Light Up the Brain: The Application of Optogenetics in Cell-Type Specific Dissection of Mouse Brain Circuits

Abstract

The exquisite intricacies of neural circuits are fundamental to an animal's diverse and complex repertoire of sensory and motor functions. The ability to precisely map neural circuits and to selectively manipulate neural activity is critical to understanding brain function and has, therefore been a long-standing goal for neuroscientists. The recent development of optogenetic tools, combined with transgenic mouse lines, has endowed us with unprecedented spatiotemporal precision in circuit analysis. These advances greatly expand the scope of tractable experimental investigations. Here, in the first half of the review, we will present applications of optogenetics in identifying connectivity between different local neuronal cell types and of long-range projections with both in vitro and in vivo methods. We will then discuss how these tools can be used to reveal the functional roles of these cell-type specific connections in governing sensory information processing, and learning and memory in the visual cortex, somatosensory cortex, and motor cortex. Finally, we will discuss the prospect of new optogenetic tools and how their application can further advance modern neuroscience. In summary, this review serves as a primer to exemplify how optogenetics can be used in sophisticated modern circuit analyses at the levels of synapses, cells, network connectivity and behaviors.

Extrinsic neuromodulation in the rodent olfactory bulb

“…First results defining the input-output relations of different brain centers indicate that there are great differences between neuromodulatory systems, with, e.g., the LC rather resembling a homogenous integrator and broadcaster of information (Schwarz et al 2015 ), while input-output relations in the BF seem to be much more specific (Gielow and Zaborszky 2017 ). Other technical advances in, e.g., the development of faster, more sensitive optogenetic tools for cell type-specific dissection of brain circuits (Lee et al 2020 ), increasing spatial resolution for deep brain imaging (Vasquez-Lopez et al 2018 ), and enhancing sensitivity and expression of genetically coded calcium dyes (Dana et al 2019 ) will help to advance our knowledge on the specific functions of different neuromodulatory systems in olfactory guided behaviors.…”

Novel Tools and Investigative Approaches for the Study of Oligodendrocyte Precursor Cells (NG2-Glia) in CNS Development and Disease

“…Novel techniques of improving our understanding of OPC functions include optogenetic, intra cellular ion signaling activity and imaging (Friess et al, 2016 ; Ortolani et al, 2018 ; Zhang M. et al, 2019 ; Heredia et al, 2020 ; Marisca et al, 2020 ). Optogenetics involves the use of light to modulate cells expressing a light-sensitive ion channel, and has historically been used primarily to modulate neuronal activity (Lee et al, 2020 ). Typically, a photo-sensitive variant of channel-rhodopsin 2 (ChR2) is used.…”

Insights Into Central Nervous System Glial Cell Formation and Function From Zebrafish

“…In parallel to forward and reverse genetic approaches to assess gene function, the field of optogenetics has revolutionised neuroscience by allowing researchers to take control of the functional firing and signalling properties of neurons and glial cells ( Warden et al, 2012 ; Cho et al, 2016 ; Kato et al, 2019 ; Mu et al, 2019 ; Lee et al, 2020 ). A principal set of tools in optogenetics are light-sensitive ion channels, which can be activated to control the electrical activity of cells.…”