Two photon interrogation of hippocampal subregions CA1 and CA3 during spatial behaviour

The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and form the neural basis of a cognitive map of space which supports these mnemonic functions. Hebb’s (1949) postulate regarding the creation of cell assemblies is seen as the pre-eminent model of learning in neural systems. Investigating changes to the hippocampal representation of space during an animal’s exploration of its environment provides an opportunity to observe Hebbian learning at the population and single cell level. When exploring new environments animals form spatial memories that are updated with experience and retrieved upon re-exposure to the same environment, but how this is achieved by different subnetworks in hippocampal CA1 and CA3, and how these circuits encode distinct memories of similar objects and events remains unclear. To test these ideas, we developed an experimental strategy and detailed protocols for simultaneously recording from CA1 and CA3 populations with 2P imaging. We also developed a novel all-optical protocol to simultaneously activate and record from ensembles of CA3 neurons. We used these approaches to show that targeted activation of CA3 neurons results in an increasing excitatory amplification seen only in CA3 cells when stimulating other CA3 cells, and not in CA1, perhaps reflecting the greater number of recurrent connections in CA3. To probe hippocampal spatial representations, we titrated input to the network by morphing VR environments during spatial navigation to assess the local CA3 as well as downstream CA1 responses. To this end, we found CA1 and CA3 neural population responses behave nonlinearly, consistent with attractor dynamics associated with the two stored representations. We interpret our findings as supporting classic theories of Hebbian learning and as the beginning of uncovering the relationship between hippocampal neural circuit activity and the computations implemented by their dynamics. Establishing this relationship is paramount to demystifying the neural underpinnings of cognition

On the role of the hippocampus in the acquisition, long-term retention and semanticisation of memory

Institute for Adaptive and Neural ComputationA consensus on how to characterise the anterograde and retrograde memory processes that are lost or spared after hippocampal damage has not been reached. In this thesis, I critically re-examine the empirical literature and the assumptions behind current theories. I formulate a coherent view of what makes a task hippocampally dependent at acquisition and how this relates to its long-term fate. Findings from a neural net simulation indicate the plausibility of my proposals. My proposals both extend and constrain current views on the role of the hippocampus in the rapid acquisition of information and in learning complex associations. In general, tasks are most likely to require the hippocampus for acquisition if they involve rapid, associative learning about unfamiliar, complex, low salience stimuli. However, none of these factors alone is sufficient to obligatorily implicate the hippocampus in acquisition. With the exception of associations with supra-modal information that are always dependent on the hippocampus, it is the combination of factors that is important. Detailed, complex information that is obligatorily hippocampally-dependent at acquisition remains so for its lifetime. However, all memories are semanticised as they age through the loss of detailed context-specific information and because generic cortically-represented information starts to dominate recall. Initially hippocampally dependent memories may appear to become independent of the hippocampus over time, but recall changes qualitatively. Multi-stage, lifelong post-acquisition memory processes produce semanticised re-representations of memories of differing specificity and complexity, that can serve different purposes. The model simulates hippocampal and cortical interactions in the acquisition and maintenance of episodic and semantic events, and behaves in accordance with my proposals. In particular, conceptualising episodic and semantic memory as representing points on a continuum of memory types appears viable. Support is also found for proposals on the relative importance of the hippocampus and cortex in the rapid acquisition of information and the acquisition of complex multi-model information; and the effect of existing knowledge on new learning. Furthermore, episodic and semantic events become differentially dependent on cortical and hippocampal components. Finally, as a memory ages, it is automatically semanticised and becomes cortically dependent

Artificial general intelligence: Proceedings of the Second Conference on Artificial General Intelligence, AGI 2009, Arlington, Virginia, USA, March 6-9, 2009

Artificial General Intelligence (AGI) research focuses on the original and ultimate goal of AI – to create broad human-like and transhuman intelligence, by exploring all available paths, including theoretical and experimental computer science, cognitive science, neuroscience, and innovative interdisciplinary methodologies. Due to the difficulty of this task, for the last few decades the majority of AI researchers have focused on what has been called narrow AI – the production of AI systems displaying intelligence regarding specific, highly constrained tasks. In recent years, however, more and more researchers have recognized the necessity – and feasibility – of returning to the original goals of the field. Increasingly, there is a call for a transition back to confronting the more difficult issues of human level intelligence and more broadly artificial general intelligence

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

De La Mettrie's Ghost

This book is about how we make choices. Drawing together evidence from 21st century chemistry to Victorian politics, enlightenment philosophy, Roman drama and beyond, it is a compelling hunt for the nature of free will

De La Mettrie's Ghost

This book is about how we make choices. Drawing together evidence from 21st century chemistry to Victorian politics, enlightenment philosophy, Roman drama and beyond, it is a compelling hunt for the nature of free will

Knowledge Modelling and Learning through Cognitive Networks

One of the most promising developments in modelling knowledge is cognitive network science, which aims to investigate cognitive phenomena driven by the networked, associative organization of knowledge. For example, investigating the structure of semantic memory via semantic networks has illuminated how memory recall patterns influence phenomena such as creativity, memory search, learning, and more generally, knowledge acquisition, exploration, and exploitation. In parallel, neural network models for artificial intelligence (AI) are also becoming more widespread as inferential models for understanding which features drive language-related phenomena such as meaning reconstruction, stance detection, and emotional profiling. Whereas cognitive networks map explicitly which entities engage in associative relationships, neural networks perform an implicit mapping of correlations in cognitive data as weights, obtained after training over labelled data and whose interpretation is not immediately evident to the experimenter. This book aims to bring together quantitative, innovative research that focuses on modelling knowledge through cognitive and neural networks to gain insight into mechanisms driving cognitive processes related to knowledge structuring, exploration, and learning. The book comprises a variety of publication types, including reviews and theoretical papers, empirical research, computational modelling, and big data analysis. All papers here share a commonality: they demonstrate how the application of network science and AI can extend and broaden cognitive science in ways that traditional approaches cannot

