Abstract
Understanding brain structure and function, and the complex relationships between them, is one of the grand challenges of contemporary sciences. Thanks to their flexibility, optical techniques could be the key to explore this complex network. In this manuscript, we briefly review recent advancements in optical methods applied to three main issues: anatomy, plasticity and functionality. We describe novel implementations of light-sheet microscopy to resolve neuronal anatomy in whole fixed brains with cellular resolution. Moving to living samples, we show how real-time dynamics of brain rewiring can be visualized through two-photon microscopy with the spatial resolution of single synaptic contacts. The plasticity of the injured brain can also be dissected through cutting-edge optical methods that specifically ablate single neuronal processes. Finally, we report how nonlinear microscopy in combination with novel voltage sensitive dyes allow optical registrations of action potential across a population of neurons opening promising prospective in understanding brain functionality. The knowledge acquired from these complementary optical methods may provide a deeper comprehension of the brain and of its unique features.
Highlights
The brain is probably the most complex structure in the known universe, complex enough to coordinate movements, gather and organize lots of sensory data, perform abstract reasoning and develop new ideas
Understanding the mechanisms underlying brain function is one of the biggest challenges of contemporary science, considering the increasing social impact of neurological disorders, This is an Open Access article published by World Scientic Publishing Company
Dodt et al pioneered the application of light-sheet microscopy (LSM) coupled with optical clearing to image GFP-labeled mouse brains.[25]
Summary
The brain is probably the most complex structure in the known universe, complex enough to coordinate movements, gather and organize lots of sensory data, perform abstract reasoning and develop new ideas. Understanding the mechanisms underlying brain function is one of the biggest challenges of contemporary science, considering the increasing social impact of neurological disorders, This is an Open Access article published by World Scientic Publishing Company The exceptional features of the brain appear to emerge from the enormous number of units and links and from the ability of the network to adaptively \rewire" itself in response to external and internal stimuli.[2] The investigation of the structural and dynamical properties of this network poses several challenges in imaging technology, since brain activity spans many orders of magnitude both spatially (from nanometers to centimeters) and temporally (from milliseconds to months) Thanks to their °exibility in terms of spatial and temporal resolution, together with high specicity, optical methodologies have recently become very popular in neuroscience research.[3] In this paper, we will review specic optical microscopy strategies used to address three main questions in neuroscience, i.e., the micronscale anatomy of entire brains, the structural plasticity in vivo and the functional connectivity of intact neuronal networks
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