Seminar Archive
The popular Sussex Neuroscience Seminar Series has been running for over 10 years.
Speakers in 2024
- Dr Livia de Hoz, Charité (Berlin)
22 April 2024
When is noise salient? Subcortical coding of acoustic patterns
Relevant stimuli are embedded in a myriad of irrelevant ones coming from all directions and distances at any given point in time. Like in other sensory systems, structures along the auditory pathway use the immediate history of these stimuli to uncover patterns, deduce sources, identify relevant sounds and interpret the soundscape. Hypothesizing that the processing of background stimuli begins in subcortical structures, the lab focuses on the role of cortico-subcortical loops and uses behaviour, and large-scale electrophysiology to understand how this interpretation emerges. I will talk about recently obtained data on midbrain plasticity.
Dr Livia de Hoz studied Biology at the Complutense University in Madrid. She obtained a PhD at Edinburgh working on hippocampal memory with Richard Morris. Spending postdoctoral periods in Berlin, Jerusalem and Goettingen, she switched to working on auditory memory. She is now a group leader at the Berlin Neuroscience Research Center, at Charité university hospital.
- Dr Tessa Dekker, University College London (UCL)
15 April 2024
Neuroplasticity in visual development, deprivation, and sight-rescue
A robust learning system balances adaptability to new experiences with stability of key properties that would be costly to update. I will present work characterising neural stability and plasticity processes in typical visual development and in heritable eye diseases where the statistics of visual input are drastically altered. This work has important implications for emerging sight rescue gene therapies and how they impact on atypically developed systems, and I will present some recent studies investigating these implications in patients undergoing gene therapies.
I study how development of visual system contributes to adaptive perception and action, with a strong focus on neural mechanisms. My work involves: -behavioural psychophysics and eye-tracking to study developmental change - neuroimaging methods to understand the neural processes that support this change - fitting these data with formal models of neurocognitive processing to test quantitative hypotheses about underlying processes My previous work on normal visuomotor development has allowed me to perfect my methods and procedures for use with children aged 5-15 years. I am now adapting these methods for children with developmental disorders to study atypical development and plasticity at the brain level, and help develop new assessment and treatment evaluation methods.
- Professor Gerlai, University of Toronto
8 April 2024
Relational learning without the hippocampus: A fishy story?
Relational learning is a fundamentally important cognitive function. Without relational learning and memory, we would not be able to tie together loosely related memory pieces and form episodic memory, and would not be able to remember what happened to us throughout our life and who we are. Relational memory is subserved by the hippocampal formation and has been demonstrated in humans as well as various non-human mammalian species. Fish do not have a structure that would resemble the mammalian hippocampus. Does this mean fish cannot acquire relational memory? In this talk, I will explain why we should expect fish to be highly similar to humans (evolutionary conservation). I will also show evidence that a form of relational learning, spatial learning can be demonstrated in zebrafish. I will also discuss results of a psychopharmacology experiment in which a human NMDA-receptor antagonist (MK801) was tested for its ability to disrupt memory processes in zebrafish. I will conclude that the zebrafish is an excellent model organism with which one can study evolutionarily ancient, core mechanisms of memory, and that it may serve as an efficient tool for memory research.
Dr. Gerlai received his Ph.D. from the Hungarian Academy of Sciences with the highest distinction in 1987. He has held numerous academic positions in Europe and North America (Eötvös University of Budapest, Mount Sinai Hospital Research Institute of Toronto, Indiana University and Purdue University Indianapolis, University of Hawaii Honolulu). He also held leadership positions in the US biotechnology and biopharmaceutical research industry working as a Senior Research Scientist and Vice President (Genentech Inc. South San Francisco, Eli Lilly & Co. Indianapolis, Saegis Pharmaceuticals Half Moon Bay) before joining University of Toronto (Mississauga campus) in 2004, where he has been full professor at the Department of Psychology since 2008 and where he currently holds the John Carlin Roder Distinguished Professor in Behavioural Neuroscience position.
- Thomas Akam, Oxford University
18 March 2024
Efficient coding of a complex goal-directed behaviour in mouse medial-frontal cortex
Neuroscience has made substantial progress understanding the principles that determine how brains represent the external world, appealing to notions of efficiency – representations that reduce statistical redundancy in sensory input, and utility - representations that support useful computations. How brains represent the rich structure of our behaviours is less well understood, and it is unclear whether and how these principles may apply. I will present data which suggests that medial frontal cortex (mFC) contains an efficient code for the sequential structure of goal directed behaviours, which may support hierarchically organised action selection. We trained mice to navigate to visually cued goal locations in complex elevated mazes, and recorded neurons in medial frontal cortex using silicon probes. We observed two prominent patterns of activity: First, a population code for path-distance to goal in which different neurons fired at different distances, such that the population tiled the navigation trajectory. Second, location-direction tuning in which neurons fired when subjects traversed particular sections of the maze in a given direction. This often took the form of tuning to extended route segments, or motion towards bottle-neck locations, reminiscent of ‘options’ in hierarchical reinforcement learning (RL). The low-dimensional structure of this location-direction tuning across neurons spanned the same low-dimensional space as that of subject’s behavioural trajectories across trials - suggesting they may comprise an efficient code for behavioural trajectories. These perspectives are complementary, as work in machine learning suggests that sequence compression can discover useful options for hierarchical RL. We are currently working to understand how these representations may support route planning computations.
I am a behavioural neuroscientist interested in how brains generate flexible and adaptive behaviour. I originally trained in physics before joining the Wellcome Neuroscience PhD program at UCL, where I worked with Dimitri Kullman on how network oscillations can control communication in brain networks. I changed research direction for postdoc, and started working on how internal models of the world contribute to action selection. This took me first to Rui Costa’s lab at the Champalimaud Center Lisbon, and then to Oxford working with Mark Walton and Tim Behrens. I recently established my own lab at Oxford, where I study how brains build and use predictive models of the world to make good decisions in complex environments, using behaviour, brain recordings and manipulations in mice, combined with computational modelling.
- Juan Burrone, King's College London
11 March 2024
The emergence and plasticity of inhibitory synapses: from dendrites to the axon initial segment
An important question in neuroscience is to understand how excitatory and inhibitory neurons in the brain wire up during development. This highly dynamic period of brain development neatly encapsulates a key question in the field: how do circuits remain stable in the face of unrelenting change? Here, I will explore the rules behind the formation and plasticity of inhibitory synapses during the period of brain wiring. Specifically, I will focus on the inhibitory synapses formed onto two different subcellular compartments of pyramidal neurons: the dendritic tree and the axon initial segment. I will argue that although it is likely that rules vary across interneuron type depending on their subcellular target, they all serve to stabilise neuronal activity in the brain.
Juan Burrone is a Professor at the Centre for Developmental Neurobiology and the MRC Centre for Neurodevelopmental Disorders, at King’s College London, UK. He is also the Co-Lead for the Neurodevelopment theme at the Epilepsy Research Institute UK. He graduated from the University of Bristol (UK) in 1995 and obtained a PhD from Cambridge University in 2000, having worked under the supervision of Prof. Leon Lagnado at the MRC Laboratory of Molecular Biology (LMB). He then moved to the Molecular and Cellular Biology department at Harvard University, USA, to join Prof. Venkatesh Murthy’s lab as a postdoctoral fellow. In 2006 he joined King’s College London. His lab has contributed to our understanding of how connections between neurons form and mature in the brain, how neurons and circuits remain stable over time and how synapses convey information within circuits. Much of this work has focused on uncovering how information is converted from inputs to outputs and makes use of tools that probe neuronal function with good spatio-temporal precision. More recently, he has begun to implement these tools in the study of neuronal function in human neurons, particularly in the fields of epilepsy and neurodegeneration.
- M. Fernanda Ceriani, Fundación Instituto Leloir, Argentina
19 February 2024
Structural and functional consequences of circadian plasticity
Rhythmic rest-activity cycles are controlled by an endogenous clock. In Drosophila, this clock resides in about 150 neurons organized in clusters whose hierarchy changes in response to environmental conditions. The concerted activity of the circadian network is necessary for the adaptive responses to synchronizing stimuli. Clock neurons rely on neuropeptides (including members of the BMP retrograde pathway, Beckwith et al., 2013; Polcowñuk et al., 2021) and classical neurotransmitters (i.e., glycine, acetylcholine and glutamate, Frenkel et al., 2017, Guo et al., 2014) to coordinate their activity and give rise to a coherent output.
