Immune and metabolic regulation of sensorimotor physiology and repair

The cellular phase of Alzheimer’s Disease and the path towards therapies

Multisensory perception in the metaverse

Genetic Analysis of Alzheimer's disease from mechanism to therapies (with some analogies to other diseases)

Neural architectures: what are they good for anyway?

The brain has a highly complex structure in terms of cell types and wiring between different regions. What is it for, if anything? I'll start this talk by asking what might an answer to this question even look like given that we can't run an alternative universe where our brains are structured differently. (Preview: we can do this with models!) I'll then talk about some of our work in two areas: (1) does the modular structure of the brain contribute to specialisation of function? (2) how do different cell types and architectures contribute to multimodal sensory processing?

TBD

“Open Raman Microscopy (ORM): A modular Raman spectroscopy setup with an open-source controller”

Raman spectroscopy is a powerful technique for identifying chemical species by probing their vibrational energy levels, offering exceptional specificity with a relatively simple setup involving a laser source, spectrometer, and microscope/probe. However, the high cost of Raman systems lacking modularity often limits exploratory research hindering broader adoption. To address the need for an affordable, modular microscopy platform for multimodal imaging, we present a customizable confocal Raman spectroscopy setup alongside an open-source acquisition software, ORM (Open Raman Microscopy) Controller, developed in Python. This solution bridges the gap between expensive commercial systems and complex, custom-built setups used by specialist research groups. In this presentation, we will cover the components of the setup, the design rationale, assembly methods, limitations, and its modular potential for expanding functionality. Additionally, we will demonstrate ORM’s capabilities for instrument control, 2D and 3D Raman mapping, region-of-interest selection, and its adaptability to various instrument configurations. We will conclude by showcasing practical applications of this setup across different research fields.

How do we sleep?

There is no consensus on if sleep is for the brain, body or both. But the difference in how we feel following disrupted sleep or having a good night of continuous sleep is striking. Understanding how and why we sleep will likely give insights into many aspects of health. In this talk I will outline our recent work on how the prefrontal cortex can signal to the hypothalamus to regulate sleep preparatory behaviours and sleep itself, and how other brain regions, including the ventral tegmental area, respond to psychosocial stress to induce beneficial sleep. I will also outline our work on examining the function of the glymphatic system, and whether clearance of molecules from the brain is enhanced during sleep or wakefulness.

Use case determines the validity of neural systems comparisons

Deep learning provides new data-driven tools to relate neural activity to perception and cognition, aiding scientists in developing theories of neural computation that increasingly resemble biological systems both at the level of behavior and of neural activity. But what in a deep neural network should correspond to what in a biological system? This question is addressed implicitly in the use of comparison measures that relate specific neural or behavioral dimensions via a particular functional form. However, distinct comparison methodologies can give conflicting results in recovering even a known ground-truth model in an idealized setting, leaving open the question of what to conclude from the outcome of a systems comparison using any given methodology. Here, we develop a framework to make explicit and quantitative the effect of both hypothesis-driven aspects—such as details of the architecture of a deep neural network—as well as methodological choices in a systems comparison setting. We demonstrate via the learning dynamics of deep neural networks that, while the role of the comparison methodology is often de-emphasized relative to hypothesis-driven aspects, this choice can impact and even invert the conclusions to be drawn from a comparison between neural systems. We provide evidence that the right way to adjudicate a comparison depends on the use case—the scientific hypothesis under investigation—which could range from identifying single-neuron or circuit-level correspondences to capturing generalizability to new stimulus properties

Maturation and plasticity of cortical interneurons

Neurogenic versus Oligodendrogenic progenitors in the postnatal brain. Different adaptations, different porperties

Foundation models in ophthalmology

Abstract to follow.

