A Map-like Micro-Organization of Grid Cells in the Medial Entorhinal Cortex.

How the topography of neural circuits relates to their function remains unclear. Although topographic maps exist for sensory and motor variables, they are rarely observed for cognitive variables. Using calcium imaging during virtual navigation, we investigated the relationship between the anatomical organization and functional properties of grid cells, which represent a cognitive code for location during navigation. We found a substantial degree of grid cell micro-organization in mouse medial entorhinal cortex: grid cells and modules all clustered anatomically. Within a module, the layout of grid cells was a noisy two-dimensional lattice in which the anatomical distribution of grid cells largely matched their spatial tuning phases. This micro-arrangement of phases demonstrates the existence of a topographical map encoding a cognitive variable in rodents. It contributes to a foundation for evaluating circuit models of the grid cell network and is consistent with continuous attractor models as the mechanism of grid formation.

Membrane potential dynamics of grid cells.

During navigation, grid cells increase their spike rates in firing fields arranged on a markedly regular triangular lattice, whereas their spike timing is often modulated by theta oscillations. Oscillatory interference models of grid cells predict theta amplitude modulations of membrane potential during firing field traversals, whereas competing attractor network models predict slow depolarizing ramps. Here, using in vivo whole-cell recordings, we tested these models by directly measuring grid cell intracellular potentials in mice running along linear tracks in virtual reality. Grid cells had large and reproducible ramps of membrane potential depolarization that were the characteristic signature tightly correlated with firing fields. Grid cells also demonstrated intracellular theta oscillations that influenced their spike timing. However, the properties of theta amplitude modulations were not consistent with the view that they determine firing field locations. Our results support cellular and network mechanisms in which grid fields are produced by slow ramps, as in attractor models, whereas theta oscillations control spike timing.

Anomalous diffusion of single particles in cytoplasm.

The crowded intracellular environment poses a formidable challenge to experimental and theoretical analyses of intracellular transport mechanisms. Our measurements of single-particle trajectories in cytoplasm and their random-walk interpretations elucidate two of these mechanisms: molecular diffusion in crowded environments and cytoskeletal transport along microtubules. We employed acousto-optic deflector microscopy to map out the three-dimensional trajectories of microspheres migrating in the cytosolic fraction of a cellular extract. Classical Brownian motion (BM), continuous time random walk, and fractional BM were alternatively used to represent these trajectories. The comparison of the experimental and numerical data demonstrates that cytoskeletal transport along microtubules and diffusion in the cytosolic fraction exhibit anomalous (nonFickian) behavior and posses statistically distinct signatures. Among the three random-walk models used, continuous time random walk provides the best representation of diffusion, whereas microtubular transport is accurately modeled with fractional BM.