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Development of high-speed microscopes to study wide-scale neural activity

Periodic Reporting for period 1 - WideBrainImaging (Development of high-speed microscopes to study wide-scale neural activity)

Reporting period: 2016-03-01 to 2018-02-28

This Marie Curie fellowship was awarded at the beginning of March for a project that aimed to develop microscopes to image neural activity. Shortly after the project began the fellow was awarded an HFSP fellowship, and chose to relinquish the Marie Curie fellowship after only one month of activity. As such, limited progress was made under Marie Curie funding.

Understanding brain function is currently one of the highest priorities in science, with far-reaching implications across extremely diverse disciplines; ranging from fundamental questions of brain development, understanding and treatment of neurodegenerative diseases, through to human learning, and the development of machine learning algorithms. The immense complexity of brain structure and function means that in many cases state-of-the-art technology is inadequate, which has led to a major drive toward improved instruments to probe brain function. In particular, functional fluorescent imaging with genetically encoded calcium indicators has emerged as a powerful technology that allows single-neuron resolution of activity across large networks, thus opening a new regime of neuroscience research. These indicators necessitate new microscopes that can image across large brain volumes at high speeds.

The primary aim of this project is to develop microscopes for high-speed volumetric imaging of neural activity, and to then apply these to study outstanding questions in the function of the hippocampus.

The approach pursued here is to incorporate temporal focusing into scanning multiphoton microscopes to allow high speeds. Temporal focusing is a recently developed technique to controllably sculpt the excitation volume for multi-photon fluorescence, which we would use to expand the spot size controllably to reduce the number of pixels to be imaged within the volume; thereby increasing speed at the cost of resolution.
During the period of the Marie Curie funding, the fellow performed initial assessments of the planned microscope, including a literature search on related methods, some detailed calculations of the laser specifications required to reach the planned performance, and some preliminary feasibility tests.

The initial results appear promising, and construction of the microscope will continue under a different funding scheme.
Once completed the microscope is expected to allow ultrafast imaging of neural activity at depth exceeding the current state-of-the-art for fast imaging. This could have an important impact on neuroscience by enabling brain regions deep within the brain to be studied non-invasively. To date, however, progress is limited to preliminary assessments.