Long-term stability of the hippocampal neural code as a substrate for episodic memory

The hippocampus supports the initial formation and recall of episodic memories, as well as the consolidation of short-term into long-term memories. The ability of hippocampal neurons to rapidly change their connection strengths during learning and maintain these changes over long time-scales may provide a mechanism supporting memory. However, little evidence currently exists concerning the long-term stability of information contained in hippocampal neuronal activity, likely due to limitations in recording extracellular activity in vivo from the same neurons across days. In this thesis I employ calcium imaging in freely moving mice to longitudinally track the activity of large ensembles of hippocampal neurons. Using this technology, I explore the proposal that long-term stability of hippocampal information provides a substrate for episodic memory in three different ways. First, I tested the hypothesis that hippocampal activity should remain stable across days in the absence of learning. I found that place cells – hippocampal neurons containing information about a mouse’s position – maintain a coherent map relative to each other across long time-scales but exhibit instability in how they anchor to the external world. Furthermore, I found that coherent maps were frequently used to represent a different environment and incorporated learning via changes in a subset of neurons. Next, I examined how learning a spatial alternation task impacts neuron stability. I found that splitter neurons whose activity patterns reflected an animal’s future or past trajectory emerged relatively slowly when compared to place cells. However, splitter neurons remained more consistently active and relayed more consistent spatial information across days than did place cells, suggesting that the utility of information provided by a neuron influences its long term stability. Last, I investigated how protein synthesis, known to be necessary for long-term maintenance of changes in hippocampal neuron connection strengths and for proper memory consolidation, influences their activity patterns across days. I found that along with blocking memory consolidation, inhibiting protein synthesis induced a profound, long-lasting decrease in neuronal activity up to two days later. These results combined demonstrate the importance of rapid, lasting changes in the hippocampal neuronal code to supporting long-term memory

29th Annual Computational Neuroscience Meeting: CNS*2020

Meeting abstracts This publication was funded by OCNS. The Supplement Editors declare that they have no competing interests. Virtual | 18-22 July 202

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201

Unsupervised space-time learning in primary visual cortex

The mammalian visual system is an incredibly complex computation device, capable of performing the various tasks of seeing: navigation, pattern and object recognition, motor coordination, trajectory extrapolation, among others. Decades of research has shown that experience-dependent plasticity of cortical circuitry underlies the impressive ability to rapidly learn many of these tasks and to adjust as required. One particular thread of investigation has focused on unsupervised learning, wherein changes to the visual environment lead to corresponding changes in cortical circuits. The most prominent example of unsupervised learning is ocular dominance plasticity, caused by visual deprivation to one eye and leading to a dramatic re-wiring of cortex. Other examples tend to make more subtle changes to the visual environment through passive exposure to novel visual stimuli. Here, we use one such unsupervised paradigm, sequence learning, to study experience-dependent plasticity in the mouse visual system. Through a combination of theory and experiment, we argue that the mammalian visual system is an unsupervised learning device. Beginning with a mathematical exploration of unsupervised learning in biology, engineering, and machine learning, we seek a more precise expression of our fundamental hypothesis. We draw connections between information theory, efficient coding, and common unsupervised learning algorithms such as Hebbian plasticity and principal component analysis. Efficient coding suggests a simple rule for transmitting information in the nervous system: use more spikes to encode unexpected information, and fewer spikes to encode expected information. Therefore, expectation violations ought to produce prediction errors, or brief periods of heightened firing when an unexpected event occurs. Meanwhile, modern unsupervised learning algorithms show how such expectations can be learned. Next, we review data from decades of visual neuroscience research, highlighting the computational principles and synaptic plasticity processes that support biological learning and seeing. By tracking the flow of visual information from the retina to thalamus and primary visual cortex, we discuss how the principle of efficient coding is evident in neural activity. One common example is predictive coding in the retina, where ganglion cells with canonical center-surround receptive fields compute a prediction error, sending spikes to the central nervous system only in response to locally-unpredictable visual stimuli. This behavior can be learned through simple Hebbian plasticity mechanisms. Similar models explain much of the activity of neurons in primary visual cortex, but we also discuss ways in which the theory fails to capture the rich biological complexity. Finally, we present novel experimental results from physiological investigations of the mouse primary visual cortex. We trained mice by passively exposing them to complex spatiotemporal patterns of light: rapidly-flashed sequences of images. We find evidence that visual cortex learns these sequences in a manner consistent with efficient coding, such that unexpected stimuli tend to elicit more firing than expected ones. Overall, we observe dramatic changes in evoked neural activity across days of passive exposure. Neural responses to the first, unexpected sequence element increase with days of training while responses at other, expected time points either decrease or stay the same. Furthermore, substituting an unexpected element for an expected one or omitting an expected element both cause brief bursts of increased firing. Our results therefore provide evidence for unsupervised learning and efficient coding in the mouse visual system, especially because unexpected events drive prediction errors. Overall, our analysis suggests novel experiments, which could be performed in the near future, and provides a useful framework to understand visual perception and learning

The Mind as a Predictive Modelling Engine: Generative Models, Structural Similarity, and Mental Representation

I outline and defend a theory of mental representation based on three ideas that I extract from the work of the mid-twentieth century philosopher, psychologist, and cybernetician Kenneth Craik: first, an account of mental representation in terms of idealised models that capitalize on structural similarity to their targets; second, an appreciation of prediction as the core function of such models; and third, a regulatory understanding of brain function. I clarify and elaborate on each of these ideas, relate them to contemporary advances in neuroscience and machine learning, and favourably contrast a predictive model-based theory of mental representation with other prominent accounts of the nature, importance, and functions of mental representations in cognitive science and philosophy.This work was supported by the Arts and Humanities Research Council

