Public-Private Partnerships

Project Summary Tinnitus or “ringing in the ears” is a hearing disorder that disproportionately impacts those who are or have served in the military. There is currently no effective cure for tinnitus. Patients with tinnitus exhibit broad changes in brain activity in the auditory system and elsewhere. One of the fundamental characteristics of tinnitus is a dysregulation in the excitatory/inhibitory balance in the central auditory system (CAS) leading to neuronal hyperexcitability and synchrony.

PROJECT SUMMARY A consensus has emerged in the Neurosciences over the last decade regarding the critical importance of understanding brain function at the level of neural circuits. Such an understanding can help us bridge across scales of investigation to provide a more comprehensive model of brain function, while also providing a more direct link to the dysfunctions associated with neurological disease.

Project Summary There is an enormous need for the development of a new class of neurotransmitter (NT) sensors that are versatile, selective, sensitive and reliable to allow investigation of the neurobiological mechanisms of behavior and disease symptoms. This

Abstract: Optogenetics can be used to selectively stimulate or suppress the firing of genetically targeted and spatially targeted mammalian neurons. It is used to study neuropsychiatric diseases in vivo with mouse models of conditions including epilepsy, schizophrenia, and Parkinson's. Optogenetics may be used as functional neurosurgical intervention for correcting disease states in the brain. It has been previously shown that seizures have the ability to be halted or reduced by optogenetic activation of inhibitory neurons with the use of Channelrhodopsin-2.

Project Summary Medical imaging technologies such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have been widely used in studying the underlying mechanisms of mental illnesses and neurological disorders such as brain tumors, Alzheimer’s disease, epilepsy, and depression, etc. However, PET and MRI scans are almost always ordered as separate studies on separate machines, often resulting in weeks of delay in acquiring critical information about a patient’s disease.

Over the past 15 years, new imaging technologies and methods for high throughput imaging have revolutionized structural biology by extending the resolution and scale of collected images in 3 dimensions. The resulting image volumes are more typically hundreds of GB to even tens of TB and in some cases approach PB sizes. These file sizes pose challenges for image acquisition, image analysis, and communication of a representative set of raw data and quantification. Image acquisition runs can be lengthy and expensive, and often errors are not identified until after the completion of scanning.

Project Summary: The main goal of this research project is to develop a new line of new stereotaxic devices for small animal research that outperforms existing devices in terms of accuracy, reproducibility, and ease of use. Advancing a tool such as an electrode, injection pipette or optical fiber through a small hole in the cranium, sometimes over long distances, and placing it precisely in a particular brain area, often much less than one millimeter in diameter, is a significant experimental challenge.

Boulder Nonlinear Systems (BNS) and Prof. Rikky Muller at UC-Berkeley propose a two-phase effort to address current speed limitations in holographic photostimulation. Specifically, the proposed innovations aim to achieve streaming of high-resolution holograms at up to 10,000 frames per second (fps) to enable closed-loop optogenetic control. Optical imaging and photostimulation have emerged as complimentary tools that allow not only direct imaging of neurons and their activity, but also the ability to directly stimulate or inhibit activity in living brains.

Abstract. Whole-organ 3D immunohistochemistry is revolutionizing the field of neuroscience, enabling unprecedented insight into the distribution of neural cells and neurological markers throughout the brain in health and disease.

Abstract This project describes the development of NeuroExM™, a highly innovative system for performing comprehensive spatial distribution analysis of populations of messenger RNAs (mRNAs) and proteins in tissue processed for expansion microscopy (ExM)). The groundbreaking technological advantage of ExM, which was recently developed by Dr. Edward S. Boyden (Dept. Biol. Engin., Media Lab and Dept. Brain Cognit. Sci., MIT, Cambridge, MA) and colleagues, is the ability to isotropically expand tissue and increase the size of the biological structures.