Additionally, our work revealed a novel mechanism relevant for the synchronization of the circadian network. The projections of an important class of clock neurons structurally remodel their axon terminals according to a circadian cycle (Fernández et al., 2008). We were able to show that such a phenomenon correlates with rhythmic changes in the number of synapses and hence the ability to synapse onto specific targets at given times across the day/night cycle (Gorostiza, Depetris-Chauvin et al., 2014); and it is not only limited to a specific group of circadian neurons (Duhart et al., 2020). We (and others) have examined some of the cellular mechanisms underlying this unusual form of plasticity, demonstrating that it relies on both activity dependent and independent mechanisms. Our current projects build on this body of work, which will be the focus of the seminar.M. Fernanda Ceriani holds a BSc (1990) and PhD (1996) in Biological Sciences from the School of Sciences, Universidad de Buenos Aires, Argentina. She did a postdoctoral fellowship supported by The Pew Charitable Trust in the laboratory of Steve A. Kay, at The Scripps Research Institute (La Jolla, CA) between 1997 and 2002. During this period she became interested in circadian biology and changed model system and field, embracing Drosophila neuroscience. At Scripps, she had a leading role in the characterization of core molecular mechanisms underlying the circadian clock. Since 2002, she holds a position at the National Council for Science and Technology (CONICET) and established her laboratory at the Fundación Instituto Leloir in Buenos Aires. Her research program focuses on the molecular and cellular basis of rhythmic behavior, with an interest on how this process is affected by aging. In particular, they investigate how central pacemaker neurons in the fly brain convey time of day information to the rest of the circadian network. From 2002-2007 she was appointed HHMI International Research Scholar. In 2011 she was awarded the Loreal/UNESCO ¨For Women in Science¨ Award (Argentine edition) for her work on the mechanisms underlying rhythmic behavior. In 2019 she was appointed to the Academia de Ciencias de America Latina (ACAL) and in 2021 became an EMBO-associate member. Over 20 MSc and PhD students obtained their degree under her direct supervision.
- Elisabetta Versace, Queen Mary University of London
12 February 2024
Foundations of cognition: from physics to minds
What aspects of the environment are reflected in the architecture of animal cognition? It’s easier to address this question by looking at animal species that soon after birth can move around autonomously and have an accurate perception of their world. These precocial animals, such as domestic chicks and tortoise hatchlings, provide a unique opportunity to investigate ideas that are present at the beginning of life and that do not depend on learning and experience but constitute the building blocks of mental life. I’ll discuss with you some of the traces of physics and the environment that support the presence of a colourful and dynamic slate in early minds.
Elisabetta Versace is a Royal Society Senior Research fellow and Senior lecturer at Queen Mary University of London, where she leads the Prepared minds lab, a research group that investigates how evolution has shaped animal minds and how minds support effective interactions with the environment. In the fields of animal cognition and evolution of behaviour, she focuses on predispositions, imprinting and sensitive periods, pattern learning, time processing, lateralisation and experimental evolution of behaviour
- Christelle Baunez, CNRS & Aix-Marseille Université
5 February 2024
How direct social presence modulates drug intake and role of the subthalamic nucleus in this effects
Drug consumption often occurs in a social context that has been studied by social sciences but relatively poorly by neuroscientists. Here we have investigated the influence of either the direct presence of a peer or playback of ultrasonic vocalizations of a peer during self-administration sessions of cocaine or alcohol in rats. We have further studied the influence of the familiarity with the peer (stranger vs familiar) on the consumption in these various conditions. We have found that the presence of a stranger rat or playback of positive USV emitted by a stranger are the best conditions to reduce cocaine consumption. This effect remains even after rats have gone through escalation of cocaine intake and was also found in a study assessing human consumption (Giorla et al 2022). In our rats studies, we have shown that this influence of the social context can be modulated by manipulations (lesions, deep brain stimulation at high frequency or optogenetic inhibition) of the subthalamic nucleus (STN). Taken together, our results suggest that manipulation of both the social context and the STN could be beneficial to treat addiction.
Dr. Christelle Baunez, is Directrice de Recherche at the CNRS, leader of the team ‘Basal Ganglia, Motivation and Reward’ (BAGAMORE) at the Institut de Neurosciences de la Timone (INT) in Marseille (France). During her PhD thesis in Marseille on behavioral studies of pharmacological interactions between glutamate and dopamine within the basal ganglia, she started to be interested in the subthalamic nucleus (STN) as a possible target for the treatment of Parkinson’s disease. During her post-doctoral internship at Cambridge University (UK) (supervised by Prof. T.W. Robbins), she focused on the involvement of the STN in non-motor functions. She revealed the involvement of STN in attention and control of inhibition. She got her permanent position at the CNRS in 1997 and pursued her research on the functions of the STN, developing deep brain stimulation in behaving rats. One of her major finding, published in Nature Neuroscience in 2005 and PNAS in 2010, was to show that STN lesion or DBS reduces motivation for cocaine, while increasing motivation for food, suggesting that STN DBS could be applied to treat addiction. The most recent findings confirm it on other criteria of addiction (publication in 2018 in Mol. Psych and PNAS in 2021). The research in her team extends to non-human primate and parkinsonian patients and is mainly focused on motivation.
- Juraj Koudelka, University of Edinburgh
29 January 2024
2-photon microscopy to investigate neuro-glial-vascular function in vivo in health and disease
Cerebrovascular dysfunction is a key early feature in the development of diseases such as vascular cognitive impairment (VCI) and Alzheimer’s disease (AD) that is proposed to precede and trigger downstream degenerative and cognitive changes. Dr. Juraj Koudelka, University of Edinburgh, will talk about his use of 2-photon in vivo imaging to investigate vascular dysfunction in disease models including alterations in the neuro-glial-vascular unit, which controls local cerebral blood flow. In particular, he will focus on two projects: firstly to investigate the spatio-temporal relationship between astrocytic calcium signalling and vascular haemodynamics in a mouse model of AD and secondly how microglia state might influence microglia-endothelial cell cross talk and white matter integrity in VCI.
Juraj Koudelka did his BSc in Neuroscience at the University of Edinburgh. His PhD was also at Edinburgh and was supervised by Liliana Minichiello. In his PhD he studied receptor docking sites in rodent gustatory development, finishing in 2013. After a short stint as a post-doc studying embryonic stem cells at the Scottish Centre for Regenerative Medicine he joined Karen Horsburgh's lab in 2014 at the now Centre for Discovery Brain Sciences. Since 2018 he has been both imaging lead in the Dementia Research Institute at Edinburgh and a post-doc for Karen Horsburgh. He leads the 2-P in vivo imaging facility and works with several groups to study various aspects of the neurvascular unit in the context of dementia.
- Alfredo Spagna, Columbia University, US
22 January 2024
The role of frontoparietal attentional networks in visual conscious perception and voluntary imagination
How do attentional networks influence conscious perception? I will present data from two studies: one featuring magnetoencephalographic recordings, and the other featuring intracerebral recordings assessing the effects of supra-threshold peripheral spatial cues on the conscious perception of near-threshold Gabors. Behavioral and neuroimaging results converge on the importance of lateralized front-parietal networks in shaping our visual conscious perceptions. I'll then discuss the relevance of our findings with respect to current theories of consciousness and conclude by relating them to a less-studied form of visual perception: visual mental imagery. I will briefly review the literature regarding human imagination, and then show recent neuroimaging evidence obtained using 3T and 7T fMRI, pointing at the role of the frontoparietal networks in supporting imagination. I will conclude by bridging between the fields of visual perception and visual imagination, pointing at the frontoparietal networks in these two processes.
Alfredo Spagna is a Faculty of the Psychology Department at Columbia University and Principal Investigator of The Living Lab. He is a Cognitive Neuroscientist by training, interested in learning how attention supports our daily functioning. He uses perception and imagination as two examples to study the benefits of correct allocation of attentional resources. After completing his Ph.D. in Cognitive Neuroscience at the Department of Psychology, Sapienza, University of Rome, he did his first post-doc under the supervision of Dr. Jin Fan, the creator of the Attentional Network Task, and then with Paolo Bartolomeo, world renowned expert in hemispatial neglect.