Bernstein Student Workshop Series

The Bernstein Student Workshop Series is an initiative of the student members of the Bernstein Network. It provides a unique opportunity to enhance the technical exchange on a peer-to-peer basis. The series is motivated by the idea of bridging the gap between theoretical and experimental neuroscience by bringing together methodological expertise in the network. Unlike conventional workshops, a talented junior scientist will first give a tutorial about a specific theoretical or experimental technique, and then give a talk about their own research to demonstrate how the technique helps to address neuroscience questions. The workshop series is designed to cover a wide range of theoretical and experimental techniques and to elucidate how different techniques can be applied to answer different types of neuroscience questions. Combining the technical tutorial and the research talk, the workshop series aims to promote knowledge sharing in the community and enhance in-depth discussions among students from diverse backgrounds.

Restoring function in advanced disease with photoreceptor cell replacement therapy

Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease

Beyond Volition

Voluntary actions are actions that agents choose to make. Volition is the set of cognitive processes that implement such choice and initiation. These processes are often held essential to modern societies, because they form the cognitive underpinning for concepts of individual autonomy and individual responsibility. Nevertheless, psychology and neuroscience have struggled to define volition, and have also struggled to study it scientifically. Laboratory experiments on volition, such as those of Libet, have been criticised, often rather naively, as focussing exclusively on meaningless actions, and ignoring the factors that make voluntary action important in the wider world. In this talk, I will first review these criticisms, and then look at extending scientific approaches to volition in three directions that may enrich scientific understanding of volition. First, volition becomes particularly important when the range of possible actions is large and unconstrained - yet most experimental paradigms involve minimal response spaces. We have developed a novel paradigm for eliciting de novo actions through verbal fluency, and used this to estimate the elusive conscious experience of generativity. Second, volition can be viewed as a mechanism for flexibility, by promoting adaptation of behavioural biases. This view departs from the tradition of defining volition by contrasting internally-generated actions with externally-triggered actions, and instead links volition to model-based reinforcement learning. By using the context of competitive games to re-operationalise the classic Libet experiment, we identified a form of adaptive autonomy that allows agents to reduce biases in their action choices. Interestingly, this mechanism seems not to require explicit understanding and strategic use of action selection rules, in contrast to classical ideas about the relation between volition and conscious, rational thought. Third, I will consider volition teleologically, as a mechanism for achieving counterfactual goals through complex problem-solving. This perspective gives a key role in mediating between understanding and planning on the one hand, and instrumental action on the other hand. Taken together, these three cognitive phenomena of generativity, flexibility, and teleology may partly explain why volition is such an important cognitive function for organisation of human behaviour and human flourishing. I will end by discussing how this enriched view of volition can relate to individual autonomy and responsibility.

Hallucinating mice, dopamine and immunity; towards mechanistic treatment targets for psychosis

Hallucinations are a core symptom of psychotic disorders and have traditionally been difficult to study biologically. We developed a new behavioral computational approach to measure hallucinations-like perception in humans and mice alike. Using targeted neural circuit manipulations, we identified a causal role for striatal dopamine in mediating hallucination-like perception. Building on this, we currently investigate the neural and immunological upstream regulators of these dopaminergic circuits with the goal to identify new biological treatment targets for psychosis

Off the rails - how pathological patterns of whole brain activity emerge in epileptic seizures

In most brains across the animal kingdom, brain dynamics can enter pathological states that are recognisable as epileptic seizures. Yet usually, brain operate within certain constraints given through neuronal function and synaptic coupling, that will prevent epileptic seizure dynamics from emerging. In this talk, I will bring together different approaches to identifying how networks in the broadest sense shape brain dynamics. Using illustrative examples from intracranial EEG recordings, disorders characterised by molecular disruption of a single neurotransmitter receptor type, to single-cell recordings of whole-brain activity in the larval zebrafish, I will address three key questions - (1) how does the regionally specific composition of synaptic receptors shape ongoing physiological brain activity; (2) how can disruption of this regionally specific balance result in abnormal brain dynamics; and (3) which cellular patterns underly the transition into an epileptic seizure.

