Synthetic imager to record cortical neural activity over whole cranium in freely-behaving animals

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Synthetic imager to record cortical neural activity over whole cranium in freely-behaving animals Understanding information flow across different brain regions during animal behavior is a key step to decipher how the brain works. It requires recording neural activities over a large neuronal population simultaneously, while maintaining a high spatiotemporal resolution. While fMRI can provide whole brain activity maps, it lacks both spatial and temporal resolutions. Conventional optical methods suffer from a tradeoff between the field of view and spatial resolution. Furthermore, majority of the imaging systems are bulky and the tested animals have to be set up in the head-fixed condition, which limits the behaviors that can be studied. In this proposal, we introduce a novel imaging modality which overcomes the above limits. We propose an integrated imager that can record neural activity on the whole cortical surface in freely-behaving mice. It leverages advanced microfabrication technologies, modern computational optics, and statistical deconvolution and demixing methods. The imaging system is a thin and flexible stack that consists of a microlens array layer, a programmable InGaN LED array layer and a photodetector array layer. It can be implanted conformally on the cortical surface of mice brain – as if it is a new skull, and record the neural activities over the cortex while the animal is freely behaving. The unique feature of the programmable LED array facilitates an accurate extraction of neuron locations and fluorescence background. Using computational optics and the modern demixing algorithm, the underlying neural activity can be extracted. Compared to the conventional optical microscopes, the proposed imaging system expands the field of view by two-orders of magnitude, while maintaining a good spatiotemporal resolution. This implantable imager will revolutionize the field of functional imaging and is applicable to many labs who are investigating cortical neural activity during animal behaviors. Furthermore, the proposed device is extendable to include photostimulation to manipulate neural activity over the whole cortical surface; it also serves as a prototype of wearable device to monitor brain activity of humans. The proposed device will enable a critical leap towards achieving the goals of the BRAIN initiative.