Auf einem menschlichen Gehörmodell basierende Elektrodenstimulationsstrategie für Cochleaimplantate

Cochleaimplantate (CI), verbunden mit einer professionellen Rehabilitation, haben mehreren hunderttausenden Hörgeschädigten die verbale Kommunikation wieder ermöglicht. Betrachtet man jedoch die Rehabilitationserfolge, so haben CI-Systeme inzwischen ihre Grenzen erreicht. Die Tatsache, dass die meisten CI-Träger nicht in der Lage sind, Musik zu genießen oder einer Konversation in geräuschvoller Umgebung zu folgen, zeigt, dass es noch Raum für Verbesserungen gibt.Diese Dissertation stellt die neue CI-Signalverarbeitungsstrategie Stimulation based on Auditory Modeling (SAM) vor, die vollständig auf einem Computermodell des menschlichen peripheren Hörsystems beruht.Im Rahmen der vorliegenden Arbeit wurde die SAM Strategie dreifach evaluiert: mit vereinfachten Wahrnehmungsmodellen von CI-Nutzern, mit fünf CI-Nutzern, und mit 27 Normalhörenden mittels eines akustischen Modells der CI-Wahrnehmung. Die Evaluationsergebnisse wurden stets mit Ergebnissen, die durch die Verwendung der Advanced Combination Encoder (ACE) Strategie ermittelt wurden, verglichen. ACE stellt die zurzeit verbreitetste Strategie dar. Erste Simulationen zeigten, dass die Sprachverständlichkeit mit SAM genauso gut wie mit ACE ist. Weiterhin lieferte SAM genauere binaurale Merkmale, was potentiell zu einer Verbesserung der Schallquellenlokalisierungfähigkeit führen kann. Die Simulationen zeigten ebenfalls einen erhöhten Anteil an zeitlichen Pitchinformationen, welche von SAM bereitgestellt wurden. Die Ergebnisse der nachfolgenden Pilotstudie mit fünf CI-Nutzern zeigten mehrere Vorteile von SAM auf. Erstens war eine signifikante Verbesserung der Tonhöhenunterscheidung bei Sinustönen und gesungenen Vokalen zu erkennen. Zweitens bestätigten CI-Nutzer, die kontralateral mit einem Hörgerät versorgt waren, eine natürlicheren Klangeindruck. Als ein sehr bedeutender Vorteil stellte sich drittens heraus, dass sich alle Testpersonen in sehr kurzer Zeit (ca. 10 bis 30 Minuten) an SAM gewöhnen konnten. Dies ist besonders wichtig, da typischerweise Wochen oder Monate nötig sind. Tests mit Normalhörenden lieferten weitere Nachweise für die verbesserte Tonhöhenunterscheidung mit SAM.Obwohl SAM noch keine marktreife Alternative ist, versucht sie den Weg für zukünftige Strategien, die auf Gehörmodellen beruhen, zu ebnen und ist somit ein erfolgversprechender Kandidat für weitere Forschungsarbeiten.Cochlear implants (CIs) combined with professional rehabilitation have enabled several hundreds of thousands of hearing-impaired individuals to re-enter the world of verbal communication. Though very successful, current CI systems seem to have reached their peak potential. The fact that most recipients claim not to enjoy listening to music and are not capable of carrying on a conversation in noisy or reverberative environments shows that there is still room for improvement.This dissertation presents a new cochlear implant signal processing strategy called Stimulation based on Auditory Modeling (SAM), which is completely based on a computational model of the human peripheral auditory system.SAM has been evaluated through simplified models of CI listeners, with five cochlear implant users, and with 27 normal-hearing subjects using an acoustic model of CI perception. Results have always been compared to those acquired using Advanced Combination Encoder (ACE), which is today’s most prevalent CI strategy. First simulations showed that speech intelligibility of CI users fitted with SAM should be just as good as that of CI listeners fitted with ACE. Furthermore, it has been shown that SAM provides more accurate binaural cues, which can potentially enhance the sound source localization ability of bilaterally fitted implantees. Simulations have also revealed an increased amount of temporal pitch information provided by SAM. The subsequent pilot study, which ran smoothly, revealed several benefits of using SAM. First, there was a significant improvement in pitch discrimination of pure tones and sung vowels. Second, CI users fitted with a contralateral hearing aid reported a more natural sound of both speech and music. Third, all subjects were accustomed to SAM in a very short period of time (in the order of 10 to 30 minutes), which is particularly important given that a successful CI strategy change typically takes weeks to months. An additional test with 27 normal-hearing listeners using an acoustic model of CI perception delivered further evidence for improved pitch discrimination ability with SAM as compared to ACE.Although SAM is not yet a market-ready alternative, it strives to pave the way for future strategies based on auditory models and it is a promising candidate for further research and investigation

Recent Advances in Multi Robot Systems

To design a team of robots which is able to perform given tasks is a great concern of many members of robotics community. There are many problems left to be solved in order to have the fully functional robot team. Robotics community is trying hard to solve such problems (navigation, task allocation, communication, adaptation, control, ...). This book represents the contributions of the top researchers in this field and will serve as a valuable tool for professionals in this interdisciplinary field. It is focused on the challenging issues of team architectures, vehicle learning and adaptation, heterogeneous group control and cooperation, task selection, dynamic autonomy, mixed initiative, and human and robot team interaction. The book consists of 16 chapters introducing both basic research and advanced developments. Topics covered include kinematics, dynamic analysis, accuracy, optimization design, modelling, simulation and control of multi robot systems

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40