Cortical seizure mechanisms: insights from calcium, glutamate and GABA imaging

Focal neocortical epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood, but is likely to relate to the intermittent collapse of feed-forward GABAergic inhibition. Inhibition could fail through multiple mechanisms, including (i) an attenuation or even reversal of the driving force for chloride in postsynaptic neurons because of intense activation of GABAA receptors, (ii) an elevation of potassium secondary to chloride influx leading to depolarization of neurons, or (iii) insufficient GABA release from interneurons. I shall describe the results of experiments using fluorescence imaging of calcium, glutamate or GABA in awake rodent models of neocortical epileptiform activity. Interictal spikes were accompanied by brief glutamate transients which were maximal at the initiation site and rapidly propagatedcentrifugally. GABA transients lasted longer than glutamate transients and were maximal ~1.5 mm from the focus. Prior to seizure initiation GABA transients were attenuated, whilst glutamate transients increased, consistent with a progressive failure of local inhibitory restraint. As seizures increased in frequency, there was a gradual increase in the spatial extent of spike-associated glutamate transients associated with interictal spikes. Neurotransmitter imaging thus reveals a progressive collapse of an annulus of feed-forward GABA release, allowing runaway recruitment of excitatory neurons as a fundamental mechanism underlying the escape of seizures from local inhibitory restraint.

Affective Intelligence in Digital Psychiatry: Would Wundt Woo?

Experimental Neuroscience Bootcamp

This course provides a fundamental foundation in the modern techniques of experimental neuroscience. It introduces the essentials of sensors, motor control, microcontrollers, programming, data analysis, and machine learning by guiding students through the “hands on” construction of an increasingly capable robot. In parallel, related concepts in neuroscience are introduced as nature’s solution to the challenges students encounter while designing and building their own intelligent system.

Representations of people in the brain

Faces and voices convey much of the non-verbal information that we use when communicating with other people. We look at faces and listen to voices to recognize others, understand how they are feeling, and decide how to act. Recent research in my lab aims to investigate whether there are similar coding mechanisms to represent faces and voices, and whether there are brain regions that integrate information across the visual and auditory modalities. In the first part of my talk, I will focus on an fMRI study in which we found that a region of the posterior STS exhibits modality-general representations of familiar people that can be similarly driven by someone’s face and their voice (Tsantani et al. 2019). In the second part of the talk, I will describe our recent attempts to shed light on the type of information that is represented in different face-responsive brain regions (Tsantani et al., 2021).

How People Form Beliefs

In this talk I will present our recent behavioural and neuroscience research on how the brain motivates itself to form particular beliefs and why it does so. I will propose that the utility of a belief is derived from the potential outcomes associated with holding it. Outcomes can be internal (e.g., positive/negative feelings) or external (e.g., material gain/loss), and only some are dependent on belief accuracy. We show that belief change occurs when the potential outcomes of holding it alters, for example when moving from a safe environment to a threatening environment. Our findings yield predictions about how belief formation alters as a function of mental health. We test these predictions using a linguistic analysis of participants’ web searches ‘in the wild’ to quantify the affective properties of information they consume and relate those to reported psychiatric symptoms. Finally, I will present a study in which we used our framework to alter the incentive structure of social media platforms to reduce the spread of misinformation and improve belief accuracy.

Chandelier cells shine a light on the emergence of GABAergic circuits in the cortex

GABAergic interneurons are chiefly responsible for controlling the activity of local circuits in the cortex. Chandelier cells (ChCs) are a type of GABAergic interneuron that control the output of hundreds of neighbouring pyramidal cells through axo-axonic synapses which target the axon initial segment (AIS). Despite their importance in modulating circuit activity, our knowledge of the development and function of axo-axonic synapses remains elusive. We have investigated the emergence and plasticity of axo-axonic synapses in layer 2/3 of the somatosensory cortex (S1) and found that ChCs follow what appear to be homeostatic rules when forming synapses with pyramidal neurons. We are currently implementing in vivo techniques to image the process of axo-axonic synapse formation during development and uncover the dynamics of synaptogenesis and pruning at the AIS. In addition, we are using an all-optical approach to both activate and measure the activity of chandelier cells and their postsynaptic partners in the primary visual cortex (V1) and somatosensory cortex (S1) in mice, also during development. We aim to provide a structural and functional description of the emergence and plasticity of a GABAergic synapse type in the cortex.

Theories of consciousness: beyond the first/higher-order distinction

Theories of consciousness are commonly grouped into "first-order" and "higher-order" families. As conventional wisdom has it, many more animals are likely to be conscious if a first-order theory is correct. But two recent developments have put pressure on the first/higher-order distinction. One is the argument (from Shea and Frith) that an effective global workspace mechanism must involve a form of metacognition. The second is Lau's "perceptual reality monitoring" (PRM) theory, a member of the "higher-order" family in which conscious sensory content is not re-represented, only tagged with a temporal index and marked as reliable. I argue that the first/higher-order distinction has become so blurred that it is no longer particularly useful. Moreover, the conventional wisdom about animals should not be trusted. It could be, for example, that the distribution of PRM in the animal kingdom is wider than the distribution of global broadcasting.

Spontaneous Emergence of Computation in Network Cascades

Neuronal network computation and computation by avalanche supporting networks are of interest to the fields of physics, computer science (computation theory as well as statistical or machine learning) and neuroscience. Here we show that computation of complex Boolean functions arises spontaneously in threshold networks as a function of connectivity and antagonism (inhibition), computed by logic automata (motifs) in the form of computational cascades. We explain the emergent inverse relationship between the computational complexity of the motifs and their rank-ordering by function probabilities due to motifs, and its relationship to symmetry in function space. We also show that the optimal fraction of inhibition observed here supports results in computational neuroscience, relating to optimal information processing.

Sharing data from your in vivo studies

The Problem of Testimony

The talk will detail work drawing on behavioural results, formal analysis, and computational modelling with agent-based simulations to unpack the scale of the challenge humans face when trying to work out and factor in the reliability of their sources. In particular, it is shown how and why this task admits of no easy solution in the context of wider communication networks, and how this will affect the accuracy of our beliefs. The implications of this for the shift in the size and topology of our communication networks through the uncontrolled rise of social media are discussed.

Untitled Seminar

How evidence synthesis can boost in vivo credibility

As part of the BNA's ongoing Credibility in Neuroscience work, this series of three short webinars will provide neuroscience researchers working in an in vivo setting with tips on how to improve the credibility of their work. Each webinar will be hosted by Emily Sena, member of the BNA's Credibility Advisory Board, with the opportunity for questions.

Activity-dependent Gene Therapy for Epilepsy

Modeling Visual Attention in Neuroscience, Psychology, and Machine Learning

Diversification of cortical inhibitory circuits & Molecular programs orchestrating the wiring of inhibitory circuitries

GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in some of these connectivity motifs might be liked to disease.   Our web pages for reference: https://devneuro.org.uk/marinlab/ & https://devneuro.org.uk/rico/default

The vestibular system: a multimodal sense

The vestibular system plays an essential role in everyday life, contributing to a surprising range of functions from reflexes to the highest levels of perception and consciousness. Three orthogonal semicircular canals detect rotational movements of the head and the otolith organs sense translational acceleration, including the gravitational vertical. But, how vestibular signals are encoded by the human brain? We have recently combined innovative methods for eliciting virtual rotation and translation sensations with fMRI to identify brain areas representing vestibular signals. We have identified a bilateral inferior parietal, ventral premotor/anterior insula and prefrontal network and confirmed that these areas reliably possess information about the rotation and translation. We have also investigated how vestibular signals are integrated with other sensory cues to generate our perception of the external environment.

