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Space in the brain: cells, circuits, codes and cognition

Event

Starts:

May
012013

09:00

Ends:

May
032013

17:00

Location

Kavli Royal Society Centre, Chicheley Hall, Newport Pagnell, Buckinghamshire, MK16 9JJ

Overview

Theo Murphy international scientific meeting organised by Dr Tom Hartley, Professor John O’Keefe FRS, Professor Neil Burgess and Dr Colin Lever

Event details

Recent discoveries have revealed the microstructure of the brain's representation of self-location in the hippocampal formation, providing an ideal model system for investigating the neural codes of memory and cognition. This meeting will integrate advances in optogenetics, virtual-reality, inducible transgenics, neuroimaging and computational neuroscience to define the neural mechanisms of navigation, with implications extending to behavioural genetics, robotics and medicine.

Biographies of the organisers and speakers are available below. Recorded audio of the presentations will be available on this page shortly after the event.

Enquiries: Contact the events team.

Event organisers

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Schedule of talks

Session 1: Cells

6 talks Show detail Hide detail

Attractor-based reliability-weighted decision-making in the head direction system

Professor Kate Jeffery, University College London, UK

Abstract

“Knowledge” in the brain is built up from the convergence of sensory information from different sources, and a key task for cognitive neuroscientists is to understand how this information is pieced together. An ideal model system for this task is the head direction (HD) signal, which indicates which way an animal is facing: this signal arises from a convergence of external environmental cues and internal self-motion information, and is a paradigmatic case of sensory integration.

In this talk I will present experiments with HD cells in which we examine how the cells learn to decide how much to “trust” a landmark. Two contrasting theoretical frameworks, attractor models and Bayesian integration models, make different predictions about how the system should make this decision. Our data from single neuron recordings made in awake, freely exploring animals support both possibilities and suggest a possible reconciliation of these two frameworks, possibly providing general principles for cue integration in sensory systems.

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Chair

Dr Tom Hartley, University of York, UK

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Neural codes for 2-D and 3-D space in the hippocampal formation of bats

Professor Nachum Ulanovsky, Weizmann Institute, Israel

Abstract

The work in our lab focuses on understanding the neural basis of spatial behaviors and spatial cognition in freely-moving, freely behaving mammals – employing the echolocating bat as a novel animal model.  I will describe our recent studies, including: (i) recordings of 3-D head-direction cells in the presubiculum of crawling bats, as well as recordings from hippocampal 3-D place cells in freely-flying bats, using a custom neural telemetry system – which revealed an elaborate 3-D spatial representation in the brain; and (ii) recordings of grid cells in the bat's medial entorhinal cortex, in the absence of theta oscillations – which argues against theta-based computational models of grid formation.  I will also describe our recent studies of spatial memory and navigation of fruit bats in the wild, using micro-GPS devices, which revealed outstanding navigational abilities and provided the first evidence for a large-scale cognitive map in a mammal.

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Optogenetic analysis of spatial input to the hippocampus

Professor May-Britt Moser, NTNU, Norway

Abstract

The mammalian space circuit is known to contain several functionally specialized cell types, such as place cells in the hippocampus and grid cells, head direction cells and border cells in the medial entorhinal cortex (MEC), but the interaction between these cells is poorly understood.We used a combined optogenetic-electrophysiological strategy to determine the functional identity of entorhinal cells with output to the place-cell population in the hippocampus. Channelrhodopsin-2 (ChR2) was expressed selectively in the hippocampus-targeting subset of entorhinal projection neurons by injecting retrogradely transportable ChR2-coding recombinant adeno-associated viruses in the hippocampus. Virally transduced ChR2-expressing cells were identified in MEC as cells that fired at fixed minimal latencies in response to local flashes of light. A large number of responsive cells were grid cells but short-latency firing was also induced in border cells and head direction cells, as well as nonspatial cells and cells with irregular firing fields, suggesting that place signals may be generated by convergence of signals from a broad spectrum of entorhinal functional cell types, with grid cells being the predominant spatial cell type but not the only one. The presence of a dual spatial input, from grid cells and border cells, is consistent with the idea that place cells have access to both self-motion and landmark-based information, and raises the possibility that the spatial metric of the place cell population originates from grid cells whereas boundary and landmark-induced firing is derived directly from border cells. The dual nature of the spatial input may account for the observation that place cells precede mature grid cells during ontogenesis of the spatial representation system and that place cells can maintain location specificity under conditions that reduce grid-cell periodicity in adult rats. Convergent input from a broad spectrum of entorhinal cell types may also enable individual place cells to respond dynamically, favouring different types of input in different states or under different behavioural circumstances.

