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

• Dr Tom Hartley, University of York, UK

Biography

Tom Hartley is a cognitive neuroscientist and lecturer in the Department of Psychology at the University of York. His PhD at UCL developed a model of serial order in verbal short-term memory. Several postdoctoral positions at UCL culminated in a long spell at the Institute of Cognitive Neuroscience working with Neil Burgess and John O’Keefe during which he combined neuroimaging, neuropsychological and behavioural investigations of spatial cognition in humans with computational modelling of neural representations and behaviour. His current research investigates the brain basis of individual differences in spatial memory and the parts played by ventral visual cortex and retrosplenial cortex in scene processing and spatial representation.

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

Biography

John O’Keefe FRS is Professor of Cognitive Neuroscience at University College London where he works in the Department of Cell and Developmental Biology and is currently Interim Director of the Sainsbury Wellcome Centre for Neural Circuits and Behaviour.

O’Keefe is interested in the role of the hippocampal formation in spatial memory and navigation. Using extracellular recording in behaving rats, O’Keefe discovered that hippocampal pyramidal cells respond selectively to an animal’s spatial location.  The discovery of  ‘place cells’ suggested that this part of the brain might function as a cognitive map, a notion developed extensively by O'Keefe and Nadel in a book published in 1978 (www.cognitive map.net). In 1993, he and Recce reported that the hippocampal code for location was based on the timing, as well as the rate, of place cell activity. The timing code is referenced to the 7-11 Hz theta rhythm seen in the hippocampal LFP as the animal moves around an environment.  O’Keefe suggested this phase precession effect might be due to interference wavelets produced by the summation of 2 theta- like oscillators of differing frequencies. With Burgess and Barry, he has extended this model to 2 spatial dimensions and shown how this extended model accounts for the firing fields of entorhinal cortical grid cells. He has recently turned his attention to the amygdala and its role in active memory for ethologically significant stimuli.

• Professor Neil Burgess, University College London, UK

Biography

Neil Burgess is Professor of cognitive and computational neuroscience and a Wellcome Trust Principal Research Fellow at the UCL Institute of Cognitive Neuroscience. His laboratory investigates the neural mechanisms of memory using a combination of methods including computational modeling, human neuropsychology and functional neuroimaging and single unit recordings in freely moving rodents. His main goal is to understand how the actions of networks of neurons in our brains allow us to remember events and the spatial locations where they occurred. After studying Maths and Physics at UCL he did a PhD in Theoretical Physics in Manchester and a research fellowship in Rome, before returning to UCL funded by a Royal Society University Research Fellowship, and a Medical Research Council Senior Research Fellowship.

• Dr Colin Lever, University of Durham, UK

Biography

Following undergraduate and Master’s degrees at Oxford University then UCL, Colin did his PhD in John O’Keefe’s laboratory in UCL, working on learning and memory in hippocampal place cells. He did further postdoctoral work with John O’Keefe and Neil Burgess, and spent a few months in Bob and Caroline Blanchard’s lab in the US on a Bogue Fellowship in 2005. He set up his own lab in Leeds University in 2005, and moved to Durham University in 2011, where he is Senior Lecturer in Cognitive Neuroscience in the Psychology Department. Colin’s work focuses on spatial cells, memory mechanisms, and the theta oscillation. Colin gratefully acknowledges funding for the research presented at this meeting (talk, poster) from the BBSRC and Royal Society.

• Dr Tom Hartley, University of York, UK

Biography

Tom Hartley is a cognitive neuroscientist and lecturer in the Department of Psychology at the University of York. His PhD at UCL developed a model of serial order in verbal short-term memory. Several postdoctoral positions at UCL culminated in a long spell at the Institute of Cognitive Neuroscience working with Neil Burgess and John O’Keefe during which he combined neuroimaging, neuropsychological and behavioural investigations of spatial cognition in humans with computational modelling of neural representations and behaviour. His current research investigates the brain basis of individual differences in spatial memory and the parts played by ventral visual cortex and retrosplenial cortex in scene processing and spatial representation.

