization and elimination remain unclear. Mutant mice with altered spine dynamics provide a good entry point to address this question. In the past a few years, my lab has been screening various mutant mouse lines (including cell adhesion molecules, signaling molecules as well as transcription and translating regulators) with selective defects different aspect of spine dynamics (such as spine formation or spine elimination), and some of them are directly associated with experience. We are currently analyzing these mice to dissect the upstream and downstream molecular machinery in regulating spine dynamism.
Zuo Y, Yang G, Kwon E and Gan WB (2005) Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex. Nature 436(7048):261-265. [PDF]
Zuo Y, Lin A, Chang P and Gan WB (2005) Development of long-term dendritic spine stability in diverse regions of cerebral cortex. Neuron 46(2):181-189. [PDF]
Fu M and Zuo Y (2011) Experience-dependent structural plasticity in the cortex. Trends Neurosci. 34(4):177-187. [PDF]
Yu X, Wang G, Gilmore A, Yee AX, Li X, Xu T, Smith SJ, Chen L, Zuo Y (2013) Accelerated experience-dependent pruning of cortical synapses in ephrin-A2 knockout mice. Neuron 80(1): 64-71 [PDF]
Chen C, Lu J, and Zuo Y (2014) Spatiotemporal dynamics of dendritic spines in the living brain. Front. Neuroanat. 8:28 [PDF]
Lu J, and Zuo Y (2017) Clustered structural and functional plasticity of dendritic spines. Brain Res. Bull.129:18-22 [PDF]
Martin PM, Stanley RE, Ross AP, Frietas AE, Moyer CE, Brumback AC, Iafrati J, Stapornwongkul KS, Dominguez S, Kivimae S, Mulligan KA, Pirooznia M, McCombie WR, Potash JB, Zandi PP, Purcell SM, Sanders SJ, Zuo Y, Sohal VS, Cheyette BNR (2016) DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling, Mol. Psych. [Epub ahead of print] [PDF]
Tija M, Yu X, Jammu LS, Lu J and Zuo Y (2017) Pyramidal neurons in different cortical layers exhibit distinct dynamics and plasticity of apical dendritic spines. Front. Neural Circuits 11:43 [PDF]
Zemmar A, Chen C-C, Weinmann O, Kast B, Vajda F, Bozeman J, Isaad N, Zuo Y* and Schwab ME* (2017) Oligodendrocyte- and neuron-specific Nogo-A restrict dendritic branching and spine density in adult mouse motor cortex. Cerebral Cortex.[Epub ahead of print] *equal contribution [PDF]