Speakers in 2023
- Dr Paul Anastasiades University of Bristol, UK
11 December 2023
Synaptic development of sensory and prefrontal circuit
During postnatal development, the brain undergoes a series of processes that bring about its mature architecture. These include neuronal migration, apoptosis, synapse formation and maturation. The timeline of cortical maturation is thought to be hierarchical, with primary sensory areas maturing earlier than higher-order areas, such as the prefrontal cortex (PFC). The cortex is a laminar structure with distinct synaptic inputs targeting specific layers. Within each cortical area there is also evidence for layer-specific development. For example, sensory critical periods in the mouse somatosensory barrel cortex (S1BF) follow an “outside-in” pattern, occurring first in thalamo-recipient layer (L)4 followed by superficial L2/3. The maturation of the PFC is thought to be delayed to that of S1BF. However, much less is known about the timeline of this maturation, particularly with respect to the development of synaptic connectivity within specific layers. Determining this may provide insight into when different inputs or cell types undergo synapse maturation. This project aims to determine similarities and differences in the synaptic maturation of a primary sensory barrel cortex (S1BF) and the PFC. To do so we have developed a pipeline for high-throughput synaptic puncta analysis using transgenic mice that express the synaptic protein PSD-95 tagged to GFP. We will compare the maturation of synapses between layers and regions to determine both common rules and region-specific differences of synapse development between cortical areas.
I did an undergraduate degree in Biochemistry followed by a Masters in Neuroscience. My PhD was with Prof Simon Butt at Imperial College London / Oxford (we moved the lab halfway-through). My PhD studies focused on the development of cortical circuits in the somatosensory cortex, with particularly focus on the role of Nkx2.1 positive GABAergic interneurons. Motivated by the role of the prefrontal cortex in neurodevelopmental disorders, I then moved to New York University to the lab of Prof Adam Carter to work on the organisation and modulation of key cell types and circuits in the PFC. My main focus was the organisation of higher-order cortico-thalamic circuits and the role of different types of GABAergic interneurons in these networks. I moved to University of Bristol in late 2019 and my lab now focuses on the development of PFC circuits in health and disease. We are particularly interested in the mechanisms of adolescence brain development.
- Prof James E. McCutcheon, UiT The Arctic University of Norway, Norway
7 December 2023
Exploring the neural and behavioural signatures of protein appetite
Acquiring the necessary balance of nutrients in one’s diet is a compelling problem faced by many animals including humans. For the macronutrient protein, this process is particularly pertinent as essential amino acids cannot be stored so must be constantly sourced through dietary choices. Thus, behavioural and physiological mechanisms likely exist to help compensate for any deficiency. Accordingly, we and others have shown that animals fed a low-protein diet develop a strong preference for protein over carbohydrate. This preference develops rapidly and is also associated with increased motivation for protein in an operant-responding paradigm. To explore the neural basis of this shift in behaviour we have been using a combination of calcium imaging, voltammetry, and activity-dependent “trapping” of neural populations in rodents. Using fibre photometry and voltammetry, we have shown that mesolimbic circuitry is modulated by the state of protein restriction with activity in ventral tegmental area and forebrain dopamine release elevated when animals are in need. In addition, with single cell multiphoton microscopy we have shown that an important projection to the VTA – GABAergic Vgat neurons in lateral hypothalamus – is similarly modulated by the state of protein restriction. Furthermore, we are using transgenic FosTRAP mice to identify how the state of protein restriction alters whole-brain patterns of neural activity evoked by consumption of protein and infusion of protein directly into the stomach.
Prof. James (Jamie) McCutcheon obtained his PhD at UCL (with Prof. SP Hunt) and conducted his post-doctoral research in the laboratories of Drs. Micky Marinelli (Rosalind Franklin University of Medicine & Science) and Mitch Roitman (University of Illinois at Chicago). Afterwards he became a PI and group leader at the Dept. of Neuroscience, Psychology & Behaviour, University of Leicester. Since 2019, he is a Professor in Biological Psychology at the Dept. of Psychology, UiT The Arctic University of Norway, Tromsø, Norway. His research focuses on the neurobiology of feeding and reward. In other words, how do we make choices about the foods we eat and how is our psychology affected by these choices. In particular, his group is interested in how the nutrient content of food (e.g. protein, salt, sugar etc.) is signalled to the brain and how this may change when we are in need of a certain nutrient. His lab studies these topics using a combination of in vivo neuroscience techniques including voltammetry, fibre photometry and electrophysiology.
- Prof Jianhua Cang, University of Virginia, US
5 December 2023
Mapping Visual Functions onto Molecular Cell Types in the Superior Colliculus
The superior colliculus (SC) is an evolutionarily conserved structure that receives direct retinal input in all vertebrates. It was the most sophisticated visual center until the neocortex evolved in mammals. Even in mice and tree shrews, mammalian species that are increasingly used in vision research, the vast majority of retinal ganglion cells project to the SC, making it a prominent visual structure in these animals. In this talk, I will review our recent functional studies of the mouse SC and describe our current efforts in linking visual response properties to genetically identified cell types.
- Prof James Kilner, University College London, UK
4 December 2023
Predictive coding and interoception
Interoception is the sensing and processing of signals that arise within our bodies. The most studied interoceptive signal is that from the heart. We know that the when the heart beats our ability to detect other sensory signals, touch, sight and hearing is reduced. However, why this occurs is not known. Recent theoretical accounts of interoception have focussed on the role of prediction in interoception, the predictive-coding models of interoception. However, there is little empirical data to support these accounts. In this talk I will propose that our awareness of our cardiac signals is not likely to be based on baroreceptor signals but rather on cardiac related signals that are present on all exteroceptive channels. I will suggest that to interpret cardiac related signals we require a fuller understanding of the links between heart rate and signals arising from the heart beating.
I have been working recently on research that includes interoception, neurophysiological human recordings and theoretical models of predictive coding that form the basis of the work I will present. I have worked in predictive coding for over 10 years. I published the first theoretical account of motor activity during action observation that proposed a predictive coding framework and I have published subsequently on the active inference theoretical framework and active inference models of motor control, action observation and the theoretical extension of these models to cover interoception through the lens of embodied cognition.
- Dr Irina Jarvers, University Regensburg, DE
27 November 2023
Risk Factors for the development of psychopathology in adolescence
- Robyn Grant, Manchester Metropolitan University, UK
20 November 2023
Mouse moustaches and walrus whiskers: why do mammals have whiskers?
Nearly all mammals have whiskers – sensory tactile hairs, also known as vibrissae. In fact, whiskers are only truly absent in a handful of species, including humans. However, much of what we know about whiskers comes from studying just a few species, such as laboratory rats and mice. In this presentation, I will present a snapshot of what we know about whiskers, drawing information from our comparative studies of whisker anatomy, development, evolution, and function. In particular, I will answer the following questions: how do whiskers work, develop, and evolve? And what are they for? I will also consider the applications of whisker research for mammalian behaviour, welfare, and conservation.
- Dr Philippa Johnson, Leiden University, NL
13 November 2023
A dynamic brain in a dynamic world
As we move through the world, it changes around us, and we change within it. In the first part of my talk, I will present work from my PhD, in which I investigated how we keep up with a changing world despite the delays intrinsic to transmission and processing of information in the brain. We used multivariate analysis of EEG data from humans to investigate the neural response to moving stimuli. We found that objects moving into a location on the screen were represented in that location much earlier than if they were flashed in the same location. This predictive encoding of position fully compensates the delays that accumulate during early stimulus processing. In the second part of my talk, I will present ongoing work from my postdoc, in which we are investigating how changes in internal brain state impact behaviour. Previous research has shown that mice show prolonged disengagement states when performing perceptual decision-making tasks, with attentional lapses clustered in time, rather than occurring independently. What neural and physiological processes trigger transitions into and out of disengagement states? Replicating previous results, we show that trials with slow response times are associated with larger and more variable baseline pupil, suggesting that high arousal is associated with disengaged behaviour. Next, we plan to use Hidden Markov models to identify engagement states based on response times. We expect that, prior to state switches, activity of arousal systems will cause increases in mean and variability of baseline pupil size. These findings will provide a starting point for exploring the cortical, subcortical and neuromodulatory processes preceding task (dis)engagement, with the ultimate aim of predicting behavioural state transitions before they happen. Overall, this research highlights the importance of considering temporal dynamics internal and external to the brain when seeking to understand behaviour.