• Professor May-Britt Moser, NTNU, Norway

Biography

May-Britt Moser is a Professor of Neuroscience and Co-Director of the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology in Trondheim. She is interested in the neural basis of spatial location and spatial specifically and cognition more generally. Her work, conducted with Edvard Moser as a long-term collaborator, includes the discovery of grid cells in the entorhinal cortex, which provides the first clues to a neural mechanism for the metric of spatial mapping. Subsequent to this discovery the Mosers have identified additional space-representing cell types in the entorhinal cortex and they are beginning to unravel how the neural microcircuit is organized. May-Britt Moser received her initial training at the University of Oslo under the supervision of Dr. Per Andersen on the structural basis of hippocampal memory. In 1995-96, she worked as a post-doc with Richard Morris on septotemporal differentiation within the hippocampus and the role of long-term potentiation in spatial memory. In 1996, she spent one month with John O’Keefe to learn tetrode recording in the hippocampus. May-Britt Moser accepted an associate professorship at the Norwegian University of Science and Technology in August 1996. She became a full professor at the same institution in 2000. In 2002 she became Founding Co-Director of the Centre for the Biology of Memory, a Research Council-funded Centre of Excellence. In 2013, she was appointed Founding Director of the Centre for Neural Computation at the same institution.

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.

• Professor Kate Jeffery, University College London, UK

Biography

Kate Jeffery is professor of behavioural neuroscience at University College London (UCL). After graduating in medicine from the University of Otago, New Zealand, she embarked on a research career in behavioural physiology, training with Cliff Abraham (Otago), Richard Morris (University of Edinburgh), and John O’Keefe (UCL). In 1999 she joined the psychology faculty at UCL, where she is now head of its Cognitive, Perceptual and Brain Sciences research department.  She is also co-director of the behavioural physiology instrumentation company Axona Ltd, which she co-founded with her husband Jim Donnett.Her research interests lie in how neurons in the navigation system integrate sensory information in order to form higher order, cognitive representations.

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.

• Professor Nachum Ulanovsky, Weizmann Institute, Israel

Biography

After undergraduate studies in Physics and a PhD in Neural Computation – where he studied electrophysiological correlates of auditory memory – Dr Nachum Ulanovsky became interested in more general questions of brain and memory, and spatial memory in particular.  The work in his 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.  Studies in his lab include recordings of 2-D spatial cells in the hippocampal formation of bats (place cells, grid cells, and head-direction cells), as well as more recent work on 3-D spatial cells.  Dr Ulanovsky has been interested also in relating spatial behaviors in the lab to natural behaviors in the wild, which led him to study the behaviors and navigational strategies of fruit bats in the wild, using micro-GPS devices; these studies revealed outstanding navigational abilities, and provided evidence for a large-scale cognitive map in bats.  The long-term goal of Dr Ulanovsky's lab is to use the bat in order to provide new insights on general questions of Space in the Brain.

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.

• Dr Julija Krupic, University College London, UK

Biography

Dr Julija Krupic is a postdoc in Professor O’Keefe’s lab at University College London. She did her undergraduate studies in Physics in Vilnius University in Lithuania, followed by a Masters Degree at Imperial College London supervised by Dr Simon Schultz where she developed spatial independent component analysis techniques for automatic neural identification in cerebellum and somatosensory cortex. She then joined Professor O’Keefe’s lab where she did her PhD studies co-supervised by Professor Burgess studying the mechanism of grid cell pattern formation. She has shown that, in addition to grids, there are other spatially periodic cells in the parahippocampal formation which do not show hexagonal symmetry and have suggested that grid cells form a subset of a larger continuum of locational cells whose firing properties can be described as a weighted sum of a small number (from 1 to 4) of periodic band-like inputs. Currently her main research interest is the mechanism of grid cell pattern formation and how grid cells contribute to place cell firing.

