A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging

By Nicholas J. Sofroniew, Daniel Flickinger, Jonathan King, Karel Svoboda. 2016

593 citations recorded by the source corpus.

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 (Ø 5 mm × 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 threedimensional 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.

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Citations in the corpus

Re-evaluating circuit mechanisms underlying pattern separation (2019, neutral): “Several promising new imaging technologies that can record intracellular calcium from large numbers of identified cells have also been recently developed (Grewe et al., 2011; Katona et al., 2012; Froudarakis et al., 2014; Nadella et al., 2016; Sofroniew et al., 2016; Yang et al., 2016).”
Fully Integrated Silicon Probes for High-Density Recording of Neural Activity (2017, unknown): “We further sought to develop probes with (3) low noise, (4) resistance to movement artefacts or other interference, and (5) efficient data transmission by integrating low noise analogue amplifiers, multiplexers and digitizers into the probe base.”
Suite2p: beyond 10,000 neurons with standard two-photon microscopy (2016, methodology): “First, it should be fast, to keep up with ever-larger data sets produced by next-generation microscopes 1,2 .”
Tracking the Same Neurons across Multiple Days in Ca2+ Imaging Data (2017, methodology): “The registration procedure is fully automated and does not require manual inspection of each cell, making it scalable for very large FOVs (Kim et al., 2016; Pachitariu et al., 2016; Sofroniew et al., 2016).”
Engineering a Less Artificial Intelligence. (2019, background): “…and behavioral neuroscience studies suggest that the ability to generalize categories and rules to novel situations and stimuli is also pre-sent in many other animals, including rodents (Murphy et al., 2008), birds (Vaughan, 1988; Soto and Wasserman, 2014), and monkeys (Minamimoto et al., 2010).”