Abstract
Mapping mammalian synaptic connectivity has long been an important goal of neuroscience because knowing how neurons and brain areas are connected underpins an understanding of brain function. Meeting this goal requires advanced techniques with single synapse resolution and large-scale capacity, especially at multiple scales tethering the meso- and micro-scale connectome. Among several advanced LM-based connectome technologies, Array Tomography (AT) and mammalian GFP-Reconstitution Across Synaptic Partners (mGRASP) can provide relatively high-throughput mapping synaptic connectivity at multiple scales. AT- and mGRASP-assisted circuit mapping (ATing and mGRASPing), combined with techniques such as retrograde virus, brain clearing techniques, and activity indicators will help unlock the secrets of complex neural circuits. Here, we discuss these useful new tools to enable mapping of brain circuits at multiple scales, some functional implications of spatial synaptic distribution, and future challenges and directions of these endeavors.
Highlights
It is no exaggeration to state that the beautiful drawings of the visionary Spanish neuroanatomist Santiago Ramon Cajal (1852–1934, Nobel Laureate 1906) illustrating neuronal structure and brain architecture, set the standard for neuroanatomy in the last century
We summarize the currently available methods to enable mapping of brain circuits at the scale levels: (1) Non-invasive brain imaging methods, i.e., magnetic resonance imaging (MRI) and positron emission tomography (PET) widely used for the whole human brain, provide information about region-to-region connectivity at millimeter-resolution (Catani and Thiebaut de Schotten, 2008)
Comprehensive Micro-Scale Connectome with Triple Combination of Array Tomography (AT), mammalian GFP-Reconstitution Across Synaptic Partners (mGRASP), and Activity Sensors Given the distinctive advantages and pitfalls of both AT and mGRASP, we propose the combination of these two technologies into a powerful tool for determining the micro-scale connective synaptome
Summary
It is no exaggeration to state that the beautiful drawings of the visionary Spanish neuroanatomist Santiago Ramon Cajal (1852–1934, Nobel Laureate 1906) illustrating neuronal structure and brain architecture, set the standard for neuroanatomy in the last century. Mapping these structures requires advanced neuronal labeling, imaging, and reconstructing techniques that provide high-resolution in multiple scales (Box 1; Kleinfeld et al, 2011; Wickersham and Feinberg, 2012; Morgan and Lichtman, 2013; Yook et al, 2013). Of several advanced LM-based connectome technologies, array tomography (AT) and mammalian GFP-Reconstitution Across Synaptic Partners (mGRASP) can provide relatively high-throughput mapping synaptic connectivity at multiple scales.
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