NMC4 Short Talk: Transient neuronal suppression for exploitation of new sensory evidence

Decision-making in noisy environments with constant sensory evidence involves integrating sequentially-sampled evidence, a strategy formalized by diffusion models which is supported by decades behavioral and neural findings. By contrast, it is unknown whether this strategy is also used during decision-making when the underlying sensory evidence is expected to change. Here, we trained monkeys to identify the dominant color of a dynamically refreshed checkerboard pattern that doesn't become informative until after a variable delay. Animals' behavioral responses were briefly suppressed after an abrupt change in evidence, and many neurons in the frontal eye field displayed a corresponding dip in activity at this time, similar to the dip frequently observed after stimulus onset. Generalized drift-diffusion models revealed that behavior and neural activity were consistent with a brief suppression of motor output without a change in evidence accumulation itself, in contrast to the popular belief that evidence accumulation is paused or reset. These results suggest that a brief interruption in motor preparation is an important strategy for dealing with changing evidence during perceptual decision making.

NMC4 Keynote: Formation and update of sensory priors in working memory and perceptual decision making tasks

The world around us is complex, but at the same time full of meaningful regularities. We can detect, learn and exploit these regularities automatically in an unsupervised manner i.e. without any direct instruction or explicit reward. For example, we effortlessly estimate the average tallness of people in a room, or the boundaries between words in a language. These regularities and prior knowledge, once learned, can affect the way we acquire and interpret new information to build and update our internal model of the world for future decision-making processes. Despite the ubiquity of passively learning from the structured information in the environment, the mechanisms that support learning from real-world experience are largely unknown. By combing sophisticated cognitive tasks in human and rats, neuronal measurements and perturbations in rat and network modelling, we aim to build a multi-level description of how sensory history is utilised in inferring regularities in temporally extended tasks. In this talk, I will specifically focus on a comparative rat and human model, in combination with neural network models to study how past sensory experiences are utilized to impact working memory and decision making behaviours.

How does seeing help listening? Audiovisual integration in Auditory Cortex

Multisensory responses are ubiquitous in so-called unisensory cortex. However, despite their prevalence, we have very little understanding of what – if anything - they contribute to perception. In this talk I will focus on audio-visual integration in auditory cortex. Anatomical tracing studies highlight visual cortex as one source of visual input to auditory cortex. Using cortical cooling we test the hypothesis that these inputs support audiovisual integration in ferret auditory cortex. Behavioural studies in humans support the idea that visual stimuli can help listeners to parse an auditory scene. This effect is paralleled in single units in auditory cortex, where responses to a sound mixture can be determined by the timing of a visual stimulus such that sounds that are temporally coherent with a visual stimulus are preferentially represented. Our recent data therefore support the idea that one role for the early integration of auditory and visual signals in auditory cortex is to support auditory scene analysis, and that visual cortex plays a key role in this process.

NMC4 Short Talk: Directly interfacing brain and deep networks exposes non-hierarchical visual processing

A recent approach to understanding the mammalian visual system is to show correspondence between the sequential stages of processing in the ventral stream with layers in a deep convolutional neural network (DCNN), providing evidence that visual information is processed hierarchically, with successive stages containing ever higher-level information. However, correspondence is usually defined as shared variance between brain region and model layer. We propose that task-relevant variance is a stricter test: If a DCNN layer corresponds to a brain region, then substituting the model’s activity with brain activity should successfully drive the model’s object recognition decision. Using this approach on three datasets (human fMRI and macaque neuron firing rates) we found that in contrast to the hierarchical view, all ventral stream regions corresponded best to later model layers. That is, all regions contain high-level information about object category. We hypothesised that this is due to recurrent connections propagating high-level visual information from later regions back to early regions, in contrast to the exclusively feed-forward connectivity of DCNNs. Using task-relevant correspondence with a late DCNN layer akin to a tracer, we used Granger causal modelling to show late-DCNN correspondence in IT drives correspondence in V4. Our analysis suggests, effectively, that no ventral stream region can be appropriately characterised as ‘early’ beyond 70ms after stimulus presentation, challenging hierarchical models. More broadly, we ask what it means for a model component and brain region to correspond: beyond quantifying shared variance, we must consider the functional role in the computation. We also demonstrate that using a DCNN to decode high-level conceptual information from ventral stream produces a general mapping from brain to model activation space, which generalises to novel classes held-out from training data. This suggests future possibilities for brain-machine interface with high-level conceptual information, beyond current designs that interface with the sensorimotor periphery.

