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Background

There are billions of neurons in the brain, forming neural circuits, in other words, computational units in order for animals to perform day-to-day tasks essential for their survival. In neuroscience research, to further the understanding of neural circuits, there is a need for new tools that can collect simultaneous measurements from large populations of neurons involved in a common neural computation and provide precise functional modulation. This way we can observe and manipulate the activities of neural circuits simultaneously. Neurons communicate with each other using action potentials and calcium influx can be used as an indicator for action potential activities, in other words, neuronal activities. Optical imaging in awake and free moving animals performing tasks expressing calcium indicators provides real-time functional and spatial information from individual neurons within local neural circuits. Spatial information is critical for our understanding of the neuronal activity because the brain is organized in a three-dimensional manner. The limitations of current imaging technology include small fields of view encompassing single brain regions and the requirement for head fixation (which prevents naturalistic behavior). In addition, most optical imaging systems do not allow for simultaneous high-resolution functional imaging in combination with spatially-localized optogenetic modulation. Simultaneous imaging and modulation enables close-loop modulation, which is an important tool for the study of neural circuits.

Technology

Researchers from the University of Colorado Boulder have developed a design for an optical device (‘3D-FAST’) that allows for rapid, real-time volumetric neural recording and precise optical stimulation. 3D-FAST will achieve unparalleled access to, and modulation of, neural circuitry in the cortex by pairing axial focusing capabilities using electrowetting technology with a miniature array of LED emitters and a high-resolution, high-speed detector. Due to its modular design, the 3D-FAST is scalable and customizable to meet experimental needs. This will achieve duplex recording of ~768,000 neurons and stimulation of ~60,000 neurons, with spatial resolution of 2.9 μm and 8 μm for recording and stimulation, respectively. These advances will allow single-neuron imaging combined with closed-loop modulation of cortical circuits, and creates the potential for future designs to include wireless, untethered imaging capabilities. Various embodiments of this technology provide for a miniature microscope for imaging and stimulating neural activity using light.

Benefits

• It includes a miniature electrowetting electrically tunable lens changes the focal length of the microscope, which allows three-dimensional imaging.
• It uses micro-structured LEDs for fluorescence illumination. A technique called Structured Illumination Microscopy whereby the optical scattering in tissue can be removed in post-processing, thus allowing clear images only at the focal plane of the microscope is proposed, for the first time, to be integrated into the technology.
• Another set of micro-structured LEDs for optogenetic stimulation is used in 3D-FAST. The LEDs are in a 10 x 10 grid and can illuminate regions of interest in the field of view of the microscope.
• The design is modular and can be stacked together for imaging/stimulation over larger brain areas or in larger animals.

Stage of Development

Technology Readiness Level (TRL): 4.

What's Next?

Looking for licensing opportunities.