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.

• Dr Colin Lever, University of Durham, UK

Biography

Following undergraduate and Master’s degrees at Oxford University then UCL, Colin did his PhD in John O’Keefe’s laboratory in UCL, working on learning and memory in hippocampal place cells. He did further postdoctoral work with John O’Keefe and Neil Burgess, and spent a few months in Bob and Caroline Blanchard’s lab in the US on a Bogue Fellowship in 2005. He set up his own lab in Leeds University in 2005, and moved to Durham University in 2011, where he is Senior Lecturer in Cognitive Neuroscience in the Psychology Department. Colin’s work focuses on spatial cells, memory mechanisms, and the theta oscillation. Colin gratefully acknowledges funding for the research presented at this meeting (talk, poster) from the BBSRC and Royal Society.

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.

• Dr Colin Lever, University of Durham, UK

Biography

Following undergraduate and Master’s degrees at Oxford University then UCL, Colin did his PhD in John O’Keefe’s laboratory in UCL, working on learning and memory in hippocampal place cells. He did further postdoctoral work with John O’Keefe and Neil Burgess, and spent a few months in Bob and Caroline Blanchard’s lab in the US on a Bogue Fellowship in 2005. He set up his own lab in Leeds University in 2005, and moved to Durham University in 2011, where he is Senior Lecturer in Cognitive Neuroscience in the Psychology Department. Colin’s work focuses on spatial cells, memory mechanisms, and the theta oscillation. Colin gratefully acknowledges funding for the research presented at this meeting (talk, poster) from the BBSRC and Royal Society.

• Professor Menno Witter, NTNU, Norway

Biography

Menno Witter was born in The Netherlands, and his career in functional neuroanatomy started at the VU University in Amsterdam where he obtained his PhD in 1985. He has published influential and classic papers on the anatomy of the cortico-hippocampal system, in which he promoted the concept of functional differentiation within the hippocampus and parahippocampus, an issue which is at the heart of main stream research in the hippocampal field. In 2007, he joined the Kavli Institute for Systems Neuroscience at the Norwegian University for Science and Technology (NTNU) in Trondheim, where he contributed to the discovery of grid cells in the medial entorhinal cortex. His current research, using advanced combinations of electrophysiological and neuroanatomical techniques, focusses on the intrinsic architecture of the lateral and medial entorhinal cortex. In a recent publication he reported that the local circuit connecting putative grid cells is governed by inhibitory connectivity.

He is director of the recently established Norwegian Research School for Neuroscience and elected member of The Royal Norwegian Society of Sciences and Letters (Det Kongelige Norske Videnskabers Selskab) and of The Norwegian Academy of Science (Det Norske Vitensskaps-Akademi).

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

• Professor Edvard Moser, NTNU, Norway

Biography

Edvard Moser is a Professor of Neuroscience and Director of the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology in Trondheim. He is interested in how spatial location and spatial memory are computed in the brain. His work, conducted with May-Britt Moser as a long-term collaborator, includes the discovery of grid cells in the entorhinal cortex, which provides the first clues to a neural mechanism for the metric of spatial mapping. Subsequent to this discovery the Mosers have identified additional space-representing cell types in the entorhinal cortex and they are beginning to unravel how the neural microcircuit is organized. Edvard Moser received his initial training at the University of Oslo under the supervision of Dr Per Andersen on mechanisms of memory formation in the hippocampus in freely-moving animals. In 1995-96, he worked as a post-doc with Richard Morris on the role of long-term potentiation in hippocampal memory. In 1996, he spent three months with John O’Keefe to learn tetrode recording in the hippocampus. Edvard Moser accepted an associate professorship at the Norwegian University of Science and Technology in August 1996. He became a full professor at the same institution in 1998. In 2002 he became the Founding Director of the Centre for the Biology of Memory, a Research Council-funded Centre of Excellence. In 2007 the Centre became a Kavli Institute.