NMC4 Short Talk: Synchronization in the Connectome: Metastable oscillatory modes emerge from interactions in the brain spacetime network

The brain exhibits a rich repertoire of oscillatory patterns organized in space, time and frequency. However, despite ever more-detailed characterizations of spectrally-resolved network patterns, the principles governing oscillatory activity at the system-level remain unclear. Here, we propose that the transient emergence of spatially organized brain rhythms are signatures of weakly stable synchronization between subsets of brain areas, naturally occurring at reduced collective frequencies due to the presence of time delays. To test this mechanism, we build a reduced network model representing interactions between local neuronal populations (with damped oscillatory response at 40Hz) coupled in the human neuroanatomical network. Following theoretical predictions, weakly stable cluster synchronization drives a rich repertoire of short-lived (or metastable) oscillatory modes, whose frequency inversely depends on the number of units, the strength of coupling and the propagation times. Despite the significant degree of reduction, we find a range of model parameters where the frequencies of collective oscillations fall in the range of typical brain rhythms, leading to an optimal fit of the power spectra of magnetoencephalographic signals from 89 heathy individuals. These findings provide a mechanistic scenario for the spontaneous emergence of frequency-specific long-range phase-coupling observed in magneto- and electroencephalographic signals as signatures of resonant modes emerging in the space-time structure of the Connectome, reinforcing the importance of incorporating realistic time delays in network models of oscillatory brain activity.

Advancing Brain-Computer Interfaces by adopting a neural population approach

Brain-computer interfaces (BCIs) have afforded paralysed users “mental control” of computer cursors and robots, and even of electrical stimulators that reanimate their own limbs. Most existing BCIs map the activity of hundreds of motor cortical neurons recorded with implanted electrodes into control signals to drive these devices. Despite these impressive advances, the field is facing a number of challenges that need to be overcome in order for BCIs to become widely used during daily living. In this talk, I will focus on two such challenges: 1) having BCIs that allow performing a broad range of actions; and 2) having BCIs whose performance is robust over long time periods. I will present recent studies from our group in which we apply neuroscientific findings to address both issues. This research is based on an emerging view about how the brain works. Our proposal is that brain function is not based on the independent modulation of the activity of single neurons, but rather on specific population-wide activity patters —which mathematically define a “neural manifold”. I will provide evidence in favour of such a neural manifold view of brain function, and illustrate how advances in systems neuroscience may be critical for the clinical success of BCIs.

Spatial summation for motion detection

The wonders and complexities of brain microstructure: Enabling biomedical engineering studies combining imaging and models

