Imaging synaptic activity using super-resolution cannula microscopy

Summary

Principal Investigator: Rajesh Menon - Utah Neuroscience
Title: "Imaging synaptic activity deep in the brain using super-resolution cannula microscopy"
BRAIN Category: Neuroengineering and Brain-inspired concepts and design (#1532591)

This project will develop a tool for high-resolution (<100-nm) imaging of synapses in freely moving animals for neuronal studies. It will accomplish this goal by the development and integration of compact and lightweight cannula microscopy with in vitro fluorescence imaging with accompanying technology and methodologies for imaging synapses.

Principal Investigator: Rajesh Menon – Utah Neuroscience
Title: “Imaging synaptic activity deep in the brain using super-resolution cannula microscopy”
BRAIN Category: Neuroengineering and Brain-inspired concepts and design (#1532591)

Objective: This project will develop a tool for high-resolution (<100-nm) imaging of synapses in freely moving animals for neuronal studies. It will accomplish this goal by the development and integration of compact and lightweight cannula microscopy with in vitro fluorescence imaging with accompanying technology and methodologies for imaging synapses.

Image from University Utah Tech & Commercialization

Image from University Utah Tech & Commercialization

Abstract

Award Number#1533611

Objective: This project will develop a tool for high-resolution (<100-nm) imaging of synapses in freely moving animals for neuronal studies. It will accomplish this goal by the development and integration of compact and lightweight cannula microscopy with in vitro fluorescence imaging with accompanying technology and methodologies for imaging synapses.

Non-Technical

The long-term vision of this project is to image with high resolution deep inside the brain of freely moving mice using inexpensive technologies so as to elucidate the fundamental basis of information processing and memory. Changes in synaptic strength at specific synapses are thought to underlie memory encoding and storage, yet there is very little experimental evidence for this theory in the intact brain due to technical limitations of visualizing the specific synaptic pattern involved in experience-dependent learning. This project aims to overcome this limitation by transforming a simple, inexpensive cannula into a super-resolution fluorescence microscope. Commercialization of this technology will be pursued after the fundamental science and engineering has been demonstrated for widespread dissemination.

Technical:

The objective of this proposal is to image neuronal activity, neuron structure and protein localization deep in the brain with sub-100nm resolution using computational cannula microscopy (CM) and novel molecular reporters of synaptic activity. CM will allow imaging of the brain in awake, freely moving animals at unprecedented spatial resolution. Current techniques in freely moving animals are limited to imaging the brain near the surface, include large and heavy head stages with moving parts, and cannot penetrate deep into the brain without significant damage to surrounding tissue. The ultimate goal of this proposal is to allow imaging of individual synapses in freely moving animals. We have already developed the framework for in vitro fluorescence imaging using CM. During this project, we will extend CM to enable: (1) super-resolution (< 100nm resolution) fluorescence microscopy and (2) deep-brain imaging (depth > 1mm) with the vision of imaging activity and protein localization in individual synapses in the deep brain of freely moving animals. Changes in the strength of individual synapses are thought to underlie learning and memory in the brain, yet this fundamental theory of brain function lacks tangible experimental evidence to support it in vivo. Our project will enable studies that address the causal role of molecular events at individual synapses in mediating behavior and information processing.

NSF Project Information

NSF webpage: nsf.gov/awardsearch/showAward?AWD_ID=1533611

NSF Org: ECCS   Div Of Electrical, Commun & Cyber Sys

Start Date:  September 1, 2015      End Date: August 31, 2019 (Estimated)

Awarded Amount to Date: $920,000.00

Investigator(s): Rajesh Menon rmenon@eng.utah.edu (Principal Investigator)
Erik Jorgensen (Co-Principal Investigator)
Jason Shepherd (Co-Principal Investigator

NSF Program(s): EFRI RESEARCH PROJECTS, – IntgStrat Undst Neurl&Cogn Sys

Program Reference Code(s): 004E, 8089, 8091, 8551

Sponsor: University of Utah
75 S 2000 E
SALT LAKE CITY, UT 84112-8930

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