? DESCRIPTION (provided by applicant): Improving our understanding of the fundamental circuitry and dynamics of the brain has far reaching implications for a wide range of fields, including mental health, computing, and the philosophy of the mind. To this end, one of the critical questions currently facing neuroscientists lies in how brain states and behaviors arise from the activity of ensembles of neurons. Currently, efforts to answer this question are hampered in part by the disconnect between the sub-millimeter length scales accessible to the optical techniques used to probe cellular- level dynamics and the millimeter-scale resolution available to the whole brain imaging techniques used to monitor brain states. Boulder Nonlinear Systems (BNS) and Prof. Edward Boyden's Synthetic Neurobiology Group at the Massachusetts Institute of Technology (MIT) Media Lab propose a novel two-phase design effort to overcome this imaging gap to improve functional mapping of brain networks. The critical barrier to increasing the field of view (FOV) and speed in many cutting-edge optical techniques is the spatial light modulator (SLM), which enables the generation of many independent beamlets capable of activating and recording neural activity simultaneously across ensembles of neurons in three dimensions. Phase I will address this barrier by developing and deploying new modeling capabilities, which will then be available to the optical design community, to determine the SLM specifications and optical system required to provide a 1×1×0.5 mm3 FOV and 1 ms switching speed in a practical holographic multiphoton microscope. These capabilities will increase the accessible volume of brain tissue by more than an order of magnitude in comparison with the current literature while reducing the SLM response time down to the level of single neuron firing events (action potentials). In Phase II, BNS and MIT will develop the new next-generation SLM and evaluate it in functional neural mapping experiments. The impact of this project will be multifold: we will develop new modeling capabilities to enable optical designers and researchers to properly simulate SLM-based optical systems for the first time, and we will use this holistic modeling approach to develop a new SLM device with vastly superior performance than anything on the current market. This next-generation SLM is predicted to have a powerful impact in the field of neuroscience and find a wide commercial market across many disciplines.