I completed my PhD at the University of Melbourne, under the supervision of Hinze Hogendoorn and Stefan Bode, investigating how the brain compensates for neural delays during motion perception. Halfway through my PhD, I moved to the University of Amsterdam to visit Simon van Gaal’s research group, where I considered the implications of predictive representation on conscious perception. I am currently working as a postdoc with Anne Urai and Sander Nieuwenhuis at Leiden University, studying nonstationarity in decision-making behaviour.
- Dr Nadine Dijkstra, University College London, UK
30 October 2023
Constraints on distinguishing imagination from reality
Perceptual experience can be triggered by external signals coming from the outside world (perception) or by internal signals coming from memory (imagery). In the first part of this talk I will discuss to what extent imagery and perception rely on similar neural mechanisms. I will show that the same brain regions represent imagined and perceived stimuli in similar ways but that the way these representations come about is different. Next, I will discuss to what extent this overlap leads to confusion between imagination and reality and which cues the brain could use to keep the two apart. I will argue for the need for a perceptual reality monitoring system that evaluates different sources of information to determine whether sensory signals reflect imagination or reality.
Dr Nadine Dijkstra investigates computational and neural mechanisms of mental imagery. She obtained her PhD in Artificial Intelligence at the Donders Institute in Nijmegen in 2019 under supervision of Prof. Marcel van Gerven. After her PhD, she obtained two Postdoctoral Fellowships (Rubicon and Marie Curie) to investigate perceptual reality monitoring at the Wellcome Centre for Human Neuroimaging at University College London, where she is currently working as a Senior Research Fellow in collaboration with Prof. Stephen Fleming and Dr. Peter Kok.
- Prof James Hodge, Bristol University, UK
16 October 2023
Drosophila circadian rhythms and models of neurodegenerative disease
James' talk will cover his lab’s research interests starting with the evolution of the membrane clock (https://gtr.ukri.org/projects?ref=BB%2FW000865%2F1) and ending with his lab’s functional characterisation of novel genes associated with Alzheimer’s disease.
Prof James Hodge studied Biochemistry and Physiology at Sheffield University. He completed a PhD on Potassium Channels in Drosophila with Prof Cahir O’Kane in the Genetics Department at Cambridge. His postdoctoral work was at Brandeis University, Boston with Prof Leslie Griffith, studying the role of CASK and CaMKII autophosphorylation in synaptic function and behaviour. His lab at the School of Physiology, Pharmacology and Neuroscience at Bristol University studies how neural circuit activity underlies circadian rhythms, sleep and memory using Drosophila, molecular genetics, electrophysiology, optogenetics and computational neuroscience. He is interested in the fundamental biology of these behaviours and how they evolved. In parallel his research addresses how circadian rhythms, sleep and memory are affected by ageing, drugs and diseases including Alzheimer’s, Parkinson’s, Down’s, schizophrenia, neuropathies and epilepsy. He collaborates with clinicians and Industry to study these diseases and test novel drugs.
- Juan Alvaro Gallego, Imperial College London, UK
2 October 2023
Understanding adaptive motor control through neural manifolds
The analysis of neural population activity during behaviour consistently uncovers low-dimensional mathematical structures that capture a large fraction of neural variability. These structures or “neural manifolds” are defined by the dominant patterns of covariation across neurons. Recent studies focusing on neural manifolds and the activity within them –the “latent dynamics”– have shed light into questions about cognition, motor control, and learning that had long remained elusive. In this talk, I will discuss some of our work to understand the emergence of neural manifolds and their role in the generation of behaviour using a combination of recordings from several mammalian species and computational models. First, I will present a recent study showing that, even if the brain of each individual of a given species is unique, preserved features of circuit architecture lead to equally preserved latent dynamics when two animals are engaged in similar behaviour. Then, I will discuss our ongoing efforts to understand the properties of these preserved neural manifolds. I will show that neural manifolds across the motor system are intrinsically nonlinear, with these nonlinearities becoming more evident for specific brain regions and during more complex behaviours. Finally, I will highlight some of our research studying the role the latent dynamics in the generation of adaptive behaviour. I will present a study showing that the changes in latent dynamics during motor adaptation may arise from a feedback-driven process that emerges from a recurrently connected circuit minimising ongoing motor errors. Thus, the study of neural manifolds and their associated latent dynamics provides insights into how individual animals consistently and flexibly perform a variety of behaviours, and may enable comparative studies across groups of individuals from the same of even different species.
- Tony Azevedo, University of Washington, US
11 September 2023
Architecture of synaptic input to leg and wing motor neurons in Drosophila
Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles. Because individual muscles may be used in many different behaviors, MN activity must be flexibly coordinated by dedicated premotor circuitry, the organization of which remains largely unknown. Here, we use comprehensive reconstruction of neuron anatomy and synaptic connectivity from volumetric electron microscopy (i.e., connectomics) to analyze the wiring logic of motor circuits controlling the Drosophila leg and wing. We find that both leg and wing premotor networks are organized into modules that link MNs innervating muscles with related functions. However, the connectivity patterns within leg and wing motor modules are distinct. Leg premotor neurons exhibit proportional gradients of synaptic input onto MNs within each module, revealing a novel circuit basis for hierarchical MN recruitment. In comparison, wing premotor neurons lack proportional synaptic connectivity, which may allow muscles to be recruited in different combinations or with different relative timing. By comparing the architecture of distinct limb motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.
Bio
Anthony Azevedo, Ph.D., is a Research Scientist in the Tuthill Lab in the Department of Physiology and Biophysics, at the University of Washington in Seattle. The Tuthill Lab studies the neural mechanisms that support limbed, terrestrial locomotion in Drosophila. The lab takes advantage of the wide suite of Drosophila genetic tools, together with novel, comprehensive mapping of neural circuits and 3D markerless limb tracking, to record neural activity from genetically and anatomically identified neurons during behavior. Dr. Azevedo received his PhD in Physiology and Biophysics from UW in 2011, where he investigated the molecular mechanisms controlling rhodopsin activity, the light absorbing opsin in rod photoreceptors. In 2012, he joined the lab of Rachel Wilson in the Department of Neurobiology at Harvard Medical School, where he studied mechanosensory processing in the Drosophila brain. In 2016, he joined the nascent lab of his friend and colleague, John Tuthill, back at the University of Washington, to study sensorimotor neural circuits that govern locomotion.
- Hermina Nedelscu, Scripps Research, US
7 September 2023
Neuronal Ensembles Regulating Opioid-Motivated Approach and Avoidance Behavior
Opioid Use Disorder (OUD) is a chronic, relapsing brain disease characterized by compulsive drug seeking and use, engaging specific neurocircuits. One of the major projection systems implicated in regulating behavior motivated by drugs of abuse including opioids is the basolateral amygdala (BLA) pathway to nucleus accumbens (NAc). However, the BLAàNAc projection mediates not only approach behavior, as required for drug seeking, but also avoidance responses. This introduces the question as to the mechanisms by which a single excitatory projection system mediates diametrically opposite behaviors. Our preliminary data revealed that morphine (a rewarding opioid agonist) and naloxone (an aversive opioid antagonist) recruit two distinct groups of neurons – neuronal ensembles or engrams – within the same (BLA) brain area. Moreover, selective activation of morphine vs. naloxone reactive BLA axon terminals in the NAc induced opposing conditioned place preference (CPP) and aversion (CPA) respectively. While these preliminary data establish a role for two discrete drug-reactive NAc-projecting BLA ensembles, a mechanism by which a single excitatory pathway orchestrates the execution of diametrically opposite behaviors remains to be elucidated. To address this, we developed an opto-dialysis method in order to excite each BLAàNAc ensemble reactive to morphine or naloxone and subsequently collect neurotransmitter samples for analysis on the mass spectrometer. The effect of unilateral optogenetic stimulation of the morphine or naloxone terminals in the NAc on the extracellular levels of neurotransmitters differed among the morphine- vs. naloxone-reactive ensembles, suggesting unique neurotransmitter combinations are released to support the diametrically opposing behaviors.
