Neurobiology, Physiology and Behavior
Development and Plasticity of Neural Circuits
Mechanisms of experience-dependent 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 experience, and how they are altered in disease. Most of the excitatory synaptic connections in the cerebral 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 with molecular manipulations of synaptic proteins to decipher their roles in the growth of dendritic spines and synapses. In addition, we use electrophysiological measurements in combination with two-photon uncaging of glutamate to examine the function of nascent synapses at the single synapse level.
Lambert JT, Hill TC, Park DK, Culp JH, Zito K (2017) Protracted and asynchronous accumulation of PSD95-family MAGUKs during maturation of nascent dendritic spines. Dev Neurobiol. 2017 Apr 7. doi: 10.1002/dneu.22503. [Epub ahead of print]
Stein IS, Gray JA, Zito K (2015) Non-Ionotropic NMDA Receptor Signaling Drives Activity-Induced Dendritic Spine Shrinkage. J Neurosci.35(35):12303-8.
Oh WC, Parajuli LK, Zito K (2015) Heterosynaptic structural plasticity on local dendritic segments of hippocampal CA1 neurons. Cell Reports 10(2):162-9.
Hill TC, 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 74:1023-30
Woods G, Oh WC, Boudewyn LC, Mikula SK, Zito K (2011) Loss of PSD-95 is not a prerequisite for spine retraction. J Neurosci 31: 12129-38.
Zito K, Scheuss V, Knott G, Hill T, Svoboda K (2009) Rapid development of glutamatergic synapses on nascent spines, Neuron 61: 247-258.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.
Biochemistry, Molecular, Cellular and Developmental Biology