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.

• Dr Tom Wills, University College London, UK

Biography

Dr Tom Wills completed his PhD thesis in the laboratory of John O’Keefe, investigating the way in which Place Cells in the hippocampal formation encode representations of different locations, and how this may act as a mechanism for episodic memory. During his post-doctoral research, he conducted some of the first experiments looking at the early post-natal development of the hippocampal neural representation of space. He currently holds a Royal Society University Research Fellowship, at University College London, and his research remains focused on understanding the ontogeny of neural circuits coding for space in the hippocampal formation.

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.

• Professor Susumu Tonegawa, Riken-MIT, USA

Biography

Susumu Tonegawa received his PhD from UCSD. He then undertook postdoctoral work at the Salk Institute in San Diego, before working at the Basel Institute for Immunology in Basel, Switzerland, where he performed his landmark immunology experiments. Tonegawa won the Nobel Prize for Physiology or Medicine in 1987 for “his discovery of the genetic principle for generation of antibody diversity”. He has since continued to make important contributions but in an entirely different field: neuroscience. Using advanced techniques of gene manipulation, Tonegawa is now unraveling the molecular, cellular and neural circuit mechanisms that underlie learning and memory. His studies have broad implications for psychiatric and neurologic diseases. Tonegawa is currently Picower Professor of Biology and Neuroscience at the Massachusetts Institute of Technology (MIT) and the Director of the RIKEN-MIT Center for Neural Circuit Genetics at MIT as well as the Director of RIKEN Brain Science Institute.

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.

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

Biography

John O’Keefe FRS is Professor of Cognitive Neuroscience at University College London where he works in the Department of Cell and Developmental Biology and is currently Interim Director of the Sainsbury Wellcome Centre for Neural Circuits and Behaviour.

O’Keefe is interested in the role of the hippocampal formation in spatial memory and navigation. Using extracellular recording in behaving rats, O’Keefe discovered that hippocampal pyramidal cells respond selectively to an animal’s spatial location. The discovery of ‘place cells’ suggested that this part of the brain might function as a cognitive map, a notion developed extensively by O'Keefe and Nadel in a book published in 1978 (www.cognitive map.net). In 1993, he and Recce reported that the hippocampal code for location was based on the timing, as well as the rate, of place cell activity. The timing code is referenced to the 7-11 Hz theta rhythm seen in the hippocampal LFP as the animal moves around an environment. O’Keefe suggested this phase precession effect might be due to interference wavelets produced by the summation of 2 theta- like oscillators of differing frequencies. With Burgess and Barry, he has extended this model to 2 spatial dimensions and shown how this extended model accounts for the firing fields of entorhinal cortical grid cells. He has recently turned his attention to the amygdala and its role in active memory for ethologically significant stimuli.

• Professor Michael Häusser, University College London, UK

Biography

Michael Häusser did his PhD at Oxford University under the supervision of Julian Jack. He subsequently worked with Bert Sakmann at the Max-Planck-Institute for Medical Research in Heidelberg and with Philippe Ascher at the Ecole Normale Superieure in Paris. He established his own lab at UCL in 1997 with the support of a Wellcome Trust Career Development Fellowship, and in 2001 became Professor of Neuroscience and a Wellcome Senior Research Fellow. He recently was awarded an ERC Advanced Grant and a Principal Research Fellowship from the Wellcome Trust.

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.

• Dr James Knierim, Johns Hopkins University, USA

Biography

James Knierim received a PhD in Neurobiology from Caltech in 1991.  His dissertation research with David Van Essen entailed recordings from the primary visual cortex of alert macaque monkeys viewing visual texture patterns.  He did postdoctoral research with Bruce McNaughton on hippocampal place cells and thalamic head direction cells.  In 1998 he became Assistant Professor in the Dept. of Neurobiology & Anatomy at the University of Texas Medical School at Houston.  In 2009 he moved to the Krieger Mind/Brain Institute of Johns Hopkins University, where he is now a Professor of Neuroscience.  His research investigates the interactions among the various input and output regions of the hippocampus, including the entorhinal cortex, the dentate gyrus, and the CA3 and CA1 regions.