Bio
I am a neuroscientist working at the intersection of molecular neuroanatomy and behavior. My research interest is concerned with how experiences are instantiated in the brain's neurocircuitry to support maladaptive behavior relevant to human psychopathology. The focus of my work is dedicated to understanding the neurobiological basis of substance use disorders including mechanisms that lead to the development of dependence, attachment and withdrawal states, craving, relapse, and cognitive impairment. As an undergraduate student, I studied Biological Sciences at the University of California, Irvine. Following a short period in Japan where I trained in molecular neurobiology with Dr. Yamamoto at the University of Osaka Medical School, I began my graduate training at New York University (NYU) as a master's student with Dr. Chiye Aoki focusing on fear learning relevant for anxiety disorders. My work at NYU had a profound influence in my developing an interest in experience-dependent neuroplasticity. For my doctoral work I was a Marie Curie and a Japan Society for the Promotion of Science (JSPS) Fellow under the mentorship of Drs. Arbuthnott and Aoki, where I focused on structural neuroplasticity of neuronal populations that support acquired experiences including skills acquired during development. Subsequently, I was awarded a post-doctoral JSPS Fellowship and was hosted by Dr. Sugihara at Tokyo Medical and Dental University to conduct brain-wide examinations of long-range axonal trajectories in their entirety, in order to access neural circuits in detail. In 2017, I transitioned back to California to pursue my research goal of bridging neural circuit plasticity and behavior at The Scripps Research Institute. Currently, I am a Staff Scientist in the Department of Neuroscience investigating activity-based interrogations of groups of neurons - neuronal ensembles and engram cells - within discrete circuits to link activation of neurocircuits by environmental cues with drug-seeking behavior. I have a K01 grant from NIDA to study the control of opioid-motivated approach and avoidance behavior by neuronal ensembles.
- Dr Yuki Todo, Kanazawa University, Japan
14 August 2023
Computational and Experimental Studies on Visual Systems
Abstract
The talk focuses on the intersection of computational methods and experimental investigations in understanding visual systems. The presentation delves into how we are using computational techniques to model and simulate various aspects of visual processing, such as visual perception, and motion detection. Additionally, the talk highlights the integration of computational models with experimental results to gain insights into the underlying mechanisms of vision in humans and other organisms. By combining theoretical approaches with experimental findings, we aim to deepen our understanding of visual systems and make new predictions that can be experimentally verified. These novel predictions can guide further experiments and contribute to our understanding of the visual system.
- Prof Geoff Goodhill, Washington University, US
7 August 2023
How fluid mechanics and energy expenditure constrain larval zebrafish behavior
Abstract
Animal behavior is strongly constrained by energy consumption. A natural manipulation which provides insight into this constraint is development, where an animal must adapt its movement to a changing energy landscape as its body grows. Unlike many other animals, for fish it is relatively easy to estimate the energy consumed by their movements via fluid mechanics. Here we simulated the fluid mechanics of > 100,000 experimentally-recorded movement bouts from larval zebrafish at 3 different ages and 2 different fluid conditions as they hunted paramecia. We find that these fish adapt to their changing relationship with the fluid environment as they grow by adjusting the frequency with which they select different types of movements, so that more expensive movements are chosen less often. This strategy was preserved when fish were raised in an unnaturally viscous environment. This work suggests a general principle by which animals could minimize energy consumption in the face of changing energy costs over development.
Short Bio
Prof Goodhill originally trained in Mathematics, Physics, Artificial Intelligence and Cognitive Science in the UK. After postdoctoral work at the Salk Institute he started his own lab in the Neuroscience Department at Georgetown University Medical School, where he was awarded tenure. In 2005 he moved to Australia to take up a joint appointment between the Queensland Brain Institute and School of Mathematics and Physics at the University of Queensland in Brisbane. In 2021 he returned to the US to the departments of Developmental Biology and Neuroscience at Washington University School of Medicine, where he directs the new Center for Theoretical and Computational Neuroscience. Prof Goodhill has been awarded over 30 grants to fund his research from the NIH, NSF, DoD, Simons Foundation, Human Frontiers Science Foundation, Whitaker Foundation, Australian Research Council, and Australian National Health and Medical Research Council. He has trained over 30 PhD students and postdocs, many of whom are now faculty members in universities worldwide. From 2005-2010 he was Editor-in-Chief of the journal Network: Computation in Neural Systems, and has also served on the Editorial Boards of several other journals. In 2006 he founded the Australian Workshop on Computational Neuroscience and in 2015 the Systems and Computational Neuroscience DownUnder (SCiNDU) conference, which have both run regularly since then. He has taught courses in Medical Neuroscience, Developmental Neuroscience, Mathematical Neuroscience, Systems Neuroscience, Numerical Methods, and Scientific Computing. Besides giving many radio interviews and public lectures about his work he has also written several articles for The Conversation and given a TEDx talk.
- Prof Thomas Euler Universitaet Tuebingen, DE
17 July 2023
Mouse vision: neither tiny primates nor furry fish
- Olena Riabinina Durham university, UK
10 July 2023
Olfaction in Anopheles gambiae mosquitoes
Abstract:
Malaria is a vector-borne disease that currently affects half of the world population and leads to >400,000 deaths/year. Larval and adult mosquitoes use olfaction to locate their human hosts and food sources, and to avoid harmful substances in their environment. Due to the lack of suitable research tools until very recently, little is known about how individual smell-detecting neurons of mosquitoes respond to odorants. In addition, most of the research focusses on adult females, leaving larvae and adult males almost entirely overlooked. In my talk I will discuss our recent progress in understanding how a simple olfactory system of mosquito larvae works.
Bio:
Lena received MRes in Applied Physics, followed by a PhD in Behavioural Neuroscience at Sussex University, supervised by Thomas Collett, Natalie Hempel de Ibarra and Andrew Philippides. After several postdocs in the UK and the US, most importantly the one at Chris Potter’s lab at the Johns Hopkins University, Lena received a Marie Curie fellowship, hosted at Richard Baines’ lab at Manchester University. Lena worked on ants, bumblebees, flies and mosquitoes, studying their visual navigation, mechanosensation and olfaction by employing a variety of research methods. At Durham University, the InsectNeuroLab led by Lena focusses on sensory neuroecology and genetics of bumblebees, mosquitoes and flies.
- Prof Hélèn Plun-Favreou University College London, UK
3 July 2023
Mitophagy: from genetics to biology, and back
Abstract:
Parkinson’s disease (PD) is a common incurable neurodegenerative disease. The identification of genetic variants via genome-wide association studies (GWAS) has considerably advanced our understanding of the PD genetic risk. Understanding the functional significance of the risk loci is now a critical step towards translating these genetic advances into an enhanced biological understanding of the disease. Previous functional analyses of PINK1 and PRKN, two genes associated with autosomal recessive PD, have highlighted the selective degradation of damaged mitochondria (mitophagy) as a key contributor to disease pathogenesis. We used a PINK1-dependent mitophagy screening assay to evaluate the functional significance of risk genes identified through GWAS. We identified two new regulators of PINK1-mitophagy, KAT8 and KANSL1, part of the histone acetylating non-specific lethal (NSL) complex. This complex localises to the nucleus, where it has a role in transcriptional activation. We further showed that genes encoding the NSL complex are highly correlated with and regulate genes associated with Parkinson’s disease. Overall, these findings reveal a potentially wider role for this protein complex in regulating genes and pathways implicated in PD.aining on a head-fixed tactile object localization task. Using information theoretical analysis, I will demonstrate that learning is supported by gradual changes at the individual neuron and population levels, and that these contribute differently to increase sensory and behavior-related information. This, in turn, has an effect in generating novel, task-specific information, necessary for behavioral improvement.
Bio:
After a PhD in France (Angers University) in signal transduction, Helene did her postdoctoral work with Professor Julian Downward at CRUK. The discoveries and work she did in this area led her towards neurodegeneration and she was successful in being appointed to an MRC Career Development Fellowship to work in the Department of Molecular Neuroscience at UCL Institute of Neurology. Since her arrival in 2007 Helene has carried out some significant work on the molecular pathways associated with mitophagy and other mitochondrial dysfunctions in neurodegenerative disorders. The approaches they have undertaken require live cell microscopy and complex molecular and cellular biology, and provide a more complete picture of the pathways that play a role in the pathogenesis of neurodegeneration.
- Dr Mariangela Panniello IIT Genoa, Italy"
26 June 2023
On the emergence of sensory and behavior-related information in primary cortex during learning
Abstract:
Over the course of sensory learning primary cortical areas carry not only sensory, but also behavior-related information. On an individual neuron level, a variety of learning-related changes have been observed, including response sharpening and changes in response magnitude. On the other hand, some studies report minimal changes in the response properties of individual neurons as learning progresses, and instead find alterations at the population level, for example in the relative spike-timing, or in population activity correlations. The field still lacks 1) a systematic description of how sensory and behavioral information emerge and integrate with one another during learning, and 2) a comprehensive picture of the relative contribution of individual cells versus neuronal populations in this process. During the talk, I will present our results obtained using longitudinal two-photon imaging to record the activity of excitatory neurons in layers 2 and 3 of the mouse barrel cortex before, during and after training on a head-fixed tactile object localization task. Using information theoretical analysis, I will demonstrate that learning is supported by gradual changes at the individual neuron and population levels, and that these contribute differently to increase sensory and behavior-related information. This, in turn, has an effect in generating novel, task-specific information, necessary for behavioral improvement.
