Grid cell firing patterns signal environmental novelty by expansion

Abstract

The hippocampal formation plays key roles in representing an animal's location and in detecting environmental novelty to create or update those representations. However, the mechanisms behind this latter function are unclear. Here, we show that environmental novelty causes the spatial firing patterns of grid cells to expand in scale and reduce in regularity, reverting to their familiar scale as the environment becomes familiar. Simultaneously recorded place cell firing fields remapped and showed a smaller, temporary expansion. Grid expansion provides a potential mechanism for novelty signaling and may enhance the formation of new hippocampal representations, whereas the subsequent slow reduction in scale provides a potential familiarity signal.single unit | spatial memory | hippocampus G rid cells in the medial entorhinal cortex (mEC) of freely moving rodents exhibit a striking triangular grid-like firing pattern (1). Although the grid patterns are anchored to familiar environmental cues (1, 2), their maintenance in darkness and across different environments (1, 3) suggests that they provide a constant metric for self-motion (1, 3-7). Place cells in hippocampal regions CA1 and CA3 tend to fire in single firing fields (8), coding for self-location within an environment. Place cells create novel representations for new environments ("remapping") (3, 9, 10) providing a neural substrate for memory; they show attractor dynamics (11-13) and long-term plasticity (14), and they become increasingly stable and focal with prolonged experience of an environment (15,16). In contrast, grid cells are thought to retain their regular spatial structure, scale, and position relative to other grids in novel environments (1, 3), changing only their orientation and spatial offset relative to the environment and showing a brief reduction in spatial stability (1). Grid cells (1,7,17), in conjunction with other environmental inputs (6,(18)(19)(20)(21), are thought to provide an important input to hippocampal place cells. Conversely, direct and indirect projections from CA1 to the deep layers of the mEC (22, 23) have been proposed as a possibly route by which extrinsic sensory information might reach grids (21), a view supported by developmental and inactivation studies (24-26). Together, these points raise questions about the relationship between entorhinal and hippocampal activity; for example: Does stable grid cell firing co-occur with labile place fields, and what drives place cell remapping?In experiment 1, we investigated grid cell firing on first exposure to a new environment and as it became increasingly familiar during trials conducted on the same day and then on subsequent days. In experiment 2, we replicated the experiment using different environments, while corecording grid cells and place cells from a second cohort of rats that had received bilateral mEC and hippocampal implants. Together, these experiments showed that grid cell firing patterns were spatially expanded and less regular in novel arenas than in a similarly size...

Context-dependent spatially periodic activity in the human entorhinal cortex

“…Barry et al (19) showed that manipulations to the width and length of a familiar enclosure resulted in similar transformations of the rodents' grids: When the familiar environment was elongated, the grid patterns elongated similarly. Also in rats, grids have been shown to display expansion upon introduction to a novel environment and then relax back to the original scale when the environment becomes familiar (18). Combined, these results suggest that grid cells might have a default scale but that the default scale could be influenced by experience in the given environment.…”

“…The largest dataset included neurons classified as displaying significant spatially periodic activity based on spatial spectral analysis of the single units. The other two smaller datasets were both classified as "putative grid cells" (PGCs) based on their conformity of gridness scores to the definition used in studies and referred to herein as the Barry-Krupic (BK) method (11,18). The difference between the second and third datasets was that the third dataset, in addition to being defined based on the BK method, was subjected to a thorough validation against theta modulation and directional tuning.…”

“…Accordingly, grids recorded in circular or symmetrical enclosures tend to exhibit a narrow range of 60 ± 5°r otational symmetry quantified from autocorrelograms (ACs) (18). However, a comprehensive analysis of spatial periodicity evident from cells in the presubiculum and medial EC of rats revealed that only about 35-50% of medial EC cells exhibited canonical 60°ro-tational symmetry (12% and 28% in the presubiculum and parasubiculum, respectively) (11,22), whereas a significant fraction of medial EC neurons (43%) displayed spatially periodic activity different from the 60°rotational symmetry (11).…”

“…The two neuroanatomical subsystems are thought to complement each other such that individual place cells represent specific spatial locations and grid cells provide an environment-invariant metric upon which to reference the agent's (animal or human) location (12). Although the adaptive flexibility of spatial tuning of neurons in the rodent hippocampus is evident from remapping their receptive fields when switching between environments (13)(14)(15)(16)(17), the association between grid patterns of cells in the EC and the environment is less clear (13,(18)(19)(20). Here, we focus on three main features of grid-cell patterns: scale invariance, orientation, and rotational symmetry.…”

Grid cells and cortical representation

“…Within modules of grid cells, cell assemblies respond with coherent changes in grid phase, grid orientation and grid scale when the animal is brought to a different environment 12,24 or following interventions that change the scale of the grid, such as exposure to an unfamiliar environment 25,78,79 or compression of the recording enclosure 24,25 . In each case, the relationship between firing fields of cell pairs is conserved despite major changes in the properties of individual cells and without any obvious relationship to sensory inputs 78 .…”