This project is directed at understanding the structure and function of synapses in the developing and mature brain, by quantitative and three-dimensional analysis of the structure, connectivity, and plasticity of presynaptic, postsynaptic, and glial elements. Such knowledge is important for understanding the role of synapses in normal brain functions such as learning and memory, and the effects of injury and disease on these functions. The informatics objective is to improve the methods of quantitative analysis and availability of ultrastructural tutorials and anatomical data on the web, which has significant relevance for the neuroscience objectives as well. Additional neuroscience objectives are to use the new informatics tools in ongoing research projects on synaptogenesis, long-term potentiation (LTP), and long-term depression (LTD), which are two of the most important synaptic models of learning and memory.
The specific aims are: 1) Improve the acquisition, alignment, segmentation, and 3D reconstruction of serial sections from brain. 2) Enhance software for the public domain, that is internet-accessible and third-party extensible to support development of the database and neuroscience research. 3) Expand our internet-accessible repository of synaptic and perisynaptic anatomy that serves as a community resource for connecting the molecular to the neuron levels of analyses. 4) Use the new reconstruction tools to determine the impact of blocking synaptic transmission on the structure of spines, synapses and their associated astroglial processes in adult rat hippocampal slices. 5) Use the new reconstruction tools to determine whether synapse number, synaptic size, or the number of docked presynaptic vesicles are regulated in opposite directions during LTP and LTD at immature or mature hippocampal neurons. In addition, use the new tools to evaluate whether local protein synthesis, indicated by polyribosomes, or membrane recycling, indicated by endosomes, mediate the structural changes at synapses that have undergone LTP or LTD.
|Bell, Maria Elizabeth; Bourne, Jennifer N; Chirillo, Michael A et al. (2014) Dynamics of nascent and active zone ultrastructure as synapses enlarge during long-term potentiation in mature hippocampus. J Comp Neurol 522:3861-84|
|Edwards, John; Daniel, Eric; Kinney, Justin et al. (2014) VolRoverN: enhancing surface and volumetric reconstruction for realistic dynamical simulation of cellular and subcellular function. Neuroinformatics 12:277-89|
|Kuwajima, Masaaki; Mendenhall, John M; Harris, Kristen M (2013) Large-volume reconstruction of brain tissue from high-resolution serial section images acquired by SEM-based scanning transmission electron microscopy. Methods Mol Biol 950:253-73|
|Kinney, Justin P; Spacek, Josef; Bartol, Thomas M et al. (2013) Extracellular sheets and tunnels modulate glutamate diffusion in hippocampal neuropil. J Comp Neurol 521:448-64|
|Kuwajima, M; Spacek, J; Harris, K M (2013) Beyond counts and shapes: studying pathology of dendritic spines in the context of the surrounding neuropil through serial section electron microscopy. Neuroscience 251:75-89|
|Cui-Wang, Tingting; Hanus, Cyril; Cui, Tao et al. (2012) Local zones of endoplasmic reticulum complexity confine cargo in neuronal dendrites. Cell 148:309-21|
|Cao, Guan; Harris, Kristen M (2012) Developmental regulation of the late phase of long-term potentiation (L-LTP) and metaplasticity in hippocampal area CA1 of the rat. J Neurophysiol 107:902-12|
|Bowden, Jared B; Abraham, Wickliffe C; Harris, Kristen M (2012) Differential effects of strain, circadian cycle, and stimulation pattern on LTP and concurrent LTD in the dentate gyrus of freely moving rats. Hippocampus 22:1363-70|
|Bourne, Jennifer N; Harris, Kristen M (2012) Nanoscale analysis of structural synaptic plasticity. Curr Opin Neurobiol 22:372-82|
|Shi, Bitao; Bourne, Jennifer; Harris, Kristen M (2011) SynapticDB, effective web-based management and sharing of data from serial section electron microscopy. Neuroinformatics 9:39-57|
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