Modulating medial septal cholinergic activity reduces medial entorhinal theta frequency without affecting speed or grid coding.

Medial septal inputs to the hippocampal system are crucial for aspects of temporal and spatial processing, such as theta oscillations and grid cell firing. However, the precise contributions of the medial septum's cholinergic neurones to these functions remain unknown. Here, we recorded neuronal firing and local field potentials from the medial entorhinal cortex of freely foraging mice, while modulating the excitability of medial septal cholinergic neurones. Alteration of cholinergic activity produced a reduction in the frequency of theta oscillations, without affecting the slope of the non-linear theta frequency vs running speed relationship observed. Modifying septal cholinergic tone in this way also led mice to exhibit behaviours associated with novelty or anxiety. However, grid cell firing patterns were unaffected, concordant with an absence of change in the slopes of the theta frequency and firing rate speed signals thought to be used by grid cells.

Task Demands Predict a Dynamic Switch in the Content of Awake Hippocampal Replay.

Reactivation of hippocampal place cell sequences during behavioral immobility and rest has been linked with both memory consolidation and navigational planning. Yet it remains to be investigated whether these functions are temporally segregated, occurring during different behavioral states. During a self-paced spatial task, awake hippocampal replay occurring either immediately before movement toward a reward location or just after arrival at a reward location preferentially involved cells consistent with the current trajectory. In contrast, during periods of extended immobility, no such biases were evident. Notably, the occurrence of task-focused reactivations predicted the accuracy of subsequent spatial decisions. Additionally, during immobility, but not periods preceding or succeeding movement, grid cells in deep layers of the entorhinal cortex replayed coherently with the hippocampus. Thus, hippocampal reactivations dynamically and abruptly switch between operational modes in response to task demands, plausibly moving from a state favoring navigational planning to one geared toward memory consolidation.

Coordinated grid and place cell replay during rest.

Hippocampal replay has been hypothesized to underlie memory consolidation and navigational planning, yet the involvement of grid cells in replay is unknown. During replay we found grid cells to be spatially coherent with place cells, encoding locations 11 ms delayed relative to the hippocampus, with directionally modulated grid cells and forward replay exhibiting the greatest coherence with the CA1 area of the hippocampus. This suggests grid cells are engaged during the consolidation of spatial memories to the neocortex.

Distorted Grids as a Spatial Label and Metric.

Grid cells have been proposed to encode both the self-location of an animal and the relative position of locations within an environment. We reassess the validity of these roles in light of recent evidence demonstrating grid patterns to be less temporally and spatially stable than previously thought.

Grid cells form a global representation of connected environments.

The firing patterns of grid cells in medial entorhinal cortex (mEC) and associated brain areas form triangular arrays that tessellate the environment [1, 2] and maintain constant spatial offsets to each other between environments [3, 4]. These cells are thought to provide an efficient metric for navigation in large-scale space [5-8]. However, an accurate and universal metric requires grid cell firing patterns to uniformly cover the space to be navigated, in contrast to recent demonstrations that environmental features such as boundaries can distort [9-11] and fragment [12] grid patterns. To establish whether grid firing is determined by local environmental cues, or provides a coherent global representation, we recorded mEC grid cells in rats foraging in an environment containing two perceptually identical compartments connected via a corridor. During initial exposures to the multicompartment environment, grid firing patterns were dominated by local environmental cues, replicating between the two compartments. However, with prolonged experience, grid cell firing patterns formed a single, continuous representation that spanned both compartments. Thus, we provide the first evidence that in a complex environment, grid cell firing can form the coherent global pattern necessary for them to act as a metric capable of supporting large-scale spatial navigation.