Place Field Location Research Articles

Preexisting hippocampal network dynamics constrain optogenetically induced place fields

Memory models often emphasize the need to encode novel patterns of neural activity imposed by sensory drive. Prior learning and innate architecture likely restrict neural plasticity, however. Here, we test how the incorporation of synthetic hippocampal signals is constrained by preexisting circuit dynamics. We optogenetically stimulated small groups of CA1 neurons as mice traversed a chosen segment of a linear track, mimicking the emergence of place fields. Stimulation induced persistent place field remapping in stimulated and non-stimulated neurons. The emergence of place fields could be predicted from sporadic firing in the new place field location and the temporal relationship to peer neurons before the optogenetic perturbation. Circuit modification was reflected by altered spike transmission between connected pyramidal cells and inhibitory interneurons, which persisted during post-experience sleep. We hypothesize that optogenetic perturbation unmasked sub-threshold place fields. Plasticity in recurrent/lateral inhibition may drive learning through the rapid association of existing states.

Spatially dispersed synapses yield sharply-tuned place cell responses through dendritic spike initiation.

Key points The generation of dendritic spikes and the consequent sharp tuning of neuronal responses are together attainable even when iso‐feature synapses are randomly dispersed across the dendritic arbor.Disparate combinations of channel conductances with distinct configurations of randomly dispersed place field synapses concomitantly yield similar sharp tuning profiles and similar functional maps of several intrinsic properties.Targeted synaptic plasticity converts silent cells to place cells for specific place fields in models with disparate channel combinations that receive dispersed synaptic inputs from multiple place field locations.Dispersed localization of iso‐feature synapses is a strong candidate for achieving sharp feature selectivity in neurons across sensory‐perceptual systems, with several degrees of freedom in relation to synaptic locations.Quantitative evidence for the possibility that degeneracy (i.e. the ability of disparate structural components to yield similar functional outcomes) could act as a broad framework that effectively accomplishes the twin goals of input‐feature encoding and homeostasis of intrinsic properties without cross interferences. A prominent hypothesis spanning several sensory‐perceptual systems implicates spatially clustered synapses in the generation of dendritic spikes that mediate sharply‐tuned neuronal responses to input features. In this conductance‐based morphologically‐precise computational study, we tested this hypothesis by systematically analysing the impact of distinct synaptic and channel localization profiles on sharpness of spatial tuning in hippocampal pyramidal neurons. We found that the generation of dendritic spikes, the emergence of an excitatory ramp in somatic voltage responses, the expression of several intrinsic somatodendritic functional maps and sharp tuning of place‐cell responses were all attainable even when iso‐feature synapses are randomly dispersed across the dendritic arbor of models with disparate channel combinations. Strikingly, the generation and propagation of dendritic spikes, reliant on dendritic sodium channels and N‐methyl‐d‐asparate receptors, mediated the sharpness of spatial tuning achieved with dispersed synaptic localization. To ensure that our results were not artefacts of narrow parametric choices, we confirmed these conclusions with independent multiparametric stochastic search algorithms spanning thousands of unique models for each synaptic localization scenario. Next, employing virtual knockout models, we demonstrated a vital role for dendritically expressed voltage‐gated ion channels, especially the transient potassium channels, in maintaining sharpness of place‐cell tuning. Importantly, we established that synaptic potentiation targeted to afferents from one specific place field was sufficient to impart place field selectivity even when intrinsically disparate neurons received randomly dispersed afferents from multiple place field locations. Our results provide quantitative evidence for disparate combinations of channel and synaptic localization profiles to concomitantly yield similar tuning and similar intrinsic properties.

Hippocampal ensemble dynamics timestamp events in long-term memory.

