Impaired Path Integration and Grid Cell Spatial Periodicity in Mice Lacking GluA1-Containing AMPA Receptors

Abstract

The hippocampus and the parahippocampal region have been proposed to contribute to path integration. Mice lacking GluA1-containing AMPA receptors (GluA1 Ϫ/Ϫ mice) were previously shown to exhibit impaired hippocampal place cell selectivity. Here we investigated whether path integration performance and the activity of grid cells of the medial entorhinal cortex (MEC) are affected in these mice. We first tested GluA1 Ϫ/Ϫ mice on a standard food-carrying homing task and found that they were impaired in processing idiothetic cues. To corroborate these findings, we developed an L-maze task that is less complex and is performed entirely in darkness, thereby reducing numerous confounding variables when testing path integration. Also in this task, the performance of GluA1 Ϫ/Ϫ mice was impaired. Next, we performed in vivo recordings in the MEC of GluA1 Ϫ/Ϫ mice. MEC neurons exhibited altered grid cell spatial periodicity and reduced spatial selectivity, whereas head direction tuning and speed modulation were not affected. The firing associations between pairs of neurons in GluA1 Ϫ/Ϫ mice were stable, both in time and space, indicating that attractor states were still present despite the lack of grid periodicity. Together, these results support the hypothesis that spatial representations in the hippocampal-entorhinal network contribute to path integration.

The Neurobiology of Mammalian Navigation

“…Interestingly, GluA1 knockout mice, which show disrupted grid cells and impaired path integration [121], show impaired theta-frequency mechanisms [121] and impaired short-term habituation [122], the latter potentially indicating that time passes more slowly for these mice. We hypothesise that time cells in these mice, while showing the expected stage-insequence properties, will exhibit longer firing durations.…”

Short-term sleep deprivation disrupts the molecular composition of ionotropic glutamate receptors in entorhinal cortex and impairs the rat spatial reference memory

“…Among the neurotransmitter receptors, the ionotropic glutamate receptors, especially the 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs), mediate the basic excitatory synaptic transmission, and are critical for formation of grid cells in EC and the related spatial cognition [25][26][27][28]. AMPARs and NMDARs function as tetramers that are assembled from GluA1-4 and GluN1-3, respectively [25].…”

Novelty-Induced Phase-Locked Firing to Slow Gamma Oscillations in the Hippocampus: Requirement of Synaptic Plasticity

“…However, conventional pharmacological and transgenic methods have limited applications due to brain-wide effects, such as cognitive and behavioral impairments, which make it unclear whether the observed changes in neuronal firing are caused directly by the interference of the cellular machinery or indirectly by the systemic deficits affecting input activity to the monitored neurons (Allen et al, 2014;Bach et al, 1995;Cain, 1997;Giese et al, 1998;Morris et al, 1986;Reisel et al, 2002;Resnik et al, 2012;Tsien et al, 1996). To circumvent this limitation, we devised a new approach combining viral vector-mediated local genetic manipulation with a unit recording technique.…”