TY - JOUR TI - A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging AU - Sofroniew, Nicholas James AU - Flickinger, Daniel AU - King, Jonathan AU - Svoboda, Karel A2 - Rieke, Fred VL - 5 PY - 2016 DA - 2016/06/14 SP - e14472 C1 - eLife 2016;5:e14472 DO - 10.7554/eLife.14472 UR - https://doi.org/10.7554/eLife.14472 AB - Imaging is used to map activity across populations of neurons. Microscopes with cellular resolution have small (<1 millimeter) fields of view and cannot simultaneously image activity distributed across multiple brain areas. Typical large field of view microscopes do not resolve single cells, especially in the axial dimension. We developed a 2-photon random access mesoscope (2p-RAM) that allows high-resolution imaging anywhere within a volume spanning multiple brain areas (∅ 5 mm x 1 mm cylinder). 2p-RAM resolution is near diffraction limited (lateral, 0.66 μm, axial 4.09 μm at the center; excitation wavelength = 970 nm; numerical aperture = 0.6) over a large range of excitation wavelengths. A fast three-dimensional scanning system allows efficient sampling of neural activity in arbitrary regions of interest across the entire imaging volume. We illustrate the use of the 2p-RAM by imaging neural activity in multiple, non-contiguous brain areas in transgenic mice expressing protein calcium sensors. KW - calcium KW - 2-photon KW - two-photon KW - barrel cortex KW - dendritic spines KW - neural coding JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -