Sensory Feedback, Error Correction, and Remapping in a Multiple Oscillator Model of Place-Cell Activity

Mammals navigate by integrating self-motion signals (“path integration”) and occasionally fixing on familiar environmental landmarks. The rat hippocampus is a model system of spatial representation in which place cells are thought to integrate both sensory and spatial information from entorhinal cortex. The localized firing fields of hippocampal place cells and entorhinal grid-cells demonstrate a phase relationship with the local theta (6–10 Hz) rhythm that may be a temporal signature of path integration. However, encoding self-motion in the phase of theta oscillations requires high temporal precision and is susceptible to idiothetic noise, neuronal variability, and a changing environment. We present a model based on oscillatory interference theory, previously studied in the context of grid cells, in which transient temporal synchronization among a pool of path-integrating theta oscillators produces hippocampal-like place fields. We hypothesize that a spatiotemporally extended sensory interaction with external cues modulates feedback to the theta oscillators. We implement a form of this cue-driven feedback and show that it can retrieve fixed points in the phase code of position. A single cue can smoothly reset oscillator phases to correct for both systematic errors and continuous noise in path integration. Further, simulations in which local and global cues are rotated against each other reveal a phase-code mechanism in which conflicting cue arrangements can reproduce experimentally observed distributions of “partial remapping” responses. This abstract model demonstrates that phase-code feedback can provide stability to the temporal coding of position during navigation and may contribute to the context-dependence of hippocampal spatial representations. While the anatomical substrates of these processes have not been fully characterized, our findings suggest several signatures that can be evaluated in future experiments

Hippocampal Global Remapping Can Occur without Input from the Medial Entorhinal Cortex.

The high storage capacity of the episodic memory system relies on distinct representations for events that are separated in time and space. The spatial component of these computations includes the formation of independent maps by hippocampal place cells across environments, referred to as global remapping. Such remapping is thought to emerge by the switching of input patterns from specialized spatially selective cells in medial entorhinal cortex (mEC), such as grid and border cells. Although it has been shown that acute manipulations of mEC firing patterns are sufficient for inducing hippocampal remapping, it remains unknown whether specialized spatial mEC inputs are necessary for the reorganization of hippocampal spatial representations. Here, we examined remapping in rats without mEC input to the hippocampus and found that highly distinct spatial maps emerged rapidly in every individual rat. Our data suggest that hippocampal spatial computations do not depend on inputs from specialized cell types in mEC

Hippocampal-Prefrontal theta oscillations support memory integration

Integration of separate memories forms the basis of inferential reasoning—an essential cognitive process that enables complex behavior. Considerable evidence suggests that both hippocampus and medial prefrontal cortex (mPFC) play a crucial role in memory integration. Although previous studies indicate that theta oscillations facilitate memory processes, the electrophysiological mechanisms underlying memory integration remain elusive. To bridge this gap, we recorded magnetoencephalography data while participants performed an inference task and employed novel source reconstruction techniques to estimate oscillatory signals from the hippocampus. We found that hippocampal theta power during encoding predicts subsequent memory integration. Moreover, we observed increased theta coherence between hippocampus and mPFC. Our results suggest that integrated memory representations arise through hippocampal theta oscillations, possibly reflecting dynamic switching between encoding and retrieval states, and facilitating communication with mPFC. These findings have important implications for our understanding of memory-based decision making and knowledge acquisition

Controlling Phase Noise in Oscillatory Interference Models of Grid Cell Firing.

Oscillatory interference models account for the spatial firing properties of grid cells in terms of neuronal oscillators with frequencies modulated by the animal's movement velocity. The phase of such a "velocity-controlled oscillator" (VCO) relative to a baseline (theta-band) oscillation tracks displacement along a preferred direction. Input from multiple VCOs with appropriate preferred directions causes a grid cell's grid-like firing pattern. However, accumulating phase noise causes the firing pattern to drift and become corrupted. Here we show how multiple redundant VCOs can automatically compensate for phase noise. By entraining the baseline frequency to the mean VCO frequency, VCO phases remain consistent, ensuring a coherent grid pattern and reducing its spatial drift. We show how the spatial stability of grid firing depends on the variability in VCO phases, e.g., a phase SD of 3 ms per 125 ms cycle results in stable grids for 1 min. Finally, coupling N VCOs with similar preferred directions as a ring attractor, so that their relative phases remain constant, produces grid cells with consistently offset grids, and reduces VCO phase variability of the order square root of N. The results suggest a viable functional organization of the grid cell network, and highlight the benefit of integrating displacement along multiple redundant directions for the purpose of path integration

Controlling Phase Noise in Oscillatory Interference Models of Grid Cell Firing

Oscillatory interference models account for the spatial firing properties of grid cells in terms of neuronal oscillators with frequencies modulated by the animal's movement velocity. The phase of such a "velocity-controlled oscillator" (VCO) relative to a baseline (theta-band) oscillation tracks displacement along a preferred direction. Input from multiple VCOs with appropriate preferred directions causes a grid cell's grid-like firing pattern. However, accumulating phase noise causes the firing pattern to drift and become corrupted. Here we show how multiple redundant VCOs can automatically compensate for phase noise. By entraining the baseline frequency to the mean VCO frequency, VCO phases remain consistent, ensuring a coherent grid pattern and reducing its spatial drift. We show how the spatial stability of grid firing depends on the variability in VCO phases, e.g., a phase SD of 3 ms per 125 ms cycle results in stable grids for 1 min. Finally, coupling N VCOs with similar preferred directions as a ring attractor, so that their relative phases remain constant, produces grid cells with consistently offset grids, and reduces VCO phase variability of the order square root of N. The results suggest a viable functional organization of the grid cell network, and highlight the benefit of integrating displacement along multiple redundant directions for the purpose of path integration