Brain microstructure plays a key role in driving the transport of drug molecules directly administered to the brain tissue as in Convection-Enhanced Delivery procedures. This study reports the first systematic attempt to characterize the cytoarchitecture of commissural, long association and projection fiber, namely: the corpus callosum, the fornix and the corona radiata. Ovine samples from three different subjects have been imaged using scanning electron microscope combined with focused ion beam milling. Particular focus has been given to the axons. For each tract, a 3D reconstruction of relatively large volumes (including a significant number of axons) has been performed. Namely, outer axonal ellipticity, outer axonal cross-sectional area and its relative perimeter have been measured. This study [1] provides useful insight into the fibrous organization of the tissue that can be described as composite material presenting elliptical tortuous tubular fibers, leading to a workflow to enable accurate simulations of drug delivery which include well-resolved microstructural features.  As a demonstration of the use of these imaging and reconstruction techniques, our research analyses the hydraulic permeability of two white matter (WM) areas (corpus callosum and fornix) whose three-dimensional microstructure was reconstructed starting from the acquisition of the electron microscopy images. Considering that the white matter structure is mainly composed of elongated and parallel axons we computed the permeability along the parallel and perpendicular directions using computational fluid dynamics [2]. The results show a statistically significant difference between parallel and perpendicular permeability, with a ratio about 2 in both the white matter structures analysed, thus demonstrating their anisotropic behaviour. This is in line with the experimental results obtained using perfusion of brain matter [3]. Moreover, we find a significant difference between permeability in corpus callosum and fornix, which suggests that also the white matter heterogeneity should be considered when modelling drug transport in the brain. Our findings, that demonstrate and quantify the anisotropic and heterogeneous character of the white matter, represent a fundamental contribution not only for drug delivery modelling but also for shedding light on the interstitial transport mechanisms in the extracellular space. These and many other discoveries will be discussed during the talk." "1. https://www.researchsquare.com/article/rs-686577/v1, 2. https://www.pnas.org/content/118/36/e2105328118, 3. https://ieeexplore.ieee.org/abstract/document/9198110

Behavioural and neural basis of instinctive escape

Wiring & Rewiring: Experience-Dependent Circuit Development and Plasticity in Sensory Cortices

To build an appropriate representation of the sensory stimuli around the world, neural circuits are wired according to both intrinsic factors and external sensory stimuli. Moreover, the brain circuits have the capacity to rewire in response to altered environment, both during early development and throughout life. In this talk, I will give an overview about my past research in studying the dynamic processes underlying functional maturation and plasticity in rodent sensory cortices. I will also present data about the current and future research in my lab – that is, the synaptic and circuit mechanisms by which the mature brain circuits employ to regulate the balance between stability and plasticity. By applying chronic 2-photon calcium and close-loop visual exposure, we studied the circuit changes at single-neuron resolution to show that concurrent running with visual stimulus is required to drive neuroplasticity in the adult brain.

Dual lecture: Diversification of cortical inhibitory circuits & Molecular programs orchestrating the wiring of inhibitory circuitries

GABAergic interneurons play crucial roles in the regulation of neural activity in the cerebral cortex. In this Dual Lecture, Prof Oscar Marín and Prof Beatriz Rico will discuss several aspects of the formation of inhibitory circuits in the mammalian cerebral cortex. Prof. Marín will provide an overview of the mechanisms regulating the generation of the remarkable diversity of GABAergic interneurons and their ultimate numbers. Prof. Rico will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex, and how alterations in some of these connectivity motifs might be liked to disease.

Understanding the role of neural heterogeneity in learning

The brain has a hugely diverse and heterogeneous nature. The exact role of heterogeneity has been relatively little explored as most neural models tend to be largely homogeneous. We trained spiking neural networks with varying degrees of heterogeneity on complex real-world tasks and found that heterogeneity resulted in more stable and robust training and improved training performance, especially for tasks with a higher temporal structure. Moreover, the optimal distribution of parameters found by training was found to be similar to experimental observations. These findings suggest that heterogeneity is not simply a result of noisy biological processes, but it may play a crucial role for learning in complex, changing environments.