Bio:
Mariangela received a MSc in Neurobiology from the University of Pisa. She then moved to the University of Oxford, where she obtained a PhD in Physiology under the supervision of Prof Andrew King and Dr Kerry Walker. There, she studied the spatial organization of auditory responses in the auditory cortex of rodents and ferrets using 2p imaging. She then worked as a postdoctoral researcher in the group led by Dr Michael Kohl, again at Oxford, where she started working on the somatosensory cortex. in 2020 she moved to The Italian Institute of Technology, in Genova, where she joined the group led by Tommaso Fellin, and one year later she received a Marie Curie Fellowship to carry out her research.
- Dr Anders Garm University of Copenhagen, UK
5 June 2023
Compound match filters and potential colour perception in the visual system of box jellyfish
Abstract:
In general there is a clear correlation between the complexity of the behavioural repertoire of an animal and the complexity of its nervous system. This is caused by more advanced behaviours demanding neural processing of large amounts of complex sensory input but often also by a requirement for more elaborate motor control. Still, animals with relatively simple body structure and nervous system sometimes display surprisingly complex behaviours. We have shown this to be true for box jellyfish - medusae of the cnidarian class Cubozoa. Box jellyfish have 24 eyes distributed on four sensory structures called rhopalia and eight of these eyes are image forming camera type eyes. Accordingly, they display a number of visually guided behaviours but the rhopalia, which also process the visual information, only possess 1000 neurons each. Our results have shown that an important part of the functionality are combinations of clever filters, compound matched filters, which ensures a minimal need for post-processing of the visual information. This includes the gaze control, visual field, low pass spatial filtering and temporal properties of the photoreceptors. Currently, we are examining how their several different opsins might add to the visual processing and this have led to surprising indications of colour vision.
- Dr Helen Barron University of Oxford, UK
22 May 2023
Binding memory for inference
- Dr Benedict Diederich Friedrich-Schiller-University, Jena, Germany
19 May 2023
UC2: A versatile and customizable low-cost 3D-printed open standard for microscopic imaging
- Prof Amy L Milton University of Cambridge, UK
15 May 2023
Reconsolidation-based approaches for the treatment of mental health disorders
Abstract:
Maladaptive emotional memories contribute to the persistence of numerous mental health disorders, including post-traumatic stress disorder (PTSD), drug addiction and obsessive-compulsive disorder (OCD). Targeting the reconsolidation of these maladaptive memories may provide avenues for new treatment development, though reconsolidation-based approaches also present challenges. This talk will consider some of the mechanisms by which pavlovian and instrumental memories become once again labile long after learning, and how this might influence the design of reconsolidation-based treatments for mental health disorders.
Bio:
Amy Milton is a University Professor in Behavioural Neuroscience in the Department of Psychology at the University of Cambridge, and Director of the Cambridge MiND (Memories in Neuropsychiatric Disorders) Lab. Her research focuses on the neurochemical and molecular mechanisms underlying memory reconsolidation, and their exploitation to develop new treatments for mental health disorders. She also has a strong interest in the development of translationally relevant models of mental health disorders, and facilitating dialogue between basic and clinical neuroscientists working in mental health. Amy's research, funded by the Medical Research Council, the Wellcome Trust and the Biotechnology and Biological Sciences Research Council, has applications to mental health disorders including drug addiction, post-traumatic stress disorder, and obsessive-compulsive disorder.
- Dr Varun Sreenivasan, King's College London, UK
10 May 2023
Excitation-Inhibition balance in the brain: Mechanisms, circuit function and disease
- Dr Michal Milczarek Cardiff University, UK
17 April 2023
The mammillary-thalamic-retrosplenial axis: from integration to consolidation
Abstract:
Current models of memory processing typically focus on the hippocampus. However, it is becoming evident that the acquisition, storage and retrieval of memories engages complex brain-wide networks. The circuit of Papez, or the extended memory system, processes multiple sensory modalities to aid spatial cognition, memory and emotion. One of its elements – the retrosplenial cortex – is uniquely positioned to integrate multiple information streams: it is strongly interconnected with the hippocampal formation, participates in the default mode network and belongs to a set of scene selective areas. Work in our group has shown retrosplenial contributions to the processing of visual stimuli, including visual cue-dependent navigation, acquisition and storage of long-term spatial memories and the concomitant microstructural plastic changes. We found the engagement of the retrosplenial cortex in long-term memory storage to be gradual and associated with the maturation of stable memory engrams. Moreover, we demonstrated the retrosplenial cortex to be vulnerable to chronic loss of its ascending inputs, including from the mammillary body-anterior thalamic pathway. Lesions of the mammillothalamic tract lead to diminished immediate-early gene staining and hypometabolism in the retrosplenial cortex and beyond as well as abnormal retrosplenial and hippocampal oscillatory activity patterns. In our most recent work, we show that temporary inactivation of the mammillary bodies specifically impairs the post-encoding stage of place memory formation while temporary inhibition of the retrosplenial cortex (or its inputs) recapitulates the effects of chronic lesions on spatial alternation tests.
- Prof Simon Luckman University of Manchester, UK
3 April 2023
Brainstem neurons: for better, for worse, in sickness and in health
Abstract:
We have shown previously the importance of parallel brainstem pathways in processing different modalities of anorectic signalling. For example, brainstem neurons containing prolactin-releasing peptide mediate normal gut-brain signalling of meal-related satiety. Other brainstem neurons, such as those that contain GLP-1 or the GDF15 receptor, GFRAL, do not respond to satiating signals but instead respond to stretch beyond normal stomach accommodation, as well as infectious and nausea-inducing agents. As many therapeutic drugs induce nausea and malaise, leading to problems with patient compliance, it is important to understand the underlying mechanisms which mediate these effects. In this presentation, I will outline our work which has characterised the neurons and brainstem pathways which mediate the aversive effects of common therapeutics, including current drugs used to treat metabolic diseases and cancer. In addition, I will describe a novel neuroendocrine pathway which abrogates the nausea produced by leading drugs prescribed to treat diabetes and obesity.
Bio:
Prof Luckman has over 35 years of experience using physiological models to investigate homeostatic brain mechanisms. His main interests are in neural integration with peripheral organs (and the environment), and how this affects appetite and body weight. He has published extensively on homeostatic regulation: current h index = 40, 78 peer-reviewed articles with an average citation of 61; including 11 papers with over 100 citations (source Scopus; includes recent publications in Cell Metabolism, Nature Communications, Current Biology, eLife and Molecular Metabolism). His group has used leading technologies to investigate brain pathways, including engineering his own conditional transgenic mice to allow the selective manipulation of identified neuronal populations (many of which he has shared with colleagues in the field). Since his own BBSRC-funded Advanced Post-doctoral Fellowship, he has supervised 19 research council/charity grants and 16 PhD studentships (including four Industrial Partnership Awards and five CASE PhDs). The focus of his academic work and teaching relates to brain regulation of energy homeostasis: an area of investigation which informs understanding of brain function, biological mechanisms maintaining health and novel therapeutic targets. His work involves fundamental bioscience to underpin other health research funders and industry. His first University post was part-funded by Astra Zeneca, and he went on to lead a Research Council and multi-Industry partner collaboration in Integrative Mammalian Biology. He continues as a long-term industrial collaborator with Eli Lilly and Novo Nordisk, providing evidence for novel drug programs (including on drugs currently undergoing Phase 2 and Phase 3 human trials).
- Dr Michel van den Oever Vrije Universiteit Amsterdam, Netherlands
27 March 2023
Progressive and experience-dependent adaptations in cortical engram cells
Abstract:
Accumulating evidence indicates that learned appetitive and aversive memories are encoded by sparsely distributed neurons that become highly activated during learning, so-called engram cells. My lab contributed to this by demonstrating that cortical engram cells are stable over time and thereby support memory persistence. However, little is known about experience-dependent differences in the organization of engram cell networks. Furthermore, the molecular and cellular mechanisms that underlie the stability of an engram cell population are poorly understood. In my presentation, I will show how differences in the intensity of an experience can influence the organization of an engram network, as well as engram cell-specific adapations that may support memory persistence.
