DIFFERENTIAL, LONG-TERM, SYSTEMATIC SHIFTS AND RANDOM FLUCTUATIONS OF GRID, SPATIAL AND PLACE CELLS

The entorhinal-hippocampal circuit is crucial for spatial learning via synaptic plasticity. Consistently, hippocampal place cells and entorhinal grid cells show rapid, experience-dependent systematic changes, i.e. functional plasticity, on one-dimensional tracks. However, their long-term dynamics with repeated exposures to an environment, and its nature during unconstrained two-dimensional maze exploration, are unknown. Paradoxically, recent studies show long-term random drift, not systematic changes, of hippocampal place fields during random foraging. To address these mysteries, we measured the activity of many neurons in the medial entorhinal cortex (MEC) and from dorsal CA1, of freely behaving mice over one month using advanced calcium imaging. In addition to random-drift, grid and spatial cells' receptive fields showed long-term systematic shift, a phenomenon not previously reported. There were major differences in the long-term shifts of MEC grid and spatial cells –individual grid cells ratemaps changed by a small amount but the changes were coherent across the population, which is consistent with the attractor hypothesis; whereas simultaneously recorded individual spatial cells' ratemaps changed by a larger amount but the changes were not coherent across the population. As a result, the displacement of simultaneously recorded grid cells accumulated progressively over time. Further, CA1 place cells did not show any systematic shift. These results provide the first evidence of long-term functional plasticity of entorhinal grid and spatial cells in two dimensions. Although grid and spatial cells are anatomically intermixed, their differential dynamics suggests potential decoupling of these networks.