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

• Professor Robert Muller, Downstate Medical Center, USA

Biography

Bob Muller got his PhD at the Albert Einstein College of Medicine in Biophysics, studying the molecular mechanisms of channel formation underlying an antibiotic-induced voltage-dependent conductance in thin lipid membranes.  He continued this line of research at Downstate Medical Center until, during a visit to Jim Ranck’s lab down the hall he saw a place cell being recorded by John Kubie, an event that caused him to immediately ask if he could get involved with Jim and John’s work.  This collaboration resulted in a series of papers outlining many basic properties of place cells and led directly to a quantitative description of the head direction cells discovered by Jim.  In a continuing line of work, he investigated with Andre Fenton how place cells are affected by combinations of simple stimuli.   A fruitful collaborationhas continued over many years with Dr. Bruno Poucet of the University of Marseille.  In addition, he has contributed to work on the synaptic plasticity mechanisms that underlie place cell formation and stability.

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.

• Professor Michael Brecht, Humboldt University, Germany

Biography

Michael Brecht grew up in Muenster, Germany and started to study biochemistry at the University of Tuebingen. He soon became interested in animal behavior and did a one-year internship at Hubbs Sea World Research Institute, San Diego on sperm whale bioacoustics. Thus, he decided to finish in biology rather than in biochemistry. His diploma work with Bruno Preilowski and Michael Merzenich at University of California San Francisco was concerned with rat vibrissal behaviors. Subsequently he did a PhD in the lab of Wolf Singer on the role synchronization of neural activity in the superior colliculus in the control of eye movements. After his PhD he felt that we will not succeed in understanding population activity without an improved knowledge about cellular computations in vivo. He therefore joined Bert Sakmann’s lab as a postdoc to do in vivo whole-cell recordings in rat barrel cortex. From there he went first to Erasmus University, Rotterdam to become an assistant professor and then to Humboldt University, Berlin, where he became a full professor. His research group works on (1) the meaning of single neuron activity, (2) cellular mechanisms of complex somatosensory–mediated behaviors, (3) spatial representation, (4) social representations in forebrain.

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.

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

Biography

George Dragoi is Research Scientist at the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology. He is currently working in the laboratory of Dr Susumu Tonegawa. Dr Dragoi holds MD degree from the Gr. T Popa University of Medicine and Pharmacy of Iasi, Romania and PhD degree in Behavioral and Neural Science from Rutgers University where he worked in the laboratory of Dr Gyorgy Buzsaki. Dr Dragoi studies the neurophysiological basis of the organization of hippocampal neurons into cellular assemblies and their dynamic grouping during novel spatial exploration and in response to long-term potentiation. Recently, he revealed the existence of preconfigured cellular assemblies that pre-play in time the spatial sequences occurring during a future novel spatial experience. Dr Dragoi’s current research focuses on the role of neuronal activity and prior experience in cellular assembly organization and animal learning.

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.

• Professor Neil Burgess, University College London, UK

Biography

Neil Burgess is Professor of cognitive and computational neuroscience and a Wellcome Trust Principal Research Fellow at the UCL Institute of Cognitive Neuroscience. His laboratory investigates the neural mechanisms of memory using a combination of methods including computational modeling, human neuropsychology and functional neuroimaging and single unit recordings in freely moving rodents. His main goal is to understand how the actions of networks of neurons in our brains allow us to remember events and the spatial locations where they occurred. After studying Maths and Physics at UCL he did a PhD in Theoretical Physics in Manchester and a research fellowship in Rome, before returning to UCL funded by a Royal Society University Research Fellowship, and a Medical Research Council Senior Research Fellowship.