Mathematical foundations for a compositional account of the Bayesian brain

This dissertation reports some first steps towards a compositional account of active inference and the Bayesian brain. Specifically, we use the tools of contemporary applied category theory to supply functorial semantics for approximate inference. To do so, we define on the 'syntactic' side the new notion of Bayesian lens and show that Bayesian updating composes according to the compositional lens pattern. Using Bayesian lenses, and inspired by compositional game theory, we define fibrations of statistical games and classify various problems of statistical inference as corresponding sections: the chain rule of the relative entropy is formalized as a strict section, while maximum likelihood estimation and the free energy give lax sections. In the process, we introduce a new notion of 'copy-composition'. On the 'semantic' side, we present a new formalization of general open dynamical systems (particularly: deterministic, stochastic, and random; and discrete- and continuous-time) as certain coalgebras of polynomial functors, which we show collect into monoidal opindexed categories (or, alternatively, into algebras for multicategories of generalized polynomial functors). We use these opindexed categories to define monoidal bicategories of 'cilia': dynamical systems which control lenses, and which supply the target for our functorial semantics. Accordingly, we construct functors which explain the bidirectional compositional structure of predictive coding neural circuits under the free energy principle, thereby giving a formal mathematical underpinning to the bidirectionality observed in the cortex. Along the way, we explain how to compose rate-coded neural circuits using an algebra for a multicategory of linear circuit diagrams, showing subsequently that this is subsumed by lenses and polynomial functors. Because category theory is unfamiliar to many computational neuroscientists and cognitive scientists, we have made a particular effort to give clear, detailed, and approachable expositions of all the category-theoretic structures and results of which we make use. We hope that this dissertation will prove helpful in establishing a new "well-typed'' science of life and mind, and in facilitating interdisciplinary communication

Mathematical Foundations for a Compositional Account of the Bayesian Brain

This dissertation reports some first steps towards a compositional account of active inference and the Bayesian brain. Specifically, we use the tools of contemporary applied category theory to supply functorial semantics for approximate inference. To do so, we define on the `syntactic' side the new notion of Bayesian lens and show that Bayesian updating composes according to the compositional lens pattern. Using Bayesian lenses, and inspired by compositional game theory, we define fibrations of statistical games and classify various problems of statistical inference as corresponding sections: the chain rule of the relative entropy is formalized as a strict section, while maximum likelihood estimation and the free energy give lax sections. In the process, we introduce a new notion of `copy-composition'. On the `semantic' side, we present a new formalization of general open dynamical systems (particularly: deterministic, stochastic, and random; and discrete- and continuous-time) as certain coalgebras of polynomial functors, which we show collect into monoidal opindexed categories (or, alternatively, into algebras for multicategories of generalized polynomial functors). We use these opindexed categories to define monoidal bicategories of cilia: dynamical systems which control lenses, and which supply the target for our functorial semantics. Accordingly, we construct functors which explain the bidirectional compositional structure of predictive coding neural circuits under the free energy principle, thereby giving a formal mathematical underpinning to the bidirectionality observed in the cortex. Along the way, we explain how to compose rate-coded neural circuits using an algebra for a multicategory of linear circuit diagrams, showing subsequently that this is subsumed by lenses and polynomial functors.Comment: DPhil thesis; as submitted. Main change from v1: improved treatment of statistical games. A number of errors also fixed, and some presentation improved. Comments most welcom

Serotonergic modulation of the ventral pallidum by 5HT1A, 5HT5A, 5HT7 AND 5HT2C receptors

Introduction: Serotonin's involvement in reward processing is controversial. The large number of serotonin receptor sub-types and their individual and unique contributions have been difficult to dissect out, yet understanding how specific serotonin receptor sub-types contribute to its effects on areas associated with reward processing is an essential step. Methods: The current study used multi-electrode arrays and acute slice preparations to examine the effects of serotonin on ventral pallidum (VP) neurons. Approach for statistical analysis: extracellular recordings were spike sorted using template matching and principal components analysis, Consecutive inter-spike intervals were then compared over periods of 1200 seconds for each treatment condition using a student’s t test. Results and conclusions: Our data suggests that excitatory responses to serotonin application are pre-synaptic in origin as blocking synaptic transmission with low-calcium aCSF abolished these responses. Our data also suggests that 5HT1a, 5HT5a and 5HT7 receptors contribute to this effect, potentially forming an oligomeric complex, as 5HT1a antagonists completely abolished excitatory responses to serotonin application, while 5HT5a and 5HT7 only reduced the magnitude of excitatory responses to serotonin. 5HT2c receptors were the only serotonin receptor sub-type tested that elicited inhibitory responses to serotonin application in the VP. These findings, combined with our previous data outlining the mechanisms underpinning dopamine's effects in the VP, provide key information, which will allow future research to fully examine the interplay between serotonin and dopamine in the VP. Investigation of dopamine and serotonins interaction may provide vital insights into our understanding of the VP's involvement in reward processing. It may also contribute to our understanding of how drugs of abuse, such as cocaine, may hijack these mechanisms in the VP resulting in sensitization to drugs of abuse