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Spatial cells in the subiculum: boundary and grid signalling

Dr Colin Lever, University of Durham, UK

Abstract

I will present recent work on boundary vector cells and grid cells in the rat subiculum. One of the central predictions of boundary vector cell (BVC) model is the creation of an extra field when an additional boundary intersects a BVC’s receptive field. We show such field repetition in boundary vector cells elicited by barriers and drop edges. I will also describe initial work probing the limits of what the BVCs treat as a boundary. While recording BVCs, we have also recorded grid cells in the subiculum. Their spatial properties seem similar to entorhinal grids to date. For instance, scale depends upon anatomical location along the long axis of the dorsal subiculum, and rescaling (expansion) and orientation shifts occur upon environmental manipulation (wall removal in our case). I will briefly present effects of barrier insertion on grid cell firing. In summary, we observe that environmental boundaries exert a strong influence on both boundary and grid cells.

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Spatially periodic cells in the parahippocampal region

Dr Julija Krupic, University College London, UK

Abstract

The mammalian hippocampal formation provides neuronal representations of environmental location, but the underlying mechanisms are unclear. I will present a class of cells with spatially periodic firing patterns composed of plane waves (or bands) drawn from a discrete set of orientations and wavelengths. The majority of cells recorded in parasubicular and medial entorhinal cortices of freely moving rats belonged to this class. Grids cells form an important subset of this more general class, corresponding to hexagonal configurations of bands, and having the most stable firing. Occasional changes between hexagonal and non-hexagonal firing patterns imply a common mechanism underlying the various spatial patterns. I will show how the geometry of the environment can affect the symmetry of spatially periodic cells and will propose a descriptive model based on boundary-grid cell interactions that can capture our current experimental observations.

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Session 2: Circuits

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Architecture of spatial circuits in the hippocampal region

Abstract

The hippocampal region contains a diversity of neural circuits and functionally specialized cell types involved in the representation of self-location. Our understanding of the wiring between and within the different subregions that make up the hippocampal formation and the parahippocampal region has changed. Initially, the system appeared neatly organized, with individual functional cell-types belonging to unique neuronal networks, organized as a serial information processor. This has led to various attempts to causally relate network architecture within and between these unique circuits to functional outcome. In my presentation I will argue that the classic serial view no longer faithfully describes the organization of the region. I will focus on MEC, its intrinsic network and how this relates to the cortex on the one hand and the hippocampus on the other hand. Experimental data indicate that it is time to replace the serial concept with a complex combination of multiple parallel networks to which embedded feedback and feedforward connectivity needs to be added. Integrating specific local inhibitory networks will be the next step needed in order to fully grasp the potential functional complexity of the system.

Coauthors:
Cathrin B Canto, Jonathan J Couey, Noriko Koganezawa, Kally C O’Reilly

Chair

Dr Colin Lever, University of Durham, UK

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Development of the HF spatial system: grid, boundary, head direction and place cells

Dr Tom Wills, University College London, UK

Abstract

In order to understand when and how the hippocampal neural representation of space is created during development, we recorded the activity of single neurons from awake and behaving pre-weanling rat pups from P12 onwards.

Confirming previous findings, we find that Head Direction Cells represent the earliest developing spatial signal, with stable Head Direction cells emerging in the dorsal pre-subiculum at P14. Several characteristics of both Head Direction and Grid cells’ firing indicate that an adult-like network is present soon after spatially-tuned firing is first observed. In particular, network behaviour consistent with continuous attractor models was present from the earliest ages that spatial firing could be detected.

By contrast, we find that Place Cell firing matures gradually. Although adult-like place cells can be seen at P14, the CA1 network is not fully mature until several weeks of age. What are the inputs that support Place Cell firing in the youngest animals? We find evidence that, as for adults, place fields are bound to configurations of multiple cues, and that the geometry of environmental boundaries may be one of the earliest spatial features capable of stabilising Place Cell responses.