The capacity to remember temporal relationships between different events is essential to episodic memory, but little is currently known about its underlying mechanisms. We performed time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environments. Longitudinal analysis exposed ongoing environment-independent evolution of episodic representations, despite stable place field locations and constant remapping between the two environments. These dynamics time-stamped experienced events via neuronal ensembles that had cellular composition and activity patterns unique to specific points in time. Temporally close episodes shared a common timestamp regardless of the spatial context in which they occurred. Temporally remote episodes had distinct timestamps, even if they occurred within the same spatial context. Our results suggest that days-scale hippocampal ensemble dynamics could support the formation of a mental timeline in which experienced events could be mnemonically associated or dissociated based on their temporal distance.

Remapping-like changes in place field activity through dopaminergic action

Event Abstract Back to Event Remapping-like changes in place field activity through dopaminergic action Moritz Von Heimendahl1* and Michael Brecht1 1 Humboldt Universität, Bernstein Center for Compuational Neuroscience, Germany The phenomenon of hippocampal remapping has received sustained attention ever since its discovery. Remapping is striking because usually, most place cells in the rodent hippocampus show stable response properties over weeks and more. However, strong changes in the environment lead to global remapping, whereby most place cells change their firing fields drastically or shut down altogether, while new, previously silent cells become active. While the kind of environmental cues that elicit remapping have been studied in detail, it is still unclear what kind of internal signal prompts the otherwise so stable place representations to change all at once. Dopamine is often discussed as a potential novelty signal and here we investigated the effects of dopamine agonists on place cell activity. To this end, we recorded the spatial response properties of pyramidal cells in the dorsal hippocampus of rats while they freely explored an environment. Systemic injection of the nonspecific dopamine agonist apomorphine, but not of saline, led to changes in place field locations of many cells, similar to changes observed in global remapping. In further experiments, the dose-dependence, role of the specific receptor subtypes, and the effect of dopamine antagonists were examined. The finding that dopaminergic action induces remapping-like place field changes shows that global remapping can occur in the absence of environmental changes. Pharmacological manipulation opens up new avenues to analyze the mechanisms underlying global remapping. Acknowledgements This work was supported by Humboldt Universität zu Berlin, the Bernstein Center for Computational Neuroscience Berlin, the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) (Förderkennzeichen 01GQ1001A), Neurocure, and a European Research Council grant (M.B.). We thank Brigitte Geue and Undine Schneeweiss for technical assistance. Keywords: Dopamine, Hippocampus, remapping Conference: Bernstein Conference 2012, Munich, Germany, 12 Sep - 14 Sep, 2012. Presentation Type: Poster Topic: Learning, plasticity, memory Citation: Von Heimendahl M and Brecht M (2012). Remapping-like changes in place field activity through dopaminergic action. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference 2012. doi: 10.3389/conf.fncom.2012.55.00199 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 May 2012; Published Online: 12 Sep 2012. * Correspondence: Dr. Moritz Von Heimendahl, Humboldt Universität, Bernstein Center for Compuational Neuroscience, Berlin, 10115, Germany, moritz@heimendahl.net Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Moritz Von Heimendahl Michael Brecht Google Moritz Von Heimendahl Michael Brecht Google Scholar Moritz Von Heimendahl Michael Brecht PubMed Moritz Von Heimendahl Michael Brecht Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Modular Realignment of Entorhinal Grid Cell Activity as a Basis for Hippocampal Remapping

Hippocampal place fields, the local regions of activity recorded from place cells in exploring rodents, can undergo large changes in relative location during remapping. This process would appear to require some form of modulated global input. Grid-cell responses recorded from layer II of medial entorhinal cortex in rats have been observed to realign concurrently with hippocampal remapping, making them a candidate input source. However, this realignment occurs coherently across colocalized ensembles of grid cells (Fyhn et al., 2007). The hypothesized entorhinal contribution to remapping depends on whether this coherence extends to all grid cells, which is currently unknown. We study whether dividing grid cells into small numbers of independently realigning modules can both account for this localized coherence and allow for hippocampal remapping. To do this, we construct a model in which place-cell responses arise from network competition mediated by global inhibition. We show that these simulated responses approximate the sparsity and spatial specificity of hippocampal activity while fully representing a virtual environment without learning. Place-field locations and the set of active place cells in one environment can be independently rearranged by changes to the underlying grid-cell inputs. We introduce new measures of remapping to assess the effectiveness of grid-cell modularity and to compare shift realignments with other geometric transformations of grid-cell responses. Complete hippocampal remapping is possible with a small number of shifting grid modules, indicating that entorhinal realignment may be able to generate place-field randomization despite substantial coherence.