Bio:
In 2008, I obtained a PhD in Neuroscience at the department of Molecular and Cellular Neurobiology, Vrije Universiteit Amsterdam. After a postdoctoral training at the lab of Dr. Sheena Josselyn at the Hospital for Sick Children in Toronto, Canada, I returned to Amsterdam, where I now head the Memory Circuits research team at the Center for Neurogenomics and Cognitive Research, VU Amsterdam. I participate in several research national and international consortia and received a VENI and VIDI grant from the talent program of the Netherlands Organization of Scientific Research (NWO). My research currently focuses on the spatial and temporal organization of persistent memories related to drugs of abuse and fearful experiences in the brain. Lab webpage here.
- Prof Hélèn Plun-Favreou University College London, UK
20 March 2023
Mitophagy: from genetics to biology, and back
Abstract:
Parkinson’s disease (PD) is a common incurable neurodegenerative disease. The identification of genetic variants via genome-wide association studies (GWAS) has considerably advanced our understanding of the PD genetic risk. Understanding the functional significance of the risk loci is now a critical step towards translating these genetic advances into an enhanced biological understanding of the disease. Previous functional analyses of PINK1 and PRKN, two genes associated with autosomal recessive PD, have highlighted the selective degradation of damaged mitochondria (mitophagy) as a key contributor to disease pathogenesis. We used a PINK1-dependent mitophagy screening assay to evaluate the functional significance of risk genes identified through GWAS. We identified two new regulators of PINK1-mitophagy, KAT8 and KANSL1, part of the histone acetylating non-specific lethal (NSL) complex. This complex localises to the nucleus, where it has a role in transcriptional activation. We further showed that genes encoding the NSL complex are highly correlated with and regulate genes associated with Parkinson’s disease. Overall, these findings reveal a potentially wider role for this protein complex in regulating genes and pathways implicated in PD.
Bio:
After a PhD in France (Angers University) in signal transduction, Helene did her postdoctoral work with Professor Julian Downward at CRUK. The discoveries and work she did in this area led her towards neurodegeneration and she was successful in being appointed to an MRC Career Development Fellowship to work in the Department of Molecular Neuroscience at UCL Institute of Neurology. Since her arrival in 2007 Helene has carried out some significant work on the molecular pathways associated with mitophagy and other mitochondrial dysfunctions in neurodegenerative disorders. The approaches they have undertaken require live cell microscopy and complex molecular and cellular biology, and provide a more complete picture of the pathways that play a role in the pathogenesis of neurodegeneration.
- Dr Rachel Parkinson University of Oxford, UK
13 March 2023
The taste of nectar: bee gustation and foraging preferences
Abstract:
Bees feed primarily on floral nectar and pollen. Nectar contains sugars, as well as various secondary compounds, including amino acids and plant metabolites. Pesticides also end up in nectar, posing a risk to pollinators. Relatively little is known about what bees can taste in nectar, and how they use this information to guide foraging decisions. We have found that bees possess a specialized mechanism for detecting sugars, involving three of the four gustatory receptor neurons contained within taste sensilla located on the mouthparts. This mechanism facilitates high-resolution detection of sugar compounds and may facilitate sugar discrimination. Despite their high affinity for sugars, bees display poor ability to discriminate potentially toxic compounds in nectar. I will explore mechanisms of bitter compound detection in bees and discuss how the presence of toxic nectar compounds affects foraging.
Bio:
Rachel is a neuroethologist and toxicologist, using behaviour and electrophysiology to study the effects of environmental change on insect brains and behaviour. She obtained her PhD in Biology from the University of Saskatchewan, Canada, where she investigated the effects of pesticides on visual motion detection in the locust. In 2019, Rachel held a Grass Fellowship in Neuroscience at the Marine Biological Laboratory (Woods Hole, USA), where she explored how pesticides affect visual responses of honeybees to optic flow. Her studies demonstrated that neonicotinoid pesticides impair visual motion detection in insects, leading to impaired collision avoidance and other visually-guided behaviours. Since 2020, Rachel has been at the University of Oxford with a Royal Society Newton International Fellowship studying taste in bees with Prof. Geraldine Wright. She has shown that bumblebees have a unique mechanism for detecting sugars that may facilitate sugar discrimination. Together with Prof. Wright, Rachel is working towards a broad understanding of how bees use taste to guide feeding and foraging, and how foraging is affected by the presence of agrochemicals.
- Dr Emma Cahill University of Bristol, UK
6 March 2023
Do you fear what I fear?: Individual differences in memory for threat detection in rats
Abstract:
In this talk, I will discuss the promises and pitfalls of the study of emotionally-driven behaviour using rodent models. When we attempt to study mechanisms underlying emotions such as fear or anxiety, we come up against some limitations of trying to model all these aspects in rodents. Nonetheless, psychological theories of memory and emotions, like fear, have provided a useful framework to refine the tasks and measures that we use. With these theories in mind, we will look at how threat detection by animals can be acquired by direct or vicarious experience or exist as ‘innate’ responses. We can model how a rodent learns about threats using pavlovian associative conditioning tasks, where the rodent learns that a specific stimulus was predictive of an aversive event. The imminence of a threat is assessed by either the threat cue physical proximity as close/distant, or by a psychological prediction of its likelihood as a recognisable predictable/unpredictable event. I will present some of our recent work on how the understanding of the cellular mechanisms of aversive learning can be leveraged to weaken persistent and overactive fear responses with the view to developing pharmacological or behavioural interventions for psychiatric disorders linked with fear and anxiety.
Bio:
Emma Cahill took her BA in Natural Sciences specialising in Neuroscience at Trinity College Dublin, where she contributed to projects on exercise-induced enhanced of recognition memory in the laboratory of Dr Áine Kelly. Emma then moved to France for her Masters in the team of Prof Serge Laroche at Orsay, where she studied learning deficits in a mouse model of Coffin-Lowry Syndrome. For her PhD, she focused on more cellular and molecular mechanisms underlying reinforcement behaviour in the laboratory of Dr Jocelyne Caboche and Dr Peter Vanhoutte at Université Pierre and Marie Curie, Paris. In 2014, Emma joined the laboratory of Prof Barry Everitt as a postdoctoral Research Associate in the Department of Psychology, at the University of Cambridge. There she started her projects on the mechanisms underlying aversive learning and memory in rodent models under the mentorship of Dr Amy Milton, and was awarded a Future Leaders Anniversary Fellowship from the BBSRC. In 2018, she was appointed as a temporary lecturer in the neighbouring Dept. of Physiology, Development and Neuroscience at Cambridge, and elected a Fellow of Murray Edwards College, where she was the Director of Studies for Psychology and the Executive Postgraduate Tutor. Emma took up a Lectureship in the School of Physiology, Pharmacology and Neuroscience at the University of Bristol in 2021. Her research continues to explore the mechanisms of memory, particularly memory of aversive events. Emma uses a combination of behaviour, pharmacology and biochemical methods that can address questions about which signalling proteins and receptors are crucial for the processing of memory in the brain. Currently, she focuses on a brain region called the amygdala to understand why a memory of a fearful event persists so strongly over time, and how it may potentially be dampened by interfering with specific neurochemical processes or by behavioural interventions."
- Dr Rochelle Ackerley, Aix-Marseille University, France
20 February 2023
The encoding of affective and emotional states in humans: how signals from the periphery are tuned to provide us with optimal sensory feedback
Abstract:
Affective and emotional processes have profound effects on our bodies. We need these mechanisms to engage in behaviours such as establishing inter-personal bonds and understanding how others feel, as well as processing the consequences of our actions. However, these processes are not just phenomena of the brain; affective signals are encoded from the skin and there is a direct descending influence of emotions on our body, from the muscles. I will present a series of studies that show evidence for these mechanisms from direct recordings from single nerve fibres in humans, via the technique of microneurography. Affective signals, such as pain and pleasantness, can be encoded directly by C-fibres. For pleasant, positive affective touch, C-tactile (CT) fibres have been shown to fire optimally to a slow, gentle caress delivered around skin temperature, which has linked them to inter-personal bonding. On the other hand, the descending gamma drive has been shown to influence muscle spindle sensitivity, where emotions can shape how movements are encoded, thus allowing us to prime our own reactions. Overall, I will cover how and why such affective and emotional processes are important in our lives and where future research may take us.
