Mapping mammalian synaptic connectivity
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Cellular and Molecular Life Sciences
Review
Mapping mammalian synaptic connectivity Chaehyun Yook · Shaul Druckmann · Jinhyun Kim
Received: 27 February 2013 / Revised: 17 June 2013 / Accepted: 24 June 2013 © The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract Mapping mammalian synaptic connectivity has long been an important goal of neuroscientists since it is considered crucial for explaining human perception and behavior. Yet, despite enormous efforts, the overwhelming complexity of the neural circuitry and the lack of appropriate techniques to unravel it have limited the success of efforts to map connectivity. However, recent technological advances designed to overcome the limitations of conventional methods for connectivity mapping may bring about a turning point. Here, we address the promises and pitfalls of these new mapping technologies. Keywords Synaptic connectivity · Brainbow · Array tomography · mGRASP · Trans-synaptic tracer · Neurological disorders
Introduction More than a century ago, the visionary Spanish neuroanatomist Santiago Ramón Cajal (Nobel Laureate 1906) proposed what is often called the “neuron-doctrine,” the idea that neurons are the structural and functional units of the brain, and guided by this idea, proceeded to explore the C. Yook · J. Kim (*) Center for Functional Connectomics (CFC), L7‑7205, Korea Institute of Science and Technology (KIST), 39‑1 Hawolgokdong, Seongbukgu, Seoul 136‑791, Korea e-mail: [email protected] C. Yook Department of Biological Science, KAIST, Daejeon, Korea S. Druckmann Howard Hugh Medical Institute, Janelia Farm Research Campus, Ashburn, USA
complex architecture of neuronal networks [1, 2]. Neurons in networks communicate with one another through a special bridge-like structure called a synapse. Neuronal connections were traditionally determined by electrophysiological measurement from linked pairs of cells to determine the strength as well as the existence of a synapse, yet this approach has a very low throughput [3]. To this day, neuroscientists continue to seek new high-throughput ways to investigate neuronal circuits by mapping synaptic connectivity [4–10]. Recently, in 2005, the terms “connectome” and “connectomics” were coined and have since been widely used to describe this effort [11] (“-ome” as an analogy to “genome” is taken to signify complete maps of connections in a brain or a brain area). In 2009, the Human Connectome Project was launched by the National Institutes of Health (http://www.humanconnectomeproject. org) with the goal of building macro-scale descriptions of structural and functional connectivity in healthy human brains (strictly speaking, it would have been better named the “projectome” since the methods used in the Human Connectome Project can provide only macro-level profiles of nerve bundle projections); these profiles can be used to predict the probability of connectivity but not specific connections between given cells [9, 12, 13], and, increasingly, scientific endeavors are underw
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