Advances in point spread function engineering for functional imaging of neural circuits in vivo

Simultaneous recording of large-scale neural network activity in vivo is essential for unraveling fundamental processing mechanisms in the brain. For such applications, optical imaging becomes indispensable because it is minimally-invasive, allows flexible recording characteristics, and provides high signal-to-noise ratio. However, physical limitations hinder the pursuit of increasing the imaging scale, speed, and penetration depth for increasing this method’s applicability for the growing field of neuroscience. In this review, we first summarize the practical requirements and limitations in current functional imaging systems, followed by a review of the latest hardware developments to supercede current limitations, specifically for the widely adopted multiphoton microscopy. We then introduce advances in point-spread-function (PSF) engineering, i.e. the manipulation of the microscope’s PSF, and discuss the possibility of integrating computational approaches together with PSF engineering to further enhance performance. We expect that future integration of computational imaging and advanced optical methods will be adopted to meet the emerging requirements of modern neuroscience.