Contributions of the medial etorhinal and postrhinal cortices to spatial and contextual processing

Thesis (Ph.D.)--Boston UniversityThe medial entorhinal and the postrhinal cortices are regions thought to critically mediate spatial and contextual processing in the medial temporal lobe. However, the manner by which these cortices contribute to spatial processing is not unequivocally established. In the first study, the entorhinal cortex was periodically disrupted utilizing the optogenetic inhibitory opsin, archaerhodopsin (ArchT) while the spatial firing of hippocampal neurons were recorded in adult rats. If the medial entorhinal cortex is an essential driver of spatial responses in the hippocampus, it would be expected that changes in hippocampal neuron firing would be specifically time-locked to when the inactivating laser is on. Instead, entorhinal disruption causes a subset of cells to remap only once during the repeated inactivations; once altered, the remapped cells maintain their new firing patterns irrespective of whether the laser is on or not. This remapping, however, does not lead to a net change in the spatial information coded across the hippocampal neuron population. This suggests that disrupting medial entorhinal inputs does not change the resolution of the spatial representation, but instead changes which hippocampal ensemble represents the environment. The participation of the postrhinal cortex in processing spatial contexts was examined in two experiments. The first experiment examined whether the spatial context of an object influences its perceived familiarity, and whether lesions of the postrhinal cortex diminish this effect. The second experiment of this study investigated whether animals with postrhinal ablations can use spatial context to conditionally discriminate which item contains a reward. No deficit was observed on either experiment, suggesting that the postrhinal cortex is not critical for processing spatial contexts. Though these results suggest that spatial processing is not the essential function of these cortices, they do not eliminate the possibility that spatial information may be one of several sources contributing to their computations. Overall, these studies suggest that the entorhinal and postrhinal cortices use multidimensional information to bias which ensembles are active in the medial temporal lobe, thereby dictating how objects and their relationships are processed

The Neural Computations of Spatial Memory from Single Cells to Networks

Studies of spatial memory provide valuable insight into more general mnemonic functions, for by observing the activity of cells such as place cells, one can follow a subject’s dynamic representation of a changing environment. I investigate how place cells resolve conflicting neuronal input signals by developing computational models that integrate synaptic inputs on two scales. First, I construct reduced models of morphologically accurate neurons that preserve neuronal structure and the spatial specificity of inputs. Second, I use a parallel implementation to examine the dynamics among a network of interconnected place cells. Both models elucidate possible roles for the inputs and mechanisms involved in spatial memory

The role of the medial entorhinal cortex in spatial and temporal coding

The hippocampus (HIPP) is the core of a memory system crucial for the formation of new episodic (unique event) memories in humans and episodic-like memories (for what, where and when) in rodents. Its prevalent role in the formation of memories is thought to rely on a variety of specialized neural network computations: It is for example believed that hippocampal networks associate information about different aspects of an experience (such as a particular event and the place at which the event occurred) into a coherent memory trace. In order to prevent interference between memories that are similar (such as two different experiences within the same place) each memory is assigned a neural code that is highly distinct from those for previously acquired memories. Finally, hippocampal networks are thought to fuse memories for individual fragments of an experience into a temporally structured sequence which represent an episode. Information about different aspects of an experience reaches the HIPP via the entorhinal cortex (EC), which is its major cortical input structure. Electrophysiological single-unit recordings in behaving rodents revealed that in particular the medial division of the EC (MEC) contains a variety of cell types that are specialized in the representation of spatial and self-motion information. It is therefore believed that input from the MEC supports the spatial component of memory processing in the HIPP. Here, we tested the long-standing hypothesis that hippocampal spatial coding relies on input from the MEC. This was achieved by performing extensive, bilateral excitotoxic lesions of the MEC and placing electrode arrays into the CA1 pyramidal cell layer of the HIPP. Hippocampal neural computations were assessed by recording extracellular action potentials (APs) from individual neurons as rats explored open field environments. The firing patterns of hippocampal neurons are known to correlate with the rat’s behavior, in that each cell fires APs at restricted proportions of the environment, forming spatial receptive fields (so-called place fields). The spatial precision and organization of those place fields was examined in control and MEC-lesioned rats. We found that hippocampal neurons retained their spatial selectivity after MEC lesions, even though the precision and stability of the hippocampal spatial code were reduced. The ability to form distinct spatial representation for different environments was entirely intact in MEC-lesioned rats. Contrary to most contemporary theories of hippocampo-entorhinal function, our findings suggest that the MEC is not the only determinant of hippocampal spatial computations and that sources lacking sophisticated spatial firing, such as the lateral division of the entorhinal cortex (LEC) and local hippocampal network computations are sufficient to support this function. Following the finding that spatial firing was partly preserved in MEC-lesioned rats, we tested whether the MEC is necessary for the temporal organization of spike timing within the place field. Hippocampal place cells that are activated along the rat’s trajectory through space are thought to be linked into synaptically connected neuronal sequences via a mechanisms referred to as hippocampal theta phase precession (hTPP). Theta phase precession reflects the temporal distribution of APs within each place field with reference to the local field potential (LFP) oscillation at theta frequency (4 to 10 Hz). We found that hTPP was strongly disrupted in MEC-lesioned rats, demonstrating that the MEC is necessary for the temporal organization of hippocampal spatial firing. Cognitive functions that rely on sequentially activated place cells are thus likely to rely on the MEC. In summary, the presented data demonstrate that the contribution of the MEC to hippocampal spatial coding is less predominant than postulated by contemporary theories of hippocampo-entorhinal function. In addition, the findings suggest that the MEC, which is widely considered a spatial processing center of the brain, supports memory through the temporal organization of hippocampal spatial firing