Impact of temporal coding of presynaptic entorhinal cortex grid cells on the formation of hippocampal place fields

Many behavioural experiments have pointed out the important role played by the hippocampus in spatial navigation. This role was enlightened by the discovery of hippocampal cells in rodents firing only at very specific locations in an environment, the so-called 'place field'. Recently, it has been observed that one synapse upstream of the hippocampus, entorhinal cells fire when the rat is located at any of the vertices of grid fields covering the environment. Furthermore, it was reported that both hippocampal and entorhinal cells have firing activity modulated by the theta local field potential in term of theta phase precession. In a previous report, the authors suggested that the temporal code driven by theta phase precession should play an important role in the building of hippocampal place cells from entorhinal grid cells. Here, with the help of a simpler computational model, we further investigate the implications of our hypothesis. We demonstrate that the nonlinear nature of the shape of the phase precession predicts that place field location are slightly backward shifted according to the direction of the rat.

Context-dependent modulation by D₁ receptors: Differential effects in hippocampus and striatum.

Place-specific firing by hippocampal and striatal neurons was recorded simultaneously following injection of a D(1) receptor antagonist (SCH23390) and during spatial working memory task performance. SCH23390-induced changes in unit responses were observed during light and dark test conditions. Although hippocampal place field locations were altered by the contextual change, the reliability and specificity of place fields was disrupted only by combining D(1) antagonism and a change in context. Striatal place field locations were reorganized after either contextual change or D(1) antagonism, without altering place field reliability and specificity. Disrupted velocity encoding by place cells in both regions was induced by darkness, whereas greater stability in acceleration encoding followed removal of D(1) receptor activity. Dopamine may differentially regulate hippocampal context learning and striatum-based predictive codes.

Self-Motion and the Hippocampal Spatial Metric

Self-motion signals are sufficient for animal navigation ("path integration") and for updating hippocampal location-specific firing. The contributions of ambulatory, vestibular, and optic self-motion signals to CA1 unit activity and EEG were studied while rats either walked or drove a car between locations on a circular track (referred to as WALK and CAR, respectively) or experienced pseudomotion, in which the animal was stationary and the environment was rotated (WORLD). Fewer pyramidal cells expressed place fields during CAR and those that did exhibited substantially larger place fields. The number of theta cycles required to traverse a place field increased, whereas the slope of the theta phase of firing versus position function was reduced. The presence and/or location of place fields were not well correlated between conditions. These effects were even more accentuated during WORLD. These results are not explainable by a simple "smearing out" of place fields but, in terms of size of place fields relative to the track size, are comparable with what would be observed if the track circumference was reduced and the animal moved around it at a correspondingly slower speed. Theta (and its 14-18 Hz harmonic) power were dependent on velocity, but the gain of this function was substantially reduced during CAR and WORLD, again as if the rat were moving more slowly. The spatial scale over which the hippocampal population vector is updated appears to be derived primarily from the gain of a self-motion velocity signal with approximately equal components derived from ambulation, vestibular, and optic-flow signals.

Functional interaction between the associative parietal cortex and hippocampal place cell firing in the rat

