A major technical hurdle to revealing the principles that brains use in order to produce behavior is the ability to monitor structure and function with single cell and subcellular resolution throughout the nervous system — a necessity because behavior emerges from broad interactions of neurons across brains, even in the simplest organisms. This team of investigators will push optical microscopy to this goal through the development of a Laboratory for Innovative Neurotechnology at Cornell (LINC). Experts from physics, engineering and biology will work together to develop a suite of optical imaging tools that will overcome current barriers in the depth, breath and speed of imaging to enable the structure and activity of neurons throughout living brains of intact animals across a range of species to be mapped during the execution of complex behaviors, and then disseminate this technology to the broader neuroscience community.

Key Research Resources Being Developed and Disseminated

The hub aims to overcome three barriers faced by neuroscientists:
Deep imaging of intact brains – Multiphoton microscopy, invented at Cornell, has allowed neuroscientists to record the activities of individual neurons up to approximately 1 millimeter deep into a mouse brain. However, the mouse brain is about 8 millimeters thick, and even thicker in larger animals. The hub will optimize a recently developed three-photon microscope and focus on making the tool widely available.
Imaging of large and multiple neural regions – The best whole nervous system images have come from larval zebrafish, but existing imaging tools cannot holistically view larger brains, even at the scale of an adult zebrafish. Using a combination of two- and three-photon microscopy, the hub will develop a new tool to simultaneously observe neurons in different regions of the mouse brain and the spinal cord.
Faster imaging for volumetric recording – To record large numbers of neurons, high-speed imaging will be achieved through the development of an adaptive illumination microscope in which the sample becomes an integral part of the imaging system. By leveraging prior knowledge of the sample, optimum laser exposure will be used to record the activities from a large number of neurons.

The goal of the Cornell NeuroNex Technology Hub is to rapidly introduce technology advancements to the neuroscience community. The new Laboratory for Innovative Neurotechnology at Cornell (LINC) will be open to visits by outside researchers, who can see firsthand the latest developments in deep brain imaging. NeuroNex faculty will present findings at conferences and workshops, such as Cold Spring Harbor Laboratory and Woods Hole Neural Systems and Behavior courses. The broader research community will be invited to participate in annual Cornell NeuroNex conferences/workshops. These will be designed as multi-day events with presentations by invited speakers, a poster session, a vendor-supported technical session in which participants can observe working instrumentation and learn more about specific techniques.