Sofroniew, N.J. et al. Elife 5, e14472 (2016).

A traditional trade-off of large-field-of-view microscopes is their low resolution, especially in the axial direction. Sofroniew et al. have now developed a microscope that is not afflicted by this trade-off. Their two-photon random access mesoscope has a field of view that covers several brain regions, lateral resolution that is close to the diffraction limit and axial resolution that is below the size of neuronal cell bodies. This enables the visualization of more than 200,000 neurons in the mouse brain at subcellular resolution. Furthermore, the researchers were able to image the activity of thousands of neurons in behaving animals sufficiently fast to discern action potentials and to correlate the activity of single neurons with the activity of whole brain areas.