![]() ![]() In many regions of the brain, excitatory synaptic contacts are formed on tiny dendritic protrusions known as dendritic spines ( Harris and Weinberg, 2012 Frotscher et al., 2014 Parajuli et al., 2017 Parajuli, 2018). Understanding the precise ultrastructure of synapses is essential to unravel the intricate neuronal circuitry and physiological functions of the brain. With a particular focus on dendritic spine synapses in the rodent brain, we discuss various key studies that have highlighted the structural diversity of spines, the principles of their organization in the dendrites, their presynaptic wiring patterns, and their activity-dependent structural remodeling. Here, we review studies that have been instrumental in determining the three-dimensional ultrastructure of synapses. The challenges of low throughput EM imaging have been addressed to an appreciable degree by the development of automated EM imaging tools that allow imaging and reconstruction of dendritic segments in a realistic time frame. While volumetric imaging of synapses can be routinely obtained from the transmission EM (TEM) imaging of ultrathin sections, it requires an unimaginable amount of effort and time to reconstruct very long segments of dendrites and their spines from the serial section TEM images. Furthermore, a complete three-dimensional reconstruction of an individual synaptic profile is required for the precise quantitation of different parameters that shape synaptic transmission. Although conventional light microscopic techniques have substantially contributed to our ever-increasing understanding of the morphological characteristics of the putative synaptic junctions, EM is the gold standard for systematic visualization of the synaptic morphology. A quantitative understanding of synaptic ultrastructure also serves as a basis to estimate the relative magnitude of synaptic transmission across individual circuits in the brain. 2Advanced Research Institute for Health Science, Juntendo University, Tokyo, JapanĮlectron microscopy (EM)-based synaptology is a fundamental discipline for achieving a complex wiring diagram of the brain.1Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan.Laxmi Kumar Parajuli 1* Masato Koike 1,2* ![]()
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