Skytoen, E. R. | Search bioRxiv

bioRxiv2021

Large-scale two-photon calcium imaging in freely moving mice

We developed a miniaturized two-photon microscope (MINI2P) for fast, high-resolution, multiplane calcium imaging of over 1,000 neurons at a time in freely moving mice. With a microscope weight below 3g and a highly flexible connection cable, MINI2P allowed imaging to proceed with no impediment of behavior in half-hour free-foraging trials compared to untethered, unimplanted animals. The improved cell yield was achieved through a new optical system design featuring an enlarged field of view (FOV) and a new micro-tunable lens with increased z-scanning range and speed that allowed for fast and stable imaging of multiple, interleaved planes as well as 3D functional imaging. A novel technique for successive imaging across multiple, adjacent FOVs enabled recordings from more than 10,000 neurons in the same animal. Large-scale proof-of-principle data were obtained from cell populations in visual cortex, medial entorhinal cortex, and hippocampus, revealing spatial tuning of cells in all areas, including visual cortex. HighlightsWe developed a lightweight 2-photon miniscope for imaging in freely-foraging mice Activity can be monitored in volumes of over 1,000 visual or entorhinal-cortex cells A new z-scanning module allows fast imaging across multiple interleaved planes Successive imaging from adjacent regions enables imaging from more than 10,000 cells

neuroscience↗

bioRxiv2018

Object-vector coding in the medial entorhinal cortex

Mammals use distances and directions from local objects to calculate trajectories during navigation but how such vectorial operations are implemented in neural representations of space has not been determined. Here we show in freely moving mice that a population of neurons in the medial entorhinal cortex (MEC) responds specifically when the animal is at a given distance and direction from a spatially confined object. These object-vector cells are tuned similarly to a spectrum of discrete objects, irrespective of their location in the test arena. The vector relationships are expressed from the outset in novel environments with novel objects. Object-vector cells are distinct from grid cells, which use a distal reference frame, but the cells exhibit some mixed selectivity with head-direction and border cells. Collectively, these observations show that object locations are integrated in metric representations of self-location, with specific subsets of MEC neurons encoding vector relationships to individual objects.

neuroscience↗