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Engrams for genuine and false memories

Professor Susumu Tonegawa, RIKEN-MIT Center at the Picower Institute, MIT, USA

Abstract

An important question in neuroscience is how a distinct memory is formed and stored in the brain. Recent studies conducted with cell ablation techniques suggest that defined populations of neurons carry a specific memory trace, or engram. However, these provide “loss of function” evidence. “The final test of any hypothesis concerning memory engrams must be a mimicry experiment in which apparent memory is manifested artificially without the usual requirement for sensory information…” (Martin and Morris, 2002). To this end, we have shown that in mice, the optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behavior in the context not used for conditioning. These data combined with those from various control experiments demonstrated that a sparse but specific ensemble of hippocampal neurons bear the engram of a specific memory, and its activation is sufficient for the recall of that memory.

While memories are usually good guides for behaviors, they can also be quite unreliable and have serious consequences in legal settings. However, the lack of relevant animal models has largely hindered our understanding of false memory formation. The development of the technology to identify and activate memory engram-bearing cells created a way to investigate neural mechanisms underlying false memories. Specifically, we hypothesized that a false memory could be generated by an association of an internally activated memory of a previous experience with a concurrently delivered external stimulus of high valence. We found such a false memory is indeed formed in mouse when the contextual engram formed previously is artificially activated subsequently by optogenetic stimulation while the footshock is delivered in a context that is distinct of the original context.

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Modular organization of the grid map

Professor Edvard Moser, NTNU, Norway

Abstract

The medial entorhinal cortex (MEC) is part of the brain’s circuit for dynamic representation of self-location. The metric of this representation is provided by grid cells, cells with spatial firing fields that tile environments in a periodic hexagonal pattern. Limited anatomical sampling has obscured whether the grid system operates as a unified system or a conglomerate of independent modules. Based on recordings from up to 186 grid cells in individual rats, we were able to show that grid cells cluster into a small number of layer-spanning anatomically-overlapping modules with distinct scale, orientation, asymmetry, and theta-frequency modulation. Although modules with small grid scales are located more dorsally than modules with larger scales, the modules exhibit considerable anatomical overlap, cutting across cell layers as well as widespread regions along both axes of the MEC sheet, suggesting that, within the same anatomical space, there are multiple cell groups with strong internal connectivity and weak cross-connectivity. The modules were able to respond independently to changes in the geometry of the environment. A significant scale relationship was revealed when increases in grid spacing were plotted across animals as a function of module number, with modules ranked according to their mean grid spacing. The scale ratio between successive module averages fluctuated around a constant value of 1.42, with a standard deviation of only 0.02, suggesting that grid scale follows a geometric progression rule. Similar modularity was not found in head direction cells, despite the presence of a dorsoventral gradient in directional tuning. The discrete topography of the grid-map, and the apparent autonomy of the modules, differ from the graded topography of maps for continuous variables in several sensory systems, raising the possibility that the modularity of the grid-map is a product of local self-organizing network dynamics. The lack of modules in head direction cells is consistent with the idea that grid modularity reflects the unique inhibitory network architecture of MEC layer II, where many grid cells are located, whereas the smoother organization of head direction cells may reflect the lack of such organization in layers III-VI, where most head direction cells are found.

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Session 3: Intracellular mechanisms

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Chair

Professor John O’Keefe FRS, University College London, UK

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Effects of cue conflict and cue deletion on the spatial firing patterns of place cells, grid cells and ventral medial entorhinal cortex place-like cells

Professor Robert Muller, Downstate Medical Center, USA

Abstract

In earlier work , it was seen that the firing fields of hippocampal place cells shifted their position in a systematic way when the angular distance between two distinct visual cues was changed; all fields were affected by this change, causing the map of the environment to be topologically stretched.  In parallel behavioral experiments, the same small cue conflicts led rats to change their decisions about the location of a hidden goal so that the new choices were displaced in the same fashion as the place cell fields.  We have now repeated the cue conflict study while rec ording simultaneously from place cells, dorsal medial entorhinal cortex (MEC) grid cells and ventral MEC place-like cells.  We find that the same topological distortion occurs for both MEC cell types, suggesting that the spatial signal is consistent in MEC and hippocampus.  Since the hexagon al field arrays of MEC grid cells are altered by this purely visual manipulation, it is hard to maintain that the grid cells provide a self-motion based, rigid metric for a topological hippocampal representation.

Along with the conflict experiments we also removed one cue card or the other.  In agreement with earlier work, the firing fields of place cells were hardly affected.  In contrast, the spatial firing patterns of dMEC gric cells and vMEC place-like cells underwent major changes, reminiscent of what is expected during complete remapping of hippocampal place cells.   This surprising outcome suggests either that key spatial input to the hippocampus arises in areas in addition to MEC or that the transform from MEC to the hippocampus is much more complex than previously believed.

