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A critical neuroscience challenge is the need to optically image and manipulate neural activity with high spatiotemporal resolution over large brain volumes. The last three decades have seen the development of calcium imaging to record activity from neuronal populations, as well as optochemistry and optogenetics to optically manipulate neural activity. These methods are typically implemented with wide-field or laser-scanning microscopes. https://www.selleckchem.com/products/cfi-400945.html While the former approach has a good temporal resolution, it generally lacks spatial resolution or specificity, particularly in scattering tissues such as the nervous system; meanwhile, the latter approach, particularly when combined with two-photon excitation, has high spatial resolution and specificity but poor temporal resolution. As a new technique, holographic microscopy combines the advantages of both approaches. By projecting a holographic pattern on the brain through a spatial light modulator, the activity of specific groups of neurons in 3D brain volumes can be imaged or stimulated with high spatiotemporal resolution. In a combination of other techniques such as fast scanning or temporal focusing, this high spatiotemporal resolution can be further improved. Holographic microscopy enables all-optical interrogating of neural activity in 3D, a critical tool to dissect the function of neural circuits.Various light sources have been developed for the application of optical stimulation in the optogenetics field. Light transmission inside living tissue is limited to a distance of a few millimeters; hence, it is necessary to insert the light source near the nerve tissue to be stimulated. If a device is rigid, it causes mechanical stimulation to act on the nerve tissue. The application of mechanical stimulation may induce inflammation, obstructing neural activity. Fabricating such a device out of a soft material can prevent mechanical stimulation of cells and mitigate biological reactions such as inflammation or encapsulation. Minimizing the sizes of LED and other light sources as much as possible and mounting them on a flexible substrate can provide the entire device with flexibility. Micro-LEDs can be reduced to a size almost comparable to that of a cell and it has even been reported that some have been mounted on the tip of needle-shaped devices inserted into living tissue. A device using organic semiconductors is sufficiently soft to be bent, which is a characteristic not observed in inorganic semiconductors. Using organic LEDs can realize wide-area flexible light-emitting surfaces and they are widely anticipated to be the next generation of light sources. This chapter introduces technologies used to manufacture these soft light sources and examples of optical stimulation devices that incorporate them.Optical and electronic neural interface devices based on CMOS technology are presented. Concept, design strategy, and fabrication of the CMOS-based optoelectronic neural interface devices are described. The devices are based on a technology of implantable CMOS image sensor. To realize addressable local optical stimulation, blue light-emitting diode array chip was integrated on the implantable CMOS image sensors. Functional demonstrations of the devices are also presented. Optical stimulation capability was demonstrated in both in vitro and in vivo experiments. Further perspective including wireless device architecture is also presented.Although multiphoton microscopy enables optical control and monitoring of neural activity with single cells resolution over a depth of several hundreds of micrometers, the scattering nature of the brain tissue requires implantable optical neural interfaces to access subcortical structures. If micro light-emitting devices (μLEDs) and solid-state waveguides represent important technological advancements for the field, multimodal optical fibers (MMFs) are still the most diffused tool in neuroscience labs to interface with deep regions of the brain. At a first glance, MMFs can be seen as very limited systems. However, new studies and discoveries in optics, photonics, and technological solutions for their application to neuroscience research have enabled applications of MMF where competing technologies fail. In this framework, the chapter starts with a description of optical neural interfaces based on MMF, with specific reference on recent works analyzing the performances of this approach to deliver and collect light from scattering tissue. The discussion then focuses on how peculiar features of MMFs can be exploited to obtain unconventional applications, including brain imaging through a single multimode fiber, multifunctional neural interfaces, and depth-resolved light delivery and functional fluorescence collection.Epilepsy is a disease characterized by seizures arising from paroxysmal and self-limited hypersynchrony of neurons. However, the mechanism by which the normal brain develops epilepsy, which involves a chronic process of structural and morphological changes known as epileptogenesis, is not fully understood. Optogenetics involves the use of genetic engineering and optics to monitor or control nerve cell activity. Compared to classical electrophysiological experiments, the application of optogenetics in epilepsy research has many advantages because it allows selective photic stimulation of cell types and electrical observation without introducing artifacts.The loss of photoreceptor cells caused by retinal degenerative diseases leads to blindness. The optogenetic approach for restoring vision involves converting the surviving inner retinal neurons into photosensitive cells, thus imparting light sensitivity to the retina following the loss of photoreceptor cells. Our first demonstration of the feasibility of such an approach involved expressing ChR2 in the retinal ganglion cells of blind mice; since then, optogenetic vision restoration has been demonstrated by using a variety of optogenetic tools, especially microbial channelrhodopsins (ChRs). A ChR-based optogenetic therapy for treating blindness has advanced to clinical trials. In this chapter, we review our early proof-of-concept study of optogenetic vision restoration. We also discuss our studies for developing better ChR tools and for restoring intrinsic visual processing features in retinas with degenerated photoreceptors.

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