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.
Highlights
In the past decades, numerous newly developed techniques have greatly assisted in dissecting connectivity and function of the brain
Using this so-called ChR2-assisted circuit mapping (CRACM), the authors (Petreanu et al, 2007) systematically examined the strength of long-range callosal innervation received by neurons in individual layers of the barrel cortex and found that laminar specificity of this long-range cortical innervation is identical to local innervation (Petreanu et al, 2007)
This study demonstrated that the CRACM method can reliably drive projection-specific inputs without the need to preserve their tracts in slices
Summary
Numerous newly developed techniques have greatly assisted in dissecting connectivity and function of the brain. Only a handful of them have influenced and advanced modern neuroscience as heavily as optogenetics This state-of-the-art technique utilizes light-sensitive channels or pumps, known as opsins, to manipulate the activity of neurons. When it is combined with the Cre-Lox recombinase system, it provides a spatiotemporally precise method to reversibly turn on and off the activity of genetically defined or projection-specific groups of neurons. We will first highlight the use of optogenetics in the investigation of neural connectivity, both within and between brain regions, and its applications in identifying the functional roles of specific neural circuit components in behavior and physiology. Most of the examples in this review come from studies of sensory and motor systems, their diverse experimental designs and underlying principles are potentially useful for advancing our understanding of the structure and function of other brain circuits
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