• Professor Michael Hasselmo, Boston University, USA

Biography

Michael Hasselmo is a Professor at Boston University in the Department of Psychology and the Graduate Program for Neuroscience. He is principal investigator on two NIMH R01 grants and an ONR MURI award. Research in his lab includes whole cell patch recordings to analyze intracellular dynamics in brain slice preparations of cortex, and extracellular recording of unit activity including grid cells and head direction cells. His modeling includes network level models and detailed biophysical models. Recent publications address the function of theta rhythm oscillations in generation of grid cell firing and encoding of information, building on his earlier models of the role of acetylcholine and oscillations in regulating encoding dynamics.  Michael E. Hasselmo graduated summa cum laude from Harvard College, received a Rhodes scholarship and completed a D.Phil. at Oxford University. After a post-doctoral fellowship at the California Institute of Technology, he was on the faculty at Harvard University before moving to Boston University.  He has published over 120 articles in journals including Science, Nature, Journal of Neuroscience, Hippocampus, Journal of Neurophysiology, Neuron, Trends in Cognitive Sciences and Trends in Neurosciences.

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.

• Professor Stephen Grossberg, Boston University, USA

Biography

Stephen Grossberg is Wang Professor of Cognitive and Neural Systems; Professor of Mathematics, Psychology, and Biomedical Engineering; and Director of its Center for Adaptive Systems at Boston University. He is a principal founder and current research leader in computational neuroscience, connectionist cognitive science, and neuromorphic technology. Grossberg introduced the paradigm of using nonlinear systems of differential equations to model how brain mechanisms give rise to behavioral functions. In 1957-1958, he introduced widely used equations for short-term memory (STM), or neuronal activation; medium-term memory (MTM), or activity-dependent habituation; and long-term memory (LTM), or neuronal learning. His work focuses upon how individuals adapt autonomously in real-time to unexpected environmental challenges, and includes models of vision and visual cognition; object, scene, and event recognition; audition, speech and language; development; cognitive information processing; reinforcement learning and cognitive-emotional interactions; navigation; social cognition; sensory-motor control; mental disorders; and neuromorphic technology. Grossberg founded key infrastructure of the field of neural networks, including the International Neural Network Society and the journal Neural Networks. He is a fellow of AERA, APA, APS, IEEE, INNS, MDRS, and SEP. He has published 17 books or journal special issues, over 500 research articles, and has 7 patents.

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.

• Dr Caswell Barry, University College London, UK

Biography

Dr Caswell Barry is an Excellence Fellow at UCL’s Department of Cell and Developmental Biology. Following an undergraduate degree at Oxford University he conducted his PhD with Neil Burgess at UCL. As a postdoc he continued to work with Neil and subsequently with Mike Hasselmo at Boston University. His aim is to understand how human memory for places and events is generated and maintained in the brain. Caswell’s laboratory draws on a range of methods including computational modeling, behavioral studies in humans, and single unit recording from freely moving animals. His work is published in a number of highly visible journals including Nature, Science, Nature Neuroscience and PNAS.

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.

• Professor Hugh Tad Blair, UCLA, USA

Biography

Hugh (Tad) Blair is an Associate Professor of Behavioral Neuroscience in the Psychology Department at the University of California, Los Angeles (UCLA). Before joining the UCLA faculty, he received his PhD in Behavioral Neuroscience from Yale University, where he conducted his thesis research on head-direction cells in the laboratory of Patricia Sharp. He also worked as a postdoctoral researcher in the laboratory of Joseph LeDoux at New York University’s Center for Neural Science, where he investigated neural circuits underlying fear conditioning and defensive behaviors. Currently, his laboratory’s research is focused upon investigating the role of oscillatory rhythms in neural coding, and also upon neural circuits underlying fear, anxiety, and defensive action selection.

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

Biography

John O’Keefe FRS is Professor of Cognitive Neuroscience at University College London where he works in the Department of Cell and Developmental Biology and is currently Interim Director of the Sainsbury Wellcome Centre for Neural Circuits and Behaviour.