Improving Communication With the Brain Through Electrode Technologies

Over the past 30 years bionic devices such as cochlear implants and pacemakers, have used a small number of metal electrodes to restore function and monitor activity in patients following disease or injury of excitable tissues. Growing interest in neurotechnologies, facilitated by ventures such as BrainGate, Neuralink and the European Human Brain Project, has increased public awareness of electrotherapeutics and led to both new applications for bioelectronics and a growing demand for less invasive devices with improved performance. Coupled with the rapid miniaturisation of electronic chips, bionic devices are now being developed to diagnose and treat a wide variety of neural and muscular disorders. Of particular interest is the area of high resolution devices that require smaller, more densely packed electrodes. Due to poor integration and communication with body tissue, conventional metallic electrodes cannot meet these size and spatial requirements. We have developed a range of polymer based electronic materials including conductive hydrogels (CHs), conductive elastomers (CEs) and living electrodes (LEs). These technologies provide synergy between low impedance charge transfer, reduced stiffness and an ability to be provide a biologically active interface. A range of electrode approaches are presented spanning wearables, implantables and drug delivery devices. This talk outlines the materials development and characterisation of both in vitro properties and translational in vivo performance. The challenges for translation and commercial uptake of novel technologies will also be discussed.

The diachronic account of attentional selectivity

Many models of attention assume that attentional selection takes place at a specific moment in time which demarcates the critical transition from pre-attentive to attentive processing of sensory input. We argue that this intuitively appealing account is not only inaccurate, but has led to substantial conceptual confusion (to the point where some attention researchers offer to abandon the term ‘attention’ altogether). As an alternative, we offer a “diachronic” framework that describes attentional selectivity as a process that unfolds over time. Key to this view is the concept of attentional episodes, brief periods of intense attentional amplification of sensory representations that regulate access to working memory and response-related processes. We describe how attentional episodes are linked to earlier attentional mechanisms and to recurrent processing at the neural level. We present data showing that multiple sequential events can be involuntarily encoded in working memory when they appear during the same attentional episode, whether they are relevant or not. We also discuss the costs associated with processing multiple events within a single episode. Finally, we argue that breaking down the dichotomy between pre-attentive and attentive (as well as early vs. late selection) offers new solutions to old problems in attention research that have never been resolved. It can provide a unified and conceptually coherent account of the network of cognitive and neural processes that produce the goal-directed selectivity in perceptual processing that is commonly referred to as “attention”.

Feature selectivity can explain mismatch signals in mouse visual cortex

Sensory experience often depends on one’s own actions, including self-motion. Theories of predictive coding postulate that actions are regulated by calculating prediction error, which is the difference between sensory experience and expectation based on self-generated actions. Signals consistent with prediction error have been reported in mouse visual cortex (V1) when visual flow coupled to running was unexpectedly stopped. Here, we show such signals can be elicited by visual stimuli uncoupled to animal’s running. We recorded V1 neurons while presenting drifting gratings that unexpectedly stopped. We found strong responses to visual perturbations, which were enhanced during running. Perturbation responses were strongest in the preferred orientation of individual neurons and perturbation responsive neurons were more likely to prefer slow visual speeds. Our results indicate that prediction error signals can be explained by the convergence of known motor and sensory signals, providing a purely sensory and motor explanation for purported mismatch signals.

Measuring relevant features of the social and physical environment with imagery

The efficacy of images to create quantitative measures of urban perception has been explored in psychology, social science, urban planning and architecture over the last 50 years. The ability to scale these measurements has become possible only in the last decade, due to increased urban surveillance in the form of street view and satellite imagery, and the accessibility of such data. This talk will present a series of projects which make use of imagery and CNNs to predict, measure and interpret the social and physical environments of our cities.

Creating and controlling visual environments using BonVision

Real-time rendering of closed-loop visual environments is important for next-generation understanding of brain function and behaviour, but is often prohibitively difficult for non-experts to implement and is limited to few laboratories worldwide. We developed BonVision as an easy-to-use open-source software for the display of virtual or augmented reality, as well as standard visual stimuli. BonVision has been tested on humans and mice, and is capable of supporting new experimental designs in other animal models of vision. As the architecture is based on the open-source Bonsai graphical programming language, BonVision benefits from native integration with experimental hardware. BonVision therefore enables easy implementation of closed-loop experiments, including real-time interaction with deep neural networks, and communication with behavioural and physiological measurement and manipulation devices.