Co-authors:  Dr Eun Young Song, Dr Steven E Fox.

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Head scans and place-field formation: Realtime formation of episodic memories?

Dr James Knierim, Johns Hopkins University, USA

Abstract

When rats explore, they intersperse epochs of forward movement with pauses in which they execute head-scanning movements, gathering information about the external environment. We investigated the relationship between this behavior and the formation of place fields in the hippocampus. We analyzed data from 30 rats running laps around a circular track. The rats’ trajectories were divided into periods of forward movement and periods of head scanning. We identified 789 occurrences of new CA1 and CA3 place fields suddenly forming or becoming markedly potentiated in the middle of a recording session. For ~25% of these place field formation/potentiation events, the rats had performed a head scan on the previous lap at the location of the future place field; moreover, the cell had fired during that head scan. This proportion was well above chance levels. We suggest that these changes to the place fields represent the incorporation of new information about the environment into the cognitive map and may serve as a neural correlate of the formation of a new memory.

Co-authors:
Joseph Monaco and Geeta Rao, Mind/Brain Institute, Johns Hopkins University, USA

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Probing mechanisms of grid cell formation

Professor Michael Häusser, University College London, UK

Abstract

Neurons in the medial entorhinal cortex exhibit a remarkable grid-like spatial pattern of spike rates that has been proposed to represent a neural code for path integration. How grid cell firing in stellate cells arises from the combination of intrinsic conductances and synaptic input is not well understood. We are attacking this problem using a combination of in vitro and in vivo experiments. Using two-photon glutamate uncaging in stellate cells in slices from medial entorhinal cortex, we are examining how their dendritic excitability may contribute to shaping the input-output function during grid cell firing. In parallel, we are making whole-cell patch-clamp recordings in mice navigating in a virtual reality environment, in order to determine the membrane potential signature of stellate cells during firing field crossings. Together, these experiments are providing crucial information for a quantitative understanding of the cellular basis of spatial navigation, as well as essential constraints for grid cell models.

Joint work with Christoph Schmidt-Hieber.

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Selection of specific preplay sequences during encoding of novel spatial experiences

Dr George Dragoi, Picower Institute for Learning and Memory at the Massachusetts Institute of Technology, USA

Abstract

The activity of ensembles of hippocampal place cells represents a hallmark of an animal’s spatial experience. The neuronal mechanisms that enable the rapid expression of novel place cell sequences are not entirely understood. Here, we report that during sleep or rest, distinct sets of hippocampal temporal sequences in the rat preplay multiple corresponding novel spatial experiences with high specificity. These findings suggest that the place cell sequence of a novel spatial experience is determined, in part, by an on-line selection of a subset of cellular firing sequences from a larger repertoire of preexisting temporal firing sequences in the hippocampal cellular assembly network which become rapidly bound to the novel experience. We estimate that for the given context the recorded hippocampal network activity has the capacity to preplay an extended repertoire of at least fifteen future spatial experiences of similar distinctiveness and complexity.

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Structural determinants of the grid representation in the rodent medial entorhinal cortex

Professor Michael Brecht, Humboldt University, Germany

Abstract

Extracellular recordings have provided detailed phenomenology of spatial discharge patterns (place cells, grid cells, head direction cells) in the rodent brain. At the same time we know very little about the underlying microcircuits because extracellular recordings do not identify to recorded cellular elements. We devised methods that allow
the identification of neurons in freely moving animals. We reference cells relative to the patchy architecture of layer 2 in medial entorhinal cortex. Anatomical analysis reveals that calbindin-positive pyramidal neurons layer 2 in medial entorhinal cortex are arranged in a regular and often hexonal grid. Across animals this grid of patches shows a consistent alignment to the parasubiculum and the layer 1 axons also run along a grid axis. In my talk I will discuss what identification of neurons and of this anatomical grid tell us about the origin of metric neural representations of space.