O’Keefe is interested in the role of the hippocampal formation in spatial memory and navigation. Using extracellular recording in behaving rats, O’Keefe discovered that hippocampal pyramidal cells respond selectively to an animal’s spatial location. The discovery of ‘place cells’ suggested that this part of the brain might function as a cognitive map, a notion developed extensively by O'Keefe and Nadel in a book published in 1978 (www.cognitive map.net). In 1993, he and Recce reported that the hippocampal code for location was based on the timing, as well as the rate, of place cell activity. The timing code is referenced to the 7-11 Hz theta rhythm seen in the hippocampal LFP as the animal moves around an environment. O’Keefe suggested this phase precession effect might be due to interference wavelets produced by the summation of 2 theta- like oscillators of differing frequencies. With Burgess and Barry, he has extended this model to 2 spatial dimensions and shown how this extended model accounts for the firing fields of entorhinal cortical grid cells. He has recently turned his attention to the amygdala and its role in active memory for ethologically significant stimuli.

• Professor Peter Somogyi FRS, University of Oxford, UK

Biography

Peter Somogyi, FRS, is the director of the Medical Research Council Anatomical Neuropharmacology Unit and Professor of Neurobiology at the University of Oxford. The Unit investigates the synaptic organisation and temporal dynamics of neuronal systems in the mammalian brain. Educated as a biologist in Hungary, he has explored identified neurons in the cerebellum, thalamus, brain stem, basal ganglia and the cerebral cortex. His vision is that explanations of normal and pathological events in the brain require the simultaneous definition of the neuronal organisation in space and time, the chronocircuit. In the last decade, he has focussed on exploring the brain- and network-state dependent activity patterns of identified hippocampal neurons. With his colleagues he discovered a highly specialised spatial and molecular organisation of interneurons, which has also led to the discovery of an unexpected temporal specialisation of GABA release to distinct domains of pyramidal cells.

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

• Professor Jozsef Csicsvari, Institute of Science and Technology, Austria

Biography

Dr Jozsef Csicsvari graduated in Informatics at the Technical University of Budapest, Hungary, in 1993.  He undertook doctoral (1993-1999) and postdoctoral (1999-2002) training under the supervision of Professor Gyorgy Buzsaki at Rutgers University, USA. In 2003 he became a group leader at the MRC Anatomical Neuropharmacology Unit in Oxford. In 2010, he was awarded the title of Professor of Neuroscience at the University of Oxford. In 2011 he joint IST Austria as a Professor. His research interest has been to study oscillatory activity in the brain, and to understand the behavioural role and physiological mechanism of these oscillations in the hippocampus, in particular in mnemonic processes.

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

• Professor Matthew Wilson, MIT, USA

Biography

Professor Wilson received his BS in Electrical Engineering from Rensselaer Polytechnic Institute, his MS in Electrical Engineering from the University of Wisconsin, Madison, and his PhD. in Computation and Neural Systems from the California Institute of Technology. He joined the faculty at MIT in the Department of Brain and Cognitive Sciences in 1994 where he focused on the study of mechanisms of memory formation through the use of microelectrode arrays implanted in the brains of freely behaving rodents. By monitoring the coordinated activity of ensembles of large numbers of individual neurons during active behavior, sleep, and quiet wakefulness he identified a process of memory reactivation that reflected both the content and the temporal linkage of events that could constitute the basis of episodic memory. These events may reflect the animal equivalent of dreaming. His ongoing work has continued to study brain systems that contribute to learning, memory, spatial navigation, and decision-making and their possible involvement in neurological diseases and disorders. He has ongoing interests in the mechanisms of sleep and arousal, the relationship between memory and dreams, and applications of neuroscience in engineering and the study of intelligence. He is currently the Sherman Fairchild Professor of Neuroscience, and Associate Director of the Picower Institute for Learning and Memory at MIT.

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.