The hippocampus and associative parietal cortex (APC) both contribute to spatial memory but the nature of their functional interaction remains unknown. To address this issue, we investigated the effects of APC lesions on hippocampal place cell firing in freely moving rats. Place cells were recorded from APC-lesioned and control rats as they performed a pellet-chasing task in a circular arena containing three object cues. During successive recording sessions, cue manipulations including object rotation in the absence of the rat and object removal in the presence of the rat were made to examine the control exerted by the objects or by non-visual intramaze cues on place field location, respectively. Object rotations resulted in equivalent field rotation for all cells in control rats. In contrast, a fraction of place fields in APC-lesioned rats did not rotate but remained stable relative to the room. Object removal produced different effects in APC-lesioned and control rats. In control rats, most place fields remained stable relative to the previous object rotation session, indicating that they were anchored to olfactory and/or idiothetic cues. In APC-lesioned rats, a majority of place fields shifted back to their initial, standard location, thus suggesting that they relied on uncontrolled background cues to maintain place field stability. These results provide strong evidence that the hippocampus and the APC cooperate in the formation of spatial memory and suggest that the APC is involved in elaboration of a hippocampal map based on proximal landmarks.

Dorsal striatal head direction and hippocampal place representations during spatial navigation.

Several theories of basal ganglia function describe a striatal contribution to learning that is independent of hippocampal function. This study examined the question of whether the striatum should be regarded as functioning independently of or acting in concert with limbic structures. Dorsal striatal head direction cells and hippocampal place cells were recorded in parallel while rats performed a hippocampal-dependent radial maze task. Changes in the directional preference of head direction cells and the location of place fields were compared following alterations of the sensory environment. When familiar visual cues were presented in new spatial arrangements, or when new visual cues were placed in a familiar environment, rotations of directional preferences were consistent with the mean place-field response. When familiar visual and nonvisual cues were presented in conflict, or when rats were exposed to novel environments, the responses of the two cell types were inconsistent relative to each other. This pattern suggests that current perceptions and expectations of familiar spatial contexts may dynamically modulate the relationship between hippocampus and dorsal striatum.

Instability in the Place Field Location of Hippocampal Place Cells after Lesions Centered on the Perirhinal Cortex

The perirhinal cortex appears to play a key role in memory, and the neighboring hippocampus is critically involved in spatial processing. The possibility exists, therefore, that perirhinal-hippocampal interactions are important for spatial memory processes. The purpose of the present study was to investigate the contribution of the perirhinal cortex to the location-specific firing ("place field") of hippocampal complex-spike ("place") cells. The firing characteristics of dorsal CA1 place cells were examined in rats with bilateral ibotenic acid lesions centered on the perirhinal cortex (n = 4) or control surgeries (n = 5) as they foraged in a rectangular environment. The activity of individual place cells was also monitored after a delay period of either 2 min, or 1 or 24 hr, during which time the animal was removed from the environment. Although the perirhinal cortex lesion did not affect the place field size or place cell firing characteristics during a recording session, it was determined that the location of the place field shifted position across the delay period in 36% (10 of 28) of the cells recorded from lesioned animals. In contrast, none of the place cells (0 of 29) recorded from control animals were unstable by this measure. These data indicate that although the initial formation of place fields in the hippocampus is not dependent on perirhinal cortex, the maintenance of this stability over time is disrupted by perirhinal lesions. This instability may represent an erroneous "re-mapping" of the environment and suggests a role for the perirhinal cortex in spatial memory processing.

Effects of ethanol on hippocampal place-cell and interneuron activity

Mounting evidence suggests that ethanol exerts effects on learning and memory by altering cellular activity in the hippocampus and related structures. However, little is actually known regarding ethanol’s effects on hippocampal function in awake, freely-behaving animals. The present study examines the effects of ethanol on hippocampal place-cell and interneuron activity in freely-behaving rats. Signals from individual hippocampal neurons were isolated while subjects traversed a symmetric Y-maze for food reward. Following 15 min of baseline recording, subjects were injected with one of four doses of ethanol (0.0, 0.5, 1.0 and 1.5 g/kg), and cellular activity was monitored for a 1-h time period. Following sufficient time for recovery (minimum of 3 h post injection), cellular activity was monitored for an additional 15-min period. Both 1.0 and 1.5 g/kg ethanol potently suppressed the firing of hippocampal place-cells without altering place-field locations. Ethanol did not significantly suppress out-of-field firing rates, leading to a decrease in spatial specificity (i.e. the ratio of in-field/out-of-field firing rates). Interneuron activity was not altered by 1.0 g/kg ethanol, but was occasionally suppressed by 1.5 g/kg ethanol. Results are interpreted in light of recent behavioral and electrophysiological studies examining the effects of ethanol on hippocampal function.