Bio:
Rochelle Ackerley is a permanent researcher with the CNRS in France and leads the SomatoSense group. Her research focuses on sensorimotor mechanisms, where she has specialised in the field of affective touch. She obtained her PhD in Physiology from the University of Bristol in 2006, then worked in industry. She completed post-docs at the University of Manchester, on eye-head movements, and at the University of Gothenburg in Sweden, where she learned the technique of microneurography (recording from human peripheral nerves). She moved to France in 2015 and gained an ERC Consolidator grant in 2017 to investigate complex mechanisms in touch, such as wetness perception. She is president of the International Association for the Study of Affective Touch (IASAT) and secretary for the Society for Microneurography.
- Dr Grace Lindsay New York University, US
20 February 2023
Exploring how recurrence helps visual processing using artificial neural networks
Abstract:
Behavioral studies have shown that visual perception of noisy or degraded images is enhanced when participants are given more time to process the image; this is believed to be due to the influence of recurrent connections in the visual system. I will share some work showing how recurrent connections can be added to convolutional neural networks, and how such recurrent networks can replicate trends from behavioral studies. I will furthermore demonstrate that the underlying computations the recurrence implements are different for different forms of recurrence, and I will briefly discuss the implications for experimental studies of the role of recurrence in visual processing.
Bio:
Dr Grace Lindsay is currently an Assistant Professor of Psychology and Data Science at New York University. She received her PhD at the Center for Theoretical Neuroscience at Columbia University in the lab of Ken Miller and went on to complete a Research Fellowship at the Gatsby Computational Neuroscience Unit at University College London. Her work uses artificial neural networks to understand the brain, with a particular interest in the control and effects of attention on sensory processing. She is also passionate about using machine learning to help tackle climate change. Last but not least, Grace is the author of the popular science book Models of the Mind where she talks about how and why we use mathematics to understand the brain.
- Prof David Wyllie, University of Edinburgh, UK
13 February 2023
Modelling fragile X syndrome with human iPSC-derived neurons: don’t ignore the glia
Abstract:
This seminar will focus on a key role that astrocytes play in ‘correcting’ aberrant action potential firing in human cortical neurons derived from pluripotent stem cells. I will outline a mechanism by which this cell non-autonomous regulation occurs and highlight the additional insights that can be gleaned from using human-based model systems to complement rodent-based model systems.
Bio:
David is the Director of the Centre for Discovery Brain Sciences and deputy-Dean of Biomedical Sciences at the University of Edinburgh. Since gaining his PhD from University College London in 1992 he began a long-standing research interest in physiology, pharmacology and function of ligand-gated ion channels, particularly those activated by the neurotransmitter, L-glutamate. Through electrophysiological studies, his lab seeks to understand the structure-function properties and physiological roles of the various subtypes of NMDA receptors. In related research he uses pre-clinical models of single gene causes of neurodevelopmental disorders to study the properties of altered synaptic function and to assess the extent to which pharmacological intervention can ameliorate the changes that are observed in such models. Currently, his research extends to the electrophysiological and functional characterization of defined neuronal and glial populations derived from human pluripotent stem cells and specifically those from individuals suffering from neurodevelopmental and neurodegenerative diseases. His overall aim is to develop an integrated approach to research that begins with the study of single protein molecules and synaptic function and extends, through collaboration with colleagues, to whole animal studies with an ultimate goal of the clinical study and treatment of disease.
- Dr Ingrid Reverte, Sapienza University, Italy
6 February 2023
The role of microglia in regulating experience-dependent plasticity
Abstract:
Microglia are dynamic cells, constantly surveying their surroundings and interacting with neurons and synapses. A wealth of knowledge has revealed a critical role of microglia in modulating synaptic transmission and plasticity in the developing brain. Recent evidence also suggest that microglia regulate synaptic plasticity in the adult brain. However, how microglia influence the normal functioning of synapses is still largely unknown. In this talk I will discuss our results regarding the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Besides, I will present new data on current projects exploring the role of microglia in modulating experience-dependent plasticity, in particular in the acquisition and maintenance of fear memories and in synaptic plasticity adaptations occurring during withdrawal from psychostimulants.
Bio:
Ingrid Reverte is an Assistant/Adjunct Professor (Physiology) at the Department of Physiology and Pharmacology of the Sapienza University of Rome. She started her career at the University Rovira i Virgili, Tarragona, Spain, where she obtained her B.Sc. in Psychology and defended her PhD in Neurobiology. She then moved to Brooklyn College, City University of New York, where she worked as a Postdoctoral Research Scientist and Adjunct Professor at the Department of Psychology.
- Dr Omar Perez, University of Chile, Chile
The reliability of value signals across the brain
30 January 2023
Abstract:
Extraction of relevant stimulus features from the dynamic sensory scene needs to be coupled to the execution of appropriate adaptive responses to ensure survival. A predator will need to evaluate its position with respect to that of moving prey, define an approach strategy and carry out the proper motor commands to execute it. The most efficient strategy will require an estimation of the future position of the target and should account for the predator’s sensorimotor processing delays to make a predictive interception. Mice can hunt moving prey and have been established as a successful model to study visually guided pursuit and capture behaviours. However, their ability to adapt their pursuit strategy to the direction of travel and speed of the target is poorly understood. To study this, we developed a new behavioural paradigm in which mice were trained to pursue and catch a moving target displayed on a touch screen. We ensured the performance of behaviourally consistent pursuit approaches by implementing a maze-like arena design and closed-loop stimuli presentation. Mice perform hundreds of trials per session and their interception success depends on the speed and contrast of the target. By modifying their running speed and the trajectory followed to reach the target, mice can adapt their pursuit strategy to the demands of the task. We are currently investigating the role of the superior colliculus in the tracking and interception of moving targets during pursuit behaviour..
Bio:
Flor obtained a degree in biological sciences at the University of Buenos Aires in 2009. She did her doctoral research with Angus Silver and Thomas Mrsic-Flogel at the department of Physiology, University College London (UCL). For postdoctoral training she first joined Sonja Hofer’s lab in the Biozentrum, Switzerland, and then moved to Andrew King's lab at Oxford University as a fellow from the Royal Commission for the Exhibition of 1851. In 2019 she started her lab in the Francis Crick Institute investigating the organization of the neuronal circuits responsible for integrating multisensory information and selecting behaviourally relevant targets."
- Dr Axel Montagne, University of Edinburgh, UK
Cerebrovascular and inflamm-ageing link to dementia
23 January 2023
Abstract:
Our brain is an energy-hungry organ surrounded by a rich network of blood vessels supplying the oxygen and nutrients required to function. It is essential that the microenvironment in the brain is finely controlled, and this is achieved through the specialist blood-brain barrier (BBB) structure. However, dysfunction of the BBB is recognised as one of the earliest events in the progression of brain disorders that cause dementia. We have previously discovered that one type of cell within the BBB, the pericyte, is particularly affected during disease and we aim to fully understand the consequences to the BBB and brain health as a whole. Using a combination of advanced molecular and imaging techniques including MRI, we seek to uncover the disease mechanisms at play and identify therapeutic targets for intervention. .
Bio:
Dr Axel Montagne joined the UK Dementia Research Institute at Edinburgh in December 2020. He completed his PhD degree at the University of Caen Normandy (France) in 2012, followed by postdoctoral training at the University of Southern California (USC) in Los Angeles from 2013 to 2016. Axel rapidly became Assistant then Associate Professor at USC in 2016 and 2020, respectively. His career has focused on how cerebrovascular dysfunctions contribute to neurodegeneration and dementia in both animal models and humans. In his UK DRI program, he combines molecular approaches with rodent non-invasive imaging, particularly MRI, PET, and two-photon microscopy, to study the causes and effects of blood-brain barrier (BBB) dysfunction, with a particular focus on the pericyte-endothelial crosstalk, in the context of neurodegenerative disease. Dr Montagne was recently awarded a prestigious MRC Career Development Award for his project “Interplay between brain endothelial cells and pericytes in brain health and disease”. He also received the SCOR Young European Researcher Prize for his research into Alzheimer’s disease. His talk focused on the preclinical and clinical evidence supporting the vascular contribution to dementia with an emphasis on early pericyte and BBB dysfunctions.