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Session 4: Codes

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Chair

Professor Neil Burgess, University College London, UK

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Grid cells in novelty, uncertainty and attractor dynamics

Dr Caswell Barry, University College London, UK

Abstract

The hippocampal formation is necessary for the creation and retrieval of spatial and episodic memories. Damage to the hippocampus and neighbouring structures leads to dense amnesia as well as severe impairments in the ability to recognise, imagine and navigate through space. Electrophysiological recordings made from animals and humans have revealed some of the neural mechanisms that support these functions. Place cells, neurons with spatially modulated firing, have been presented as a central component of the network underpinning mnemonic cognition. More recently grid cells were discovered in the entorhinal cortex of rats. The strikingly regular activity pattern exhibited by these cells has attracted considerable attention and speculation from experimental and computational communities: implicating grids as part of the neural machinery responsible for maintaining self-location and also for navigation. However, fundamental questions remain. In particular it is unclear how memory formation and retrieval are triggered.

In this presentation I will describe experiments using single unit recordings in rodents as well as computational modeling. I will show that the grid cell system is more dynamic than initial observations suggested; the spatial firing of these cells being able to change scale in response to environmental conditions. I will argue that expansion of the grid-firing pattern in novel environments facilitates the formation of new memories. I will also show that co-recorded grids of the same scale maintain their relative firing locations despite changes to the scale and location of grid-firing in general. Finally I will propose a role for cholinergic signaling – associated with memory formation – in the modulation of grid scale.

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Grid cells, membrane potential resonance and theta cycle skipping in entorhinal cortex

Professor Michael Hasselmo, Boston University, USA

Abstract

Properties of grid cells (Moser and Moser, 2008) appear to correlate with properties of membrane potential resonance. Grid cells and membrane potential resonance,appear in medial but not lateral entorhinal cortex in rats (Canto and Witter, 2012). The larger spacing between grid cell firing fields in more ventral entorhinal cortex (Moser and Moser, 2008) correlates with progressively lower resonance frequency in more ventral neurons (Giocomo et al, 2007). I will present a model showing how rebound potentials associated with cellular resonance could contribute to the generation of grid cell firing fields. The model requires rhythmic input and could account for data showing loss of spatial periodicity of grid cell firing during reduction of network theta rhythm oscillations by inactivation of the medial septum (Brandon et al 2011) and data showing functional properties of entorhinal neurons that fire on alternating cycles of theta rhythm oscillations (Brandon et al, 2013). This theta cycle skipping has appeared in a number of studies (Jeffery et al, 1995). The model also shows how grid cell firing fields could arise from resonance properties in bats, though resonance in bat medial entorhinal cortex  is not in the theta frequency range (Heys et al, 2013) and bats show less continuous theta rhythmicity (Yartsev et al, 2011). This model combines and builds from elements of previous models of oscillatory interference (Burgess et al, 2007; Zilli and Hasselmo, 2010; Welday et al, 2012) and attractor dynamics (Navratilova et al, 2012). I will also discuss the potential relationship to spatial and temporal coding for episodic memory function.

  • Brandon MP, Bogaard AR, Libby CP, Connerney, MA, Gupta K, Hasselmo ME (2011) Reduction of theta rhythm dissociates grid cell spatial periodicity from directional tuning.  Science, 332: 595-599.
  • Brandon, MP, Bogaard AR, Schultheiss NW, Hasselmo ME (2013) Segregation of cortical head direction cell assemblies on alternating theta cycles. Nature Neuroscience, in press
  • Burgess N, Barry C, O'Keefe J. 2007. An oscillatory interference model of grid cell firing. Hippocampus 17:801-12.
  • Canto CB, Witter MP.(2012) Cellular properties of principal neurons in the rat entorhinal cortex. II. The medial entorhinal cortex. Hippocampus. 22:1277-99.
  • Giocomo LM, Zilli EA, Fransen E, Hasselmo ME. (2007) Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing. Science, 315:1719-22.
  • Heys JG, MacLeod KM, Moss CF, Hasselmo ME (2013) Bat and rat neurons differ in theta frequency resonance despite similar coding of space.  Science, 340: 363-367.
  • Jeffery KJ, Donnett JG, O'Keefe J. (1995) Medial septal control of theta-correlated unit firing in the entorhinal cortex of awake rats. Neuroreport 6:2166-70.
  • Moser EI, Moser MB (2008) A metric for space. Hippocampus 18: 1142-1156.
  • Navratilova Z, Giocomo LM, Fellous JM, Hasselmo ME, McNaughton BL. (2012) Phase precession and variable spatial scaling in a periodic attractor map model of medial entorhinal grid cells with realistic after-spike dynamics. Hippocampus 22:772-89.
  • Welday AC, Shlifer IG, Bloom ML, Zhang K, Blair HT. (2011) Cosine directional tuning of theta cell burst frequencies: evidence for spatial coding by oscillatory interference. J Neurosci 31:16157-76.
  • Yartsev MM, Witter MP, Ulanovsky N. (2011) Grid cells without theta oscillations in the entorhinal cortex of bats. Nature 479:103-7.
  • Zilli EA, Hasselmo ME. 2010. Coupled noisy spiking neurons as velocity-controlled oscillators in a model of grid cell spatial firing. J Neurosci 30:13850-60.

