The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in cortical microcircuits is poorly understood. Here we show that the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the 'grid cell', which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.
The hippocampal formation can encode relative spatial location, without reference to external cues, by the integration of linear and angular self-motion (path integration). Theoretical studies, in conjunction with recent empirical discoveries, suggest that the medial entorhinal cortex (MEC) might perform some of the essential underlying computations by means of a unique, periodic synaptic matrix that could be self-organized in early development through a simple, symmetry-breaking operation. The scale at which space is represented increases systematically along the dorsoventral axis in both the hippocampus and the MEC, apparently because of systematic variation in the gain of a movement-speed signal. Convergence of spatially periodic input at multiple scales, from so-called grid cells in the entorhinal cortex, might result in non-periodic spatial firing patterns (place fields) in the hippocampus.
Theoretical models have long pointed to the dentate gyrus as a possible source of neuronal pattern separation. In agreement with predictions from these models, we show that minimal changes in the shape of the environment in which rats are exploring can substantially alter correlated activity patterns among place-modulated granule cells in the dentate gyrus. When the environments are made more different, new cell populations are recruited in CA3 but not in the dentate gyrus. These results imply a dual mechanism for pattern separation in which signals from the entorhinal cortex can be decorrelated both by changes in coincidence patterns in the dentate gyrus and by recruitment of nonoverlapping cell assemblies in CA3.
perience correlate with subsequent choices offers strong evidence for the existence of intrinsic preferences. Although it is not clear how malleable these preferences are, their existence may have health implications for the way in which individuals deal with events that are known to be unpleasant-for example, going to the doctor for painful procedures. The neurobiological mechanisms governing dreading behavior may hold clues for both better pain management and improvements in public health.
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