Grid cell spatial tuning reduced following systemic muscarinic receptor blockade

Abstract

Grid cells of the medial entorhinal cortex exhibit a periodic and stable pattern of spatial tuning that may reflect the output of a path integration system. This grid pattern has been hypothesized to serve as a spatial coordinate system for navigation and memory function. The mechanisms underlying the generation of this characteristic tuning pattern remain poorly understood. Systemic administration of the muscarinic antagonist scopolamine flattens the typically positive correlation between running speed and entorhinal theta frequency in rats. The loss of this neural correlate of velocity, an important signal for the calculation of path integration, raises the question of what influence scopolamine has on the grid cell tuning as a read out of the path integration system. To test this, the spatial tuning properties of grid cells were compared before and after systemic administration of scopolamine as rats completed laps on a circle track for food rewards. The results show that the spatial tuning of the grid cells was reduced following scopolamine administration. The tuning of head direction cells, in contrast, was not reduced by scopolamine. This is the first report to demonstrate a link between cholinergic function and grid cell tuning. This work suggests that the loss of tuning in the grid cell network may underlie the navigational disorientation observed in Alzheimer's patients and elderly individuals with reduced cholinergic tone.

Systemic administration of two different anxiolytic drugs decreases local field potential theta frequency in the medial entorhinal cortex without affecting grid cell firing fields

“…However, there was a significant decrease in slope after diazepam administration and in some recording sessions the slope was negative across running speeds. However even when this occurred, no changes in gridness or spacing were seen, despite this being predicted to be the case based on previous experimental results (Barry et al, 2007; Newman et al, 2013, 2014). This could be because the overall change in slope was actually quite small in comparison to the change that occurs in novel environment experiments (Barry et al, 2007) so even if there was a change in grid scale it might have been too small to detect.…”

Grid cell firing patterns may arise from feedback interaction between intrinsic rebound spiking and transverse traveling waves with multiple heading angles

“…A change in acetylcholine levels could cause a shift in overall speed modulation (Newman et al, 2013, 2014), or could be directly involved in modulating intrinsic resonance frequency relative to running speed. Acetylcholine levels have been shown to change in running vs. stationary rats (Mizuno et al, 1991; Marrosu et al, 1995) and have been shown to change the resonance frequency of medial entorhinal neurons (Heys et al, 2010; Heys and Hasselmo, 2012).…”

Characterization of exploratory activity and learning ability of healthy and “schizophrenia-like” rats in a square corridor system (AMBITUS)

“…It is well-known that in contrast to a hole-board with an open field, where the rats can show significant anxiety, rats prefer the narrow tunnels (Kimchi & Terkel, 2004). Based on this assumption, some laboratories have applied a circular corridor with or without a few side-boxes containing food rewards to evaluate the exploratory activity and/or learning abilities with a video-tracking system (Nadal, Rotllaant, Marquez, & Armario, 2005;Wikenheiser, Stephens, & Redish, 2013;Wikenheiser & Redish, 2015;Wikenheiser & Redish, 2011;Monaco, Rao, Roth, & Knierim, 2014;Newman, Climer, & Hasselmo, 2014). Unfortunately, both methods may require time-consuming data collection and/or they need long training sessions, or the commercial video-tracking systems (e.g., EthoVision XT) require special softwares which can analyze precisely the behavior of the animals.…”