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Synchronization coding of position by theta cells: a map built from rhythms rather than rates

Professor Hugh Tad Blair, UCLA, USA

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The hippocampus as a cognitive map: Learning, attention, space, time, and oscillations

Professor Stephen Grossberg, Boston University, USA

Abstract

This talk will review a GridPlaceMap neural model showing how a hierarchy of self-organizing maps, each obeying the same laws, responds to realistic rat trajectories by learning grid cells with hexagonal grid firing fields of multiple spatial scales, and place cells with (mostly) unimodal firing fields, that fit neurophysiological and development data about these cells in juvenile rats. The hippocampal place fields represent much larger spaces than the grid cells, and can support navigational behaviors. Both types of receptive fields are learned because each self-organizing map amplifies and learns to categorize the most energetic and frequent co-occurrences of its inputs. Top-down attentional mechanisms from hippocampus to entorhinal cortex dynamically stabilize these spatial memories, and clarify data about gamma and beta oscillations during learning of place cells in novel environments.. The model explains how the dorsoventral gradient of grid cell scales can be learned by cells that respond more slowly along the gradient to their inputs, how MPO frequencies can be generated that covary with these response rates, and how medial septal inactivation can influence grid cell firing properties. Model spatial learning through medial entorhinal cortex to hippocampus seems to use mechanisms homologous to those for temporal learning through lateral entorhinal cortex to hippocampus.

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Session 5: Systems

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Cell assemblies and complex behaviour

Professor Gyorgy Buzsáki, New York University, USA

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Chair

Professor John O’Keefe FRS, University College London, UK

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Role of hippocampal inhibitory interneurons in cognitive map selection

Professor Jozsef Csicsvari, Institute of Science and Technology, Austria

Abstract

In the hippocampus, place cells might help animals to solve spatial learning tasks by preferentially representing goal locations.  Interneuron circuits may sculpt the firing field of place cells and they may undergo plastic changes when new place maps are formed. We have trained animals to locate hidden food rewards on a cheeseboard maze, which led to the formation of new place maps, which incorporated the location of the new reward locations.  The newly-formed maps were dominantly present at later stages of learning only, while alternated with old maps at earlier stages.  Some CA1 interneurons developed associations with the newly-formed maps through selectively increasing or decreasing their firing rate with these maps. In addition, we have identified pyramidal interneuron pairs in which cross-correlation analysis suggested monosynaptic connections, and in these pairs, spike transmission probability was measured to estimate their connection strength. Changes in the connection weight between these pairs took place during the learning only and mirrored the firing associations of interneurons to the pyramidal assemblies. These results suggest that spatial learning is associated with inhibitory circuit modifications in the hippocampus that might assist in the segregation of competing pyramidal cell assembly patterns in space and time.

Coauthor:
David Dupret,  MRC Anatomical Neuropharmacology Unit, UK

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Sequential event memory formation and reactivation in the hippocampus and beyond

Professor Matthew Wilson, MIT, USA

Abstract

By introducing arrays of microelectrodes into hippocampal, neocortical, and subcortical areas of freely behaving rodents, we have characterized the detailed structure and content of memory patterns across ensembles of individual neurons as they are formed during spatial behavior, and reactivated during quiet wakefulness, and sleep.  I will review our established work on hippocampal memory formation and reactivation, and discuss more recent studies examining the involvement of brain areas beyond the hippocampus.  I will also describe recent results demonstrating the ability to influence dream content with implications for directed memory processing during sleep.