• Professor Gyorgy Buzsáki, New York University, USA

Biography

György Buzsáki is Biggs Professor of Neuroscience at New York University. His primary interests are mechanisms of memory, sleep and associated diseases. His main focus is “neural syntax”, i.e., how segmentation of neural information is organized by the numerous brain rhythms to support cognitive functions. His most influential work, the two-stage model of memory trace consolidation, demonstrates how the neocortex-mediated information during learning transiently modifies hippocampal networks, followed by reactivation and consolidation of these memory traces during sleep. With more than 300 papers published on these topics, he is among the top 150 most-cited neuroscientists. Buzsáki is a Fellow of the American Association for the Advancement of Science and the Academiae Europaeae and an honorary member of the Hungarian Academy of Sciences, and he sits on the editorial boards of several leading neuroscience journals, including Science and Neuron. He is a co-recipient of the 2011 Brain Prize.

(Book: G Buzsáki, Rhythms of the Brain, Oxford University Press, 2006)

• Dr Tom Hartley, University of York, UK

Biography

Tom Hartley is a cognitive neuroscientist and lecturer in the Department of Psychology at the University of York. His PhD at UCL developed a model of serial order in verbal short-term memory. Several postdoctoral positions at UCL culminated in a long spell at the Institute of Cognitive Neuroscience working with Neil Burgess and John O’Keefe during which he combined neuroimaging, neuropsychological and behavioural investigations of spatial cognition in humans with computational modelling of neural representations and behaviour. His current research investigates the brain basis of individual differences in spatial memory and the parts played by ventral visual cortex and retrosplenial cortex in scene processing and spatial representation.

• Professor Neil Burgess, University College London, UK

Biography

Neil Burgess is Professor of cognitive and computational neuroscience and a Wellcome Trust Principal Research Fellow at the UCL Institute of Cognitive Neuroscience. His laboratory investigates the neural mechanisms of memory using a combination of methods including computational modeling, human neuropsychology and functional neuroimaging and single unit recordings in freely moving rodents. His main goal is to understand how the actions of networks of neurons in our brains allow us to remember events and the spatial locations where they occurred. After studying Maths and Physics at UCL he did a PhD in Theoretical Physics in Manchester and a research fellowship in Rome, before returning to UCL funded by a Royal Society University Research Fellowship, and a Medical Research Council Senior Research Fellowship.

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

• Dr Joshua Jacobs, Drexel University, USA

Biography

Joshua Jacobs, PhD, directs the Cognitive Brain Dynamics Laboratory at Drexel University.  His research team studies the neural basis of human cognition with direct brain recordings from neurosurgical patients.  Jacobs is currently using this approach to study the electrophysiology of two different types of behavior: spatial cognition and working memory. His work utilizes both recordings of single-neuron spiking from microelectrodes, as well as recordings of brain oscillations from macroelectrodes.  An overarching goal of his work is to link work on human cognition with research on the neural basis of brain function in animals.

Jacobs was originally trained in Computer Science, receiving Bachelor (2001) and Masters Degrees (2002) from MIT.  He then studied Neuroscience at the University of Pennsylvania, receiving his PhD in 2008.  In 2010, he joined the faculty of Drexel University as an Assistant Professor in the School of Biomedical Engineering, Sciences, and Health systems.

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.

• Professor Russell Epstein, University of Pennsylvania, USA

Biography

Russell Epstein is Associate Professor of Psychology at the University of Pennsylvania. His research focuses on the use of brain imaging techniques to understand the neural systems involved in scene perception, place recognition, and spatial navigation in humans. He received a BA in Physics from the University of Chicago in 1991 and a PhD in Applied Mathematics with a focus on computer vision from Harvard in 1996. He subsequently did postdoctoral work with Nancy Kanwisher at MIT and John Duncan at the MRC Cognition and Brain Sciences Unit in Cambridge UK before joining the Penn faculty in 2002. His research is supported by the National Eye Institute and the National Science Foundation.

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.