BRAIN EAGER: Three Dimensional Optical Control of Neuronal Circuits during Behavior

Cold Spring Harbor Laboratory, Cold Spg Hbr NY

Investigators

Abstract

A central goal of systems neuroscience is to describe behaviors in terms of the neuronal circuits that control them. This constitutes a monumental challenge in the mammalian brain because behaviors are thought to rely on widely distributed neural representations, which are technically difficult to monitor at large scales or to manipulate at cellular resolution. This research will implement, optimize, and ultimately broadly distribute via online repositories and workshops, a three-dimensional, two-photon microscope, exploiting patterned illumination strategies for fast manipulation and monitoring of large neuronal populations in behaving animals. First, the PI will implement and optimize a dual photo-stimulation system to enable both precise two-dimensional illumination across wide fields of view using a digital micro-mirror device, as well as high-resolution three-dimensional stimulation using digital holography. Photo-stimulation will be combined with two photon resonant scanning imaging to achieve fast sampling rate of hundreds of neurons across large brain volumes. Second, these technologies will be demonstrated for in vivo use, in head-fixed behaving rodents, optimizing their applicability for experimental use. This approach will enable dynamic testing of the functional roles of arbitrary neurons and combinations of choice in behaving rodents. This project will develop and implement innovative optical methods for fine patterned stimulation of nervous systems and other excitable biological tissues. The approach will exploit current light-sensitive ion channels that can be inserted into neurons using the techniques of optogenetics. The planed optical illumination methods will, for the first time, allow fine spatial control and monitoring of brain activity. Further, these developments will provide new applications for high-resolution three-dimensional optical control of intra- and inter-cellullar signaling processes in any optically accessible tissue, greatly broaden their applicability in biological research and bioengineering. The project will result in broad distribution among interested scientists of all the methods developed. In addition, the results will be used to increase the awareness among the general public of the relevance of applied optics to daily life. These goals will be achieved through a concerted outreach program including optical imaging courses in Cold Spring Harbor Laboratory, volunteering internships, and lectures to local schools in Long Island and New York City.