Parallel and convergent processing in grid cell, head-direction cell, boundary cell, and place cell networks.

The brain is able to construct internal representations that correspond to external spatial coordinates. Such brain maps of the external spatial topography may support a number of cognitive functions, including navigation and memory. The neuronal building block of brain maps are place cells, which are found throughout the hippocampus of rodents and, in a lower proportion, primates. Place cells typically fire in one or few restricted areas of space, and each area where a cell fires can range, along the dorsoventral axis of the hippocampus, from 30 cm to at least several meters. The sensory processing streams that give rise to hippocampal place cells are not fully understood, but substantial progress has been made in characterizing the entorhinal cortex, which is the gateway between neocortical areas and the hippocampus. Entorhinal neurons have diverse spatial firing characteristics, and the different entorhinal cell types converge in the hippocampus to give rise to a single, spatially modulated cell type-the place cell. We therefore suggest that parallel information processing in different classes of cells-as is typically observed at lower levels of sensory processing-continues up into higher level association cortices, including those that provide the inputs to hippocampus. WIREs Cogn Sci 2014, 5:207-219. doi: 10.1002/wcs.1272 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website

Learning place cells, grid cells and invariances with excitatory and inhibitory plasticity

Neurons in the hippocampus and adjacent brain areas show a large diversity in their tuning to location and head direction, and the underlying circuit mechanisms are not yet resolved. In particular, it is unclear why certain cell types are selective to one spatial variable, but invariant to another. For example, place cells are typically invariant to head direction. We propose that all observed spatial tuning patterns – in both their selectivity and their invariance – arise from the same mechanism: Excitatory and inhibitory synaptic plasticity driven by the spatial tuning statistics of synaptic inputs. Using simulations and a mathematical analysis, we show that combined excitatory and inhibitory plasticity can lead to localized, grid-like or invariant activity. Combinations of different input statistics along different spatial dimensions reproduce all major spatial tuning patterns observed in rodents. Our proposed model is robust to changes in parameters, develops patterns on behavioral timescales and makes distinctive experimental predictions.BMBF, 01GQ1201, Lernen und Gedächtnis in balancierten Systeme

Space, Time and Learning in the Hippocampus: How Fine Spatial and Temporal Scales Are Expanded into Population Codes for Behavioral Control

The hippocampus participates in multiple functions, including spatial navigation, adaptive timing, and declarative (notably, episodic) memory. How does it carry out these particular functions? The present article proposes that hippocampal spatial and temporal processing are carried out by parallel circuits within entorhinal cortex, dentate gyrus, and CA3 that are variations of the same circuit design. In particular, interactions between these brain regions transform fine spatial and temporal scales into population codes that are capable of representing the much larger spatial and temporal scales that are needed to control adaptive behaviors. Previous models of adaptively timed learning propose how a spectrum of cells tuned to brief but different delays are combined and modulated by learning to create a population code for controlling goal-oriented behaviors that span hundreds of milliseconds or even seconds. Here it is proposed how projections from entorhinal grid cells can undergo a similar learning process to create hippocampal place cells that can cover a space of many meters that are needed to control navigational behaviors. The suggested homology between spatial and temporal processing may clarify how spatial and temporal information may be integrated into an episodic memory.National Science Foundation (SBE-0354378); Office of Naval Research (N00014-01-1-0624

Correlations and functional connections in a population of grid cells

We study the statistics of spike trains of simultaneously recorded grid cells in freely behaving rats. We evaluate pairwise correlations between these cells and, using a generalized linear model (kinetic Ising model), study their functional connectivity. Even when we account for the covariations in firing rates due to overlapping fields, both the pairwise correlations and functional connections decay as a function of the shortest distance between the vertices of the spatial firing pattern of pairs of grid cells, i.e. their phase difference. The functional connectivity takes positive values between cells with nearby phases and approaches zero or negative values for larger phase differences. We also find similar results when, in addition to correlations due to overlapping fields, we account for correlations due to theta oscillations and head directional inputs. The inferred connections between neurons can be both negative and positive regardless of whether the cells share common spatial firing characteristics, that is, whether they belong to the same modules, or not. The mean strength of these inferred connections is close to zero, but the strongest inferred connections are found between cells of the same module. Taken together, our results suggest that grid cells in the same module do indeed form a local network of interconnected neurons with a functional connectivity that supports a role for attractor dynamics in the generation of the grid pattern.Comment: Accepted for publication in PLoS Computational Biolog

