The Functional Micro-organization of Grid Cells Revealed by Cellular-Resolution Imaging

Abstract

Summary Establishing how grid cells are anatomically arranged, on a microscopic scale, in relation to their firing patterns in the environment would facilitate a greater micro-circuit level understanding of the brain’s representation of space. However, all previous grid cell recordings used electrode techniques that provide limited descriptions of fine-scale organization. We therefore developed a technique for cellular-resolution functional imaging of medial entorhinal cortex (MEC) neurons in mice navigating a virtual linear track, enabling a new experimental approach to study MEC. Using these methods, we show that grid cells are physically clustered in MEC compared to non-grid cells. Additionally, we demonstrate that grid cells are functionally micro-organized: The similarity between the environment firing locations of grid cell pairs varies as a function of the distance between them according to a “Mexican Hat” shaped profile. This suggests that, on average, nearby grid cells have more similar spatial firing phases than those further apart.

Micro-, Meso- and Macro-Dynamics of the Brain

“…Cell pairs <35 μm apart, displayed a significant correlation but not separable from correlations from common neuropil or activity bleed-over in the imaging technique (Dombeck et al 2010). Imaging of grid cells using similar methods has recently confirmed that grid phase is organized non-topographically at the macroscopic level, but larger-than-expected correlations were reported for cells that were nearest neighbors (Heys et al 2014).…”

“…It should be kept in mind, however, that the identification of explicit representations with linearly separable ones is a working hypothesis that remains under-investigated. More generally, it is particularly difficult to determine whether and how brain responses play a causal role in behavior and subjective perception (see, e.g., Rangarajan et al 2014). Beyond decoding analyses, this ambiguity is in fact intrinsic to any non-causal brain-behavior correlation method.…”

Spatial representation in the hippocampal formation: a history

“…Might such connectivity between clonally related cells underlie a possible preferential coupling between MEC cells with similar spatial or directional tuning, in the same way that cells from the same clone exhibit similarities in orientation preferences (and possibly preferential coupling) in the visual cortex 268,269 ? Does the young MEC have a topographically arranged teaching layer, with connections between clonally related cells, that during early postnatal development gives way to the largely nontopographical 9,270 grid cell network of the adult MEC (Fig. 8 of ref. 91)?…”

How Animals Find Their Way in Space. Experiments and Modeling

“…Последнее подразумевает, что функция корреляции между импульсной активностью двух клеток решетки в зависимости от физического расстояния между этими нейронами имеет форму мексиканской шляпы, т.е. нейроны, расположенные рядом, разряжаются в одинаковые моменты времени, а импульсные последовательности нейронов, расположенных на среднем расстоянии, анти-коррелированы [31,49].…”

“…При введении в модель дополнений, например, ритмического входа [75], можно получить эффект фазовой прецессии, однако в чем заключается роль этого явления, модель не описывает. С другой стороны, в последнее время аттракторные модели получили значительную поддержку в виде работ, показывающих пространственную и функциональную кластеризацию нейронов энторинальной коры [31,49].…”