Zito, Karen - University of California, Davis - College of Biological Sciences

研究领域

Cellular and Molecular Mechanisms of Synaptic Plasticity The goal of our research is to understand at the cellular and molecular level how synaptic connections form during development, how they are modified by sensory experience and altered in disease. Most of the excitatory synaptic connections in the cortex occur on dendritic spines, tiny protrusions that extend from the dendritic membrane. Dendritic spines are highly dynamic during development both in vitro and in vivo; periods of high motility coincide with synapse formation. Spine motility, driven by actin dynamics, is thought to allow the postsynaptic neuron to explore and sample presynaptic partners. In addition, alterations of spine dynamics and stability have been observed in response to sensory experience, leading to the hypothesis that these anatomical changes underlie the adaptive remodeling of cortical circuits. The identification and characterization of the molecules and mechanisms that control spine morphogenesis will be a crucial step toward understanding the formation and plasticity of cortical circuits. Our approach to this problem combines time-lapse imaging to observe nascent spine formation, and fluorescence recovery after photobleaching (FRAP) to measure protein dynamics, with molecular manipulations of synaptic proteins to decipher their roles in the growth of dendritic spines and synapses. In addition, we use physiological measurements in combination with two-photon uncaging of glutamate to examine the function of nascent synapses at the single synapse level.

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Stein IS, Gray J, Zito K. (2015) Non-ionotropic NMDA receptor signaling drives activity-induced dendritic spine shrinkage. J Neurosci. 35:12303-8. Oh WC, Parajuli LK, Zito K. (2015) Heterosynaptic structural plasticity on local dendritic segments of hippocampal CA1 neurons. Cell Reports 10: 162-9. Oh WC, Hill TC, Zito K. (2013) Synapse-specific and size-dependent mechanisms of spine structural plasticity accompanying synaptic weakening. PNAS 110: E305-12. Hill TC and Zito K (2013) LTP-induced long-term stabilization of individual nascent dendritic spines. J Neurosci. 33: 678-86. Hamilton AM, Oh WC, Vega-Ramirez H, Stein IS, Hell JW, Patrick GN, Zito K. (2012) Activity-dependent growth of new dendritic spines is regulated by the proteasome, Neuron, 4: 1023-30. Woods GF, Oh WC, Boudewyn LC, Mikula SK, Zito K. (2011) Loss of PSD-95 enrichment is not a prerequisite for spine retraction. J Neurosci. 31: 12129-38. Zito K, Scheuss V, Knott G, Hill T, Svoboda K. (2009) Rapid functional development of nascent dendritic spines. Neuron 61: 247-58. Woods G and Zito K (2008) Preparation of gene gun bullets and biolistic transfection of neurons in slice culture. JoVE 12, http://www.jove.com/index/Details.stp?ID=675, doi: 10.3791/675.