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Spatial and temporal segmentation of pyramidal cell populations by GABAergic interneurons in the hippocampus

Professor Peter Somogyi FRS, University of Oxford, UK

Abstract

During spatial navigation, or the offline replay of spatial representations, pyramidal cell firing is rhythmic and phase-related to the local field potential in the theta, gamma and sharp wave related ripple (SWR) frequency ranges. The rhythmic firing of GABAergic interneurons in the hippocampus contributes to the synchronization of neuronal activity. Interneurons innervating specific postsynaptic domains selectively discharge phase-locked to network oscillations in a cell type specific manner. We compare the cellular network dynamics of the same type of interneuron in the CA1 and CA3 areas, recorded with or without anaesthesia. All parts of pyramidal cells, except the axon initial segment, receive GABA from multiple interneuron types, each with distinct firing dynamics. Parvalbumin-expressing basket cells fire phase locked to field theta and gamma activity in both CA1 and CA3, and also strongly increase firing during SWRs, as do dendrite-innervating bistratified cells in CA1. The axon initial segment is exclusively innervated by axo-axonic cells, which preferentially fire after the peak of pyramidal layer theta when pyramidal cells are least active. Axo-axonic cells are inhibited during SWRs in both CA1 and CA3, when pyramidal cells fire most. This inverse correlation demonstrates the key inhibitory role of axo-axonic cells. The evolution of domain-specific GABAergic innervation was probably driven by the need of coordinating multiple glutamatergic inputs to pyramidal cells through temporally-distinct GABAergic interneurons, which independently change firing during different network states.

Coauthors:
Linda Katona, Thomas Klausberger, Bálint Lasztóczi and Tim Viney

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Session 6: Cognition

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Chair

Dr Tom Hartley, University of York, UK

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fMRI studies of landmark-based navigation

Professor Russell Epstein, University of Pennsylvania, USA

Abstract

Landmarks are entities that are useful for navigation because they are fixed in space. They come in a variety of forms, including single discrete objects (such as a building or statue) and extended topographical features (such as a valley, ridge, or the arrangement of buildings at an intersection). In a series of studies, we used functional magnetic resonance imaging (fMRI) to investigate how landmarks and spatial information obtained from landmarks are represented in the human brain. Results to date indicate that: (i) the posterior parahippocampal/anterior lingual region codes landmark identity and may be critical for distinguishing between landmarks based on their appearance and/or geometry; (ii) the retrosplenial/medial parietal region and presubiculum generalize beyond the landmark itself to represent the location (or “place”) implied by a landmark; (iii) the hippocampus encodes distances between landmarks, consistent with the idea that it represents locations in terms of their spatial coordinates on a cognitive map. These results shed light on how landmark-based navigation is implemented in the human brain and show that fMRI can be used to obtain information about visual and spatial representations that complements and extends the information obtained from neurophysiological recordings.

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Neural mechanisms of spatial cognition in rodents and humans

Professor Neil Burgess, University College London, UK

Abstract

Much has been inferred from neuroscientific and behavioural data regarding the various mechanisms underlying spatial cognition. Here I focus on computational models linking neuronal firing patterns to behaviour, and their interactions with experimental data via the formulation of testable predictions. Place cell representations of self-location are modelled as a combination of environmental inputs and path integration, focussing on the roles of environmental boundaries for the former and movement-related theta rhythmicity and grid cell firing for the latter. Predictions are made, and tested, regarding theta rhythmicity, novelty and remapping. A neural and systems level model of retrieval and imagery for spatial scenes is reviewed and the implications of grid-like representations in humans are discussed.

Co-presented by Dr Caswell Barry, University College London, UK

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The electrophysiology of human spatial navigation and memory

Dr Joshua Jacobs, Drexel University, USA

Abstract

I will present my recent research on the neuronal basis of human spatial navigation.  For this work, I worked with epilepsy patients that had electrodes surgically implanted in their medial temporal lobe throughout a ~1-3 week hospital stay.  During free time between clinical procedures, patients performed a virtual-reality navigation task.  By comparing  simultaneous recordings of neuronal spiking with their behavior in the task, it revealed the neural signals that underlie human spatial representations.  First, we identified neurons that encode the current spatial location.  This included "place" cells, which represent individual locations, and "grid cells," which activate at multiple locations in each environment that are arranged in a repeating triangular pattern.  We also identified entorhinal path cells, which encoded the direction of movement in the environment in a boundary-linked manner.  Finally, we probed the link between spatial navigation and memory, by testing whether the neuronal representations that appear during navigation are utilized similarly outside of movement.  Here we found that when a person retrieved navigation events, their brain actively reinstated the neuronal representation of the spatial location where that event occurred.

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Space in the brain: cells, circuits, codes and cognition Kavli Royal Society Centre, Chicheley Hall Newport Pagnell Buckinghamshire MK16 9JJ