Cooperative Agreements

Two-photon laser scanning microscopy powers many projects in the.

Recombinant Immunolabels for Nanoprecise Brain Mapping Across Scales Understanding brain function and dysfunction requires an understanding of the circuitry of the brain from molecules to cells to circuits. While no single technique can achieve this, a strategic combination of techniques applied across scales can provide information that when integrated can lead to a more complete picture.

Understanding the function of the nervous system requires a sophisticated understanding of its main output, behavior. Although our ability to record from and to manipulate neurons and neural circuits has accelerated at a spectacular pace over the last decade, progress has lagged in coupling the interrogation of the nervous system to similarly high-resolution measures of behavior.

Project Summary Blindness in the United States is a large and increasing problem. Any significant vision loss is debilitating, but profound blindness is devastating to an individual’s ability to be independent and to perform everyday tasks and activities. Hundreds of thousands of people in the United States suffer from profound blindness, and most of these currently have no hope of vision recovery. Recently, a retinal prosthesis has become available in Europe, U.S., and Canada for people with profound vision loss from Retinitis Pigmentosa, a degenerative retinal disease.

PROJECT SUMMARY / ABSTRACT Recent advances in design and actuation have led to important improvements in prosthetic limbs. However, these devices lack a means for providing direct sensory feedback, requiring users to infer information about limb state from pressure on the residual limb. Lack of sensation limits their ability to control the prosthesis and leads to slow gait and increased risk of falling. There is also evidence that lack of sensory feedback contributes to phantom limb pain (PLP), and that electrical stimulation at the dorsal root ganglia (DRG) can reduce PLP.

Abstract DBS therapy for Parkinson's disease is now the primary surgical approach for Parkinson's disease, recently FDA approved at 4 years after onset of disease. However, this therapy is still limited to treatment of a subset of motor symptoms (ie, tremor, rigidity, bradykinesia and dyskinesias) and requires considerable postoperative clinical adjustment to program and maintain function. A number of improvements to DBS for PD are being tested, including changes in patterns of stimulation and specific targets.

Recording the electrical impulses of many individual neurons in intact brain circuits in real time would enable a detailed understanding of how the brain processes information. Technologies for high-fidelity large-scale voltage sensing with cellular resolution would also provide new high-resolution methods for analyzing for how diseases of the brain impact circuit function. However, current methods lack the ability to detect the rich variety of electrical impulses in large numbers of neurons in deep locations in the brain.

We propose to design, build, apply, and disseminate a device that will push the boundaries of current technology for volumetric imaging of distributed activity of large-scale neuronal circuits at high neuronal sampling rate and single cell resolution. The proposed technology will enable unbiased Ca2+ imaging of unprecedentedly large cortex-wide volumetric fields of views (V-FOV) of ~5x5x0.8mm at multi-Hertz time resolution in behaving rodents and marmosets.

Vertebrate behaviors emerge from interactions of neurons across the brain, but the tools for revealing neuronal structure and function at the cellular level in living animals access only small portions of the brain. We must move toward access to structure and function anywhere in the brain of individual adult, behaving animals. In vivo three photon (3P) microscopy, a recent, but proven, technology allows optical access to deeper structures than ever before in intact mammalian brains, but much optimization remains to catalyze its wider adoption.

ABSTRACT The public health burden of Treatment Resistant Depression (TRD) has prompted clinical trials of deep brain stimulation (DBS) that have, unfortunately, produced inconsistent outcomes. Potential gaps and opportunities include a need: (1) to better understand the neurocircuitry of the disease; (2) for precision DBS devices that can target brain networks in a clinically and physiologically validated manner; and (3) for greater insight into stimulation dose-response relationships.