WideBrainImaging · Development of high-speed microscopes to study wide-scale neural activity
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-03-01 → 2018-02-28
- EU contribution
- €178,157
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Development of high-speed microscopes to study wide-scale neural activity
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.
Data: CORDIS, © European Union
Project objective
The dynamic of neural computation is often studied in individual cells using inserted electrodes, or using low-resolution methods such as EEG. Functional fluorescent imaging has recently emerged as a powerful complementary tool that allows single-cell resolution of relatively large networks, opening a new regime to neuroscience. However, complex brains are generally opaque and can only be studied with scanning two-photon microscopes; with the achievable depth limited to ~0.6mm, and the volume limited by the relatively slow scan.This project will develop ultrafast scanning multiphoton microscopes to image neural activity at cellular resolution over large volumes, and at greater depth. Using these we will study patterns of activity in the hippocampus, and particularly attempt to observe the pathways involved in memory retention. To increase speed we will use temporal focusing to controllably sculpt the excitation volume and enlarge the focal spot. This reduces the number of measured pixels and allows faster scanning (or larger volume), at the cost of resolution. This will allow 25x faster imaging in a resonant scanning two-photon microscope; allowing observation of many thousands of cells at once, which could reveal the wide-scale characteristic activity.We will build a second microscope that uses three-photon excitation with temporal focusing. Three-photon imaging relies on longer wavelengths that penetrate deeper into tissue, and also suppresses background fluorescence which could otherwise limit depth. Consequently, this microscope will allow high-speed imaging at depth exceeding 1mm. This allows study of information transfer across multiple layers; or provides access to the hippocampus through the intact cortex. These studies could provide crucial insights to neuroscience that are currently accessible only for a few neurons.Following completion of this project these microscopes could have an enduring impact as they continue to be used to study neural dynamics.
Original text from CORDIS.
Participants
- FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH · WienCoordinatorAustria
Links
Data: CORDIS, © European Union