Project Summary A multi-scale, mechanistic understanding of neural circuits that includes both local- and whole-brain interconnections still remains elusive. One of the fundamental challenges is the lack of tools for monitoring, with high spatiotemporal resolution, the activity of local neuron ensembles simultaneously in different regions of the brain in awake, freely-behaving animals. This calls for the design of ultrahigh density neural probes capable of recording from thousands of neurons with high spatiotemporal resolution. While there has been tremendous progress on the design of conventional passive and active electronic neural probes, these technologies are reaching scaling limits. We need to break away from the conventional scheme of recording and relaying electrical neural signals using passive or active electronic neural probes to enable breakthrough improvements in the number of simultaneous channels that we can record from the brain. Here, we propose a disruptive approach based on fundamental advancements in optics and microelectromechanical systems (MEMS) to deliver an innovative opto-mechanical probe that can potentially have more than a couple of thousand simultaneously active recording electrodes in the same footprint of a conventional passive probe. All of the recorded neural signals in our design are encoded in the optics domain to leverage the ultrahigh bandwidth of light for communicating the recorded aggregate neural signals to outside the brain on a single optical waveguide. In this scheme, each recording channel is encoded onto a single wavelength of light that travels along the same waveguide. This wavelength domain multiplexing (WDM) method enables a true simultaneous recording of many channels, unlike the time domain multiplexing (TDM) scheme that is used in active electronic neural probes, which relies on sequential recording of multiple channels. Therefore, our design enables massive scaling of the number of simultaneously recorded channels, while enhancing SNR, preserving the bandwidth, and minimizing adverse effects of active electronic neural probes such as heat generation inside the brain. The core unit cell of our neural probe is an electromechanical sensor that detects electrical neural signals and converts them to small mechanical motions of a membrane, which in turn modulates a photonic microresonator. Therefore, the electrical neural signal is transformed to a mechanical and then an optical signal. The ultra-high quality factor optical microresonator enhances the detected signals. A single common waveguide coupled to multiple microresonators carries the optical signals to the backend outside the brain. This novel design enables massive scaling of the number of recording channels without increasing the size of the neural probe. Moreover, the conversion of electrical signals to optical signals results in enhanced signal-to-noise ratio (SNR) and also makes the transmitted signals immune to unwanted electrical interference. After successful demonstration of multiplexed electro-opto-mechanic neural recording in this project, the results can be extended in future efforts to i) develop even much higher density neural probes with more than 1000 channels and ii) demonstrate its in vivo application.

Public Narrative Designing new therapeutics to treat neural disorders such as Parkinson's disease or epilepsy require understanding the underlying neural circuits function in health and disease. Here, we propose to develop and test novel optomechanic neural implants for simultaneous electrical recording from many independent channels, for the first time, which enables large-scale network investigation with high spatiotemporal resolution. Such an instrument will significantly advance our understanding of brain function and dysfunction in animal models, which can be quickly translated to humans to detect the onset of disease states and design proper interventions.