Cooperative Agreements

Modular systems for measuring and manipulating brain activity

 DESCRIPTION (provided by applicant): The brain is a massively interconnected network of specialized circuits. Even primary sensory areas, once thought to support relatively simple, feed-forward processing, are now known to be parts of complex feedback circuits. All brain functions depend on millisecond timescale interactions across these brain networks, but current approaches cannot measure or manipulate these interactions with sufficient resolution to resolve them.

Time-Reversal Optical Focusing for Noninvasive Optogenetics

 DESCRIPTION (provided by applicant): Our bodies appear optically opaque because biological tissue scatters light strongly. Although advances such as multiphoton excitation have enabled deeper access for optical imaging by gating out scattered light, these strategies are still fundamentally limited to superficial depths (~ 1 mm). Yang's group at Caltech has pioneered time-reversal symmetry of optical scattering as a direct strategy to 'turn off' tissue scattering.

FAST HIGH-RESOLUTION DEEP PHOTOACOUSTIC TOMOGRAPHY OF ACTION POTENTIALS IN BRAINS

 DESCRIPTION (provided by applicant): Revealing how our brain works is a great challenge but yet worth our every effort: it will not only illuminate the profound mysteries in science but also provide the key to understanding and treating neurological diseases such as Alzheimer's and Parkinson's. The objective of the proposed three-year research is to develop a high- speed, high-spatial-resolution, deep-penetration photoacoustic computed tomography (PACT) system for real- time imaging of action potentials in mouse brains.

Genetically encoded reporters of integrated neural activity for functional mapping of neural circuitry

 DESCRIPTION (provided by applicant): One of the major challenges in neuroscience is to link the structure to the function of neural circuits. To achieve this goal, we need to understand the connectivity between defined neuronal populations and the contribution of these neurons to physiological processes, behavioral responses and disease states. Recent advances in imaging techniques allow us to visualize the brain structure with cellular resolution.

Optogenetic mapping of synaptic activity and control of intracellular signaling

 DESCRIPTION (provided by applicant): This proposal aims to develop new molecular techniques to map activities of neurons, manipulate the strength of communication between neurons and disrupt intracellular signaling. These 'optogenetic' approaches will be used to further our understandings of brain function on behavior and have important implications in our understandings of neurological conditions and neurodegenerative diseases.

Modular nanophotonic probes for dense neural recording at single-cell resolution

DESCRIPTION (provided by applicant): Our understanding of the properties of individual neurons and their role in brain computations has advanced significantly during the last few decades. However, we are still very far from understanding how large assemblies of cells interact to process information. Electrophysiology is the gold standard with unmatched temporal resolution, but is currently limited in terms of its ability record from every single neuron withina volume with cell-type specificity.

Genetically encoded sensors for the biogenic amines: watching neuromodulation in action

 DESCRIPTION (provided by applicant): The goal of this proposal is to develop a toolbox of genetically encoded indicators for biogenic amines, the most important family of neuromodulators. All nervous systems are subject to neuromodulation, which reconfigure the dynamics of neural circuitry by transforming the intrinsic firing properties of targeted neurons and regulating their synaptic plasticity. The altered dynamics of the neuromodulators have been implicated in a number of human neurological and psychiatric diseases, including Parkinson's, schizophrenia and addiction.

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