Grant: Collaborative Health Research Projects

To break the mysteries of the normal and diseased brain we must be able to visualize the very complex circuitry of the brainwith high resolution (thousandths of millimeters). This can be achieved with light microscopy which offers high resolution butalso the ability to visualize wide areas at once. Yet, imaging the entire brain with light is a major challenge because the brainis relatively opaque to light (because it scatters light this is why it tends to look white when one looks at it). Recentbreakthrough technologies are able to render animal and human brain samples virtually transparent opening the door toimaging entire brains at once. The challenge remains of building a microscope capable of doing this. The proposal builds ona recent technology we have developed using a novel type of lens called axicons, which generates extreme long lines oflight that can traverse the entire brain and enable its visualization from the side. Producing light lines with sufficient energyremains challenging. We have a solution with the use of novel powerful lasers called regenerative-amplifier pulsed lasers.The combination of these technologies will allow us to develop, for the first time, a type of microscope capable of generatinghigh resolution, large scale images of entire brain areas (centimeter-wide regions). This technology promises to transformour ability to understand the neuro-circuitry of the brain and thus significantly advance understanding of neurological andpsychiatric diseases which involve remodeling of brain connections.