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. When performed through multiphoton microscopes equipped with phase-shaping SLMs, neuroscientists can now simultaneously control user-defined populations of neurons distributed across different cortical layers in awake and behaving animals. This is accomplished through digital holography, in which the SLM produces a three-dimensional light field in the sample (i.e., brain) with foci of light targeted directly to neurons of interest. Stimulation of specifically targeted groups of neurons more accurately mimics natural neural dynamics, in which neuronal ensembles are believed to be critical to encoding information. As a result, this holographic photostimulation approach is yielding novel insights into the neural processes behind perception and learning that could not be gained through alternative means. Increasingly, neuroscientists wish to use this technique in closed-loop experimental protocols. In these protocols, the neural or behavioral activity of the animal would dictate the holographically targeted neurons, which in turn would further alter the activity in a real-time feedback loop. To realize this goal, neuroscientists require the computer-to-hologram pipeline to be accelerated well beyond 1,000 frames per second (fps) (≤ 1 ms response time). The fastest commercial SLMs, developed by Boulder Nonlinear Systems (BNS), can achieve up to 500 fps in holographic photostimulation applications. Although these systems use a high-speed data pipeline capable of transmitting phase masks to the SLM at several kilohertz, these systems are limited by the liquid crystal used to modulate the phase of the light and are thus too slow for the envisioned closed-loop protocols. Meanwhile, piston-type microelectromechanical system (MEMS) mirrors, developed by Prof. Rikky Muller’s lab at UC-Berkeley, are capable of pixelated phase modulation at speeds on the order of 10 kHz. Translation of this approach into the high-resolution modulators required for holography requires an application-specific integrated circuit (ASIC) capable of addressing many independent pixels with analog voltages > 10 V and a data pipeline to transfer data at the speeds of the MEMS. In this two-phase effort, BNS and Prof. Rikky Muller at UC-Berkeley will remove these critical barriers by using the commercial BNS SLM backplanes as the MEMS ASIC and using the BNS drive electronics to achieve computer-to-hologram rates up to 10 kHz. In Phase I, we will rigorously characterize the compatibility of the Muller Labs’ MEMS pixels with the BNS backplane and drive scheme using a 64×64 resolution MEMS array driven by a BNS 768×768 backplane assembled together on a host printed circuit board (PCB). This architecture enables thorough and independent characterization of MEMS and backplane behaviors while being sufficient to demonstrate the high-speed holography used in photostimulation protocols. This Phase I proof-of-concept MEMS SLM will have a maximum speed of 2.5 kHz, which is already a 5× improvement over the state-of-the-art. In Phase II, we will directly integrate the MEMS array onto the BNS backplane, targeting up to a 512×512 MEMS SLM capable of up to 10 kHz frame rates, and demonstrate in vivo photostimulation at kHz speeds. In addition, this MEMS SLM has strong applications in laser communications, atmospheric sensing, and AR/VR near-eye display.

There is an optical revolution underway in neuroscience that is providing researchers with new tools to both record and control neural activity with light at the cellular level. Spatial light modulators (SLMs) are amongst the most powerful of these tools, in that they enable neuroscientists to holographically target neural stimulation or inhibition of 3D populations of cells in vivo. We propose a new SLM that marries the kilohertz speeds of microelectromechanical systems (MEMS) with proven commercial SLM drive techniques and architectures to enable a new paradigm of high-speed neural interrogation and better understand the inner workings of the brain.