While the Neuropixels probes increase cell numbers by an order of magnitude, their spatial resolution is as limited as in conventional tetrode-based extracellular recordings:
Optical imaging provides a complementary solution to neurophysiological recordings, with high spatial but poorer temporal resolution. The technique uses an indicator molecule such as fluorescent GCaMP6 to monitor changes in intracellular free calcium concentrations optically across wide fields of view (FOV), allowing many hundreds of individual neurons to be followed at near-spike temporal resolution. High spatial resolution has been obtained with two-photon (2P) microscopy but until now this technology was limited to stationary table-top setups, where the animal must be head-fixed under the objective. Recently, using a hollow-core photonic crystal fiber to deliver 920-nm femtosecond laser pulses, Zong et al. (2017; PMID: 28553965) developed a portable light-weight (2-g) 2P microscope. The miniature microscope was able to image biosensors such as GCaMP6 at impressive cellular and subcellular resolution in freely moving mice.