Archived list of the 2013 seminars & events at the Centre for Discovery Brain Sciences. January Learning to trust landmarks - sensory integration in the rodent head direction system Friday 18 January 2013, 1.30pm Prof Kate Jeffery (University College London) Abstract: “Knowledge” in the brain is built up from the convergence of sensory information from different sources, and a key task for cognitive neuroscientists is to understand how this information is pieced together. An ideal model system for this task is the head direction (HD) signal, which indicates which way an animal is facing: this signal arises from a convergence of external environmental cues and internal self-motion information, and is a paradigmatic case of sensory integration. In this talk I will present experiments with HD cells in which we examine how the cells learn to decide how much to “trust” a landmark. Two contrasting theoretical frameworks, attractor models and Bayesian integration models, make different predictions about how the system should make this decision. Our data from single neuron recordings made in awake, freely exploring animals support both possibilities and suggest a possible reconciliation of these two frameworks, possibly providing general principles for cue integration in sensory systems. Developing rat models of ASD for fundamental discovery and translational research Friday 25 January 2013, 1.30pm Dr Sally Till (Centre for Integrative Physiology) Mechanisms of excitotoxicity Friday 25 January 2013, 1.30pm Prof Giles Hardingham (Centre for Integrative Physiology) February Homeostasis in neural circuits: Is there a neural set point? Friday 8 February 2013, 1.30pm Dr Matthias Hennig (School of Informatics) Abstract: In recent years, a whole range of mechanisms have been discovered that modulate synapses and neural excitability in an activity-dependent manner after chronic changes in activity. Collectively termed homeostatic processes, they are thought to be responsible for maintaining stability and computational capabilities in neural circuits. While well characterised at a cellular level, relatively little is known about the effects of these processes in networks of neurons. I will summarise recent work investigating homeostasis in the developing retina and cultured neurons, and try to provide some tentative answers to the question posed above. Synaptic tagging and capture: in vitro curiosity or potential memory mechanism Friday 8 February 2013, 1.30pm Dr Stephen Martin (Centre for Cognitive and Neural Systems) Abstract: The neural mechanisms of long-term memory formation remain poorly understood. However, it is clear that certain memories - particularly those with high emotional or motivational significance - are destined for long-term storage, while others are rapidly forgotten. The phenomenon of synaptic tagging and capture, discovered over a decade ago, provides a possible mechanism for this selection process. Specifically, in isolated hippocampal slices, decaying long-term potentiation (LTP) of synaptic strength can be stabilized, and converted to late-LTP lasting many hours, by prior or subsequent strong high-frequency stimulation of an independent input to a common population of neurons. In this talk I will discuss our recent investigations of the synaptic tagging and capture phenomenon in the intact rat - a first step towards closing the gap between cellular studies of protein-synthesis-dependent synaptic potentiation and behavioural studies of memory persistence. Synaptic plasticity at mossy fibre synapses in the hippocampus Friday 15 February 2013, 1.30pm Dr Jack Mellor (University of Bristol) Abstract: Synaptic plasticity is thought to underlie learning and memory but is often studied using artificial induction paradigms. Jack Mellor's lab study the induction of synaptic plasticity in in vitro brain slices in response to patterns of activity recorded from behaving animals giving a greater understanding of the relevance of these much studied phenomena. The function of the brain depends not only on synapses and the Mellor lab also examine how these patterns of activity affect the intrinsic excitability of neurons. Finally they study the role of glutamate receptor trafficking in synaptic plasticity using genetic modifications of specific neurons within hippocampal slices. Sensorimotor processing in the awake cortex Friday 22 February 2013, 1.30pm Ian Duguid (Centre for Integrative Physiology) Abstract: The primary motor cortex (M1) plays a pivotal role in the initiation and control of complex motor movements. Although we are beginning to understand the patterns of motor cortex activity that occur when humans or animals are engaged in specific motor behaviours, we still know very little about the mechanisms that underlie motor command generation. What are the spatiotemporal patterns of synaptic input that motor cortex neurons receive during behaviour? How are these inputs integrated to generate specific output spike patterns? How does brain state affect sensorimotor processing in M1? During this talk, I will discuss some of our recent findings that suggest M1 output neurons can be functionally classified into two distinct subgroups depending on: subthreshold membrane potential dynamics; synaptic input structure; firing rates; and movement-related changes in input sensitivity. Elucidating mechanisms of plasticity in myelination using zebrafish Friday 22 February 2013, 1.30pm David Lyons (Centre for Neuroregeneration) Abstract: It has recently been shown that central nervous system myelination is highly dynamic, continues into adult life and can be regulated by environmental cues. The number of myelin sheaths made by individual oligodendrocytes is a key parameter by which the extent of myelination can be regulated and it is now clear that this number can change depending on the local cellular environment, and also on the social environment of the animal.It is unclear, however, how plasticity in myelin sheath number is manifest in vivo over time. During this talk, I will describe our recent work in zebrafish which makes use of their amenability for live cell imaging to observe myelination by oligodendrocytes in the living animal over time. I will also document a role for a key signalling molecule in regulating the extent of myelination, and provide preliminary data related to our searches for additional molecular mechanisms that regulate CNS myelination in vivo. March Control of neuronal Ca2+ signalling by AMP-activated protein kinase and Bcl-2 family proteins Friday 1 March 2013, 1.30pm Professor Jochen Prehn (Royal College of Surgeons, Ireland) Abstract: Professor Prehn's research has focused on cell death mechanisms and their implication for human disease. Apoptosis is critical for the elimination of unwanted cells during development. Defects in apoptosis pathways have been implicated in neurodegeneration, diabetes mellitus, ischemic injury, and malignant disorders. Prof Prehn has successfully conducted research in these four areas with a particular emphasis on bioenergetics, mitochondrial physiology, Bcl-2 family proteins and AMPK signalling. A second major research interest lies in real-time imaging of cell death signals in neurons and cancer cells, employing confocal and in vivo imaging techniques. This research includes the development of computational approaches to understand and overcome apoptosis sensitivity and resistance and cellular bioenergetics at a systems rather than single entity level. Control of spinal neurogenesis in the zebrafish Friday 8 March 2013, 1.30pm Dr Catherina Becker (Centre for Neuroregeneration) Abstract: Motor neurons are the cells in the spinal cord that control all skeletal muscle movement. In zebrafish, all motor neurons are born within the first 54 hours post fertilization, when the larvae are still translucent and amenable to drug and genetic manipulation. In post-embryonic and adult fish, motor neurons are regenerated upon a spinal injury or extensive motor neuron death, by the reactivation of spinal progenitor cells. We are investigating the molecular mechanisms of motor neuron development and regeneration from these progenitors. VAP proteins and neurodegeneration Friday 8 March 2013, 1.30pm Dr Paul Skehel (Centre for Integrative