Variability of grid-cell activity

Action potentials of grid cells in the entorhinal cortex of navigating rodents occur every two seconds on average. If one considers the precise temporal sequence of these events, however, it can be seen that they rarely occur in isolation. In fact, the intervals between successive action potentials can be on the order of a few milliseconds. Mapped to the trajectory of the animal, a clear clustering of the action potentials in space can be observed as well. The places where the density of such events is particularly high are called firing fields and are arranged in a hexagonal grid. Regardless of the cell characteristics, the number of spikes observed on different crossings of a field varies strongly. The time between subsequent field crossings is on the order of seconds. We found out that one cause of spike-count variability is that the exact position of the firing fields is not stable over time. In addition, the shifts of the fields were correlated across simultaneously recorded cells. This kind of non-stationarity in the grid-cell network allows conclusions to be drawn about the functioning of this system. Furthermore, dynamic field locations imply that common methods for data analysis of grid-cell recordings can be problematic. Furthermore, we found out that a subset of grid cells, which have particularly high firing rates when crossing a field, can be associated with a peculiarity in the shape of their action potentials: The spikes of some cells are followed by a short afterdepolarization (DAP). At the same time, we discovered cells with even smaller and extremely stereotypical intervals between their spikes. This group of neurons, however, exhibited less pronounced DAPs. Cells with and without DAP did not differ in their spatial firing behavior. Our results imply that different burst behaviors are not directly related to different types of spatial coding. In addition, we suggest that bursting of grid cells could be altered via the mechanisms of DAP formation. In summary, this work shows how details of neuronal activity on two different time scales provide fundamental insights into the processes of spatial navigation. Untethered firing fields and intermittent silences: Why grid‐cell discharge is so variable - Grid cells in medial entorhinal cortex are notoriously variable in their responses, despite the striking hexagonal arrangement of their spatial firing fields. Indeed, when the animal moves through a firing field, grid cells often fire much more vigorously than predicted or do not fire at all. The source of this trial‐to‐trial variability is not completely understood. By analyzing grid‐cell spike trains from mice running in open arenas and on linear tracks, we characterize the phenomenon of “missed” firing fields using the statistical theory of zero inflation. We find that one major cause of grid‐cell variability lies in the spatial representation itself: firing fields are not as strongly anchored to spatial location as the averaged grid suggests. In addition, grid fields from different cells drift together from trial to trial, regardless of whether the environment is real or virtual, or whether the animal moves in light or darkness. Spatial realignment across trials sharpens the grid representation, yielding firing fields that are more pronounced and significantly narrower. These findings indicate that ensembles of grid cells encode relative position more reliably than absolute position. Spike Afterpotentials Shape the In Vivo Burst Activity of Principal Cells in Medial Entorhinal Cortex - Principal neurons in rodent medial entorhinal cortex (MEC) generate high-frequency bursts during natural behavior. While in vitro studies point to potential mechanisms that could support such burst sequences, it remains unclear whether these mechanisms are effective under in vivo conditions. In this study, we focused on the membrane-potential dynamics immediately following action potentials (APs), as measured in whole-cell recordings from male mice running in virtual corridors (Domnisoru et al., 2013). These afterpotentials consisted either of a hyperpolarization, an extended ramp-like shoulder, or a depolarization reminiscent of depolarizing afterpotentials (DAPs) recorded in vitro in MEC principal neurons. Next, we correlated the afterpotentials with the cells' propensity to fire bursts. All DAP cells with known location resided in Layer II, generated bursts, and their interspike intervals (ISIs) were typically between 5 and 15 ms. The ISI distributions of Layer-II cells without DAPs peaked sharply at around 4 ms and varied only minimally across that group. This dichotomy in burst behavior is explained by cell-group-specific DAP dynamics. The same two groups of bursting neurons also emerged when we clustered extracellular spike-train autocorrelations measured in real 2D arenas (Latuske et al., 2015). Apart from slight variations in grid spacing, no difference in the spatial coding properties of the grid cells across all three groups was discernible. Layer III neurons were only sparsely bursting (SB) and had no DAPs. As various mechanisms for modulating ion-channels underlying DAPs exist, our results suggest that temporal features of MEC activity can be altered while maintaining the cells' overall spatial tuning characteristics