Learned interaction of visual and idiothetic cues in the control of place field orientation.

In a symmetrical environment (like a square box) hippocampal place cells use a mixture of visual and idiothetic (movement) information to tell them which way the environment is oriented. The present experiment tested the hypothesis that if the visual landmarks were mobile, place cells would learn to disregard these and rely on idiothetic cues instead. Place cells were recorded in a square box surrounded by circular black curtains. A cue card hung on the curtain behind one of the walls to break the fourfold symmetry. The relative influence of this card on the location of place fields was assessed each day by confining the rat on a rotating platter underneath an opaque cover, and then rotating the card and the platter by different amounts, to see whether subsequently recorded place fields had rotated with the card or with the rat. For some rats, these trials had been preceded by trials in which the card had been visibly moved from trial to trial, so that the rats had seen that it was mobile. Other rats received no prior visual information that the card was mobile. In the rats that had previously seen the card move, place fields initially rotated with the card but by the end of five sessions usually rotated with the rat instead. For rats that had never seen the card move, place fields always followed the card. Thus, the cells were able to "learn" that their preferred directional input, the card, was unreliable. A third group of rats, who were covered only for 30 s while the card was moved, showed mixed behaviour, suggesting a degradation of the idiothetic trace with time.

Place field dynamics and directionality in a spatial memory task

In previous studies place fields have been shown to be governed by one or more polarizing stimuli such that rotation of the stimuli caused concomitant rotation of the fields. Place fields have also been observed to persist after removal of stimulus cues. In the present study we confirm the previous findings and report two new responses. Hippocampal place fields were observed to decrease or cease place specific firing after the removal of the polarizing cues. Others increased or initiated place specific firing after cue removal. Thus in these instances place field location was dependent on the orientation of the polarizing cues but place field magnitude was governed by their presence or absence. A subset of the place fields recorded in the present study were found to display directionality. Place field directionality was found to be governed by the polarizing cues such that cue rotation produced concomitant rotation in the direction of maximal firing. However directionally specific firing was unaffected by cue removal. These results suggest that place field directionality is initially set up by the polarizing cues but is subsequently independent of them.

A simple network model simulates hippocampal place fields: II. Computing goal-directed trajectories and memory fields.

Place cells have been described as the computational elements of a neuronal cognitive mapping system that encodes and stores relationships among spatial stimuli (O'Keefe & Nadel, 1978). Furthermore, place cells seem to encode remembered locations because neural activity is maintained when the visual stimuli that influence place field location are vastly degraded, such as when cues are removed or the lights are turned off (O'Keefe & Speakman, 1987; Quirk, Muller, & Kubie, 1990). A feed-forward network model that mapped visual input onto a representation of location simulated some basic properties of hippocampal place fields, including resistance to disruption after partial cue removal (Shapiro & Hetherington, 1993). However, the stimulated place fields required visual input for their activation. We now report that a network that incorporates feedback (a) computed correct trajectories toward simulated goals and (b) simulated place fields that persist in the absence of visual input. The simulation suggests that feedback properties can provide a computational account of O'Keefe and Speakman's data.

A computational model of hippocampal place fields.

There are neurons in the hippocampus that become active only when an animal is near a particular location in a specific environment. The activity of some of these units is known to be governed by the configuration of a small set of discrete landmarks. In order to respond in this fashion, these neurons must, in effect, be able to recognize particular locations. A model of this recognition process is described which is able to make quantitative predictions about how the response of these place-field units varies as properties of the environmental landmarks are manipulated. Computer simulations of the model show that it is consistent with the available quantitative data. These simulations also predict large, characteristic changes in place-field location and size with manipulations of the environmental landmarks. Comparison of this kind of prediction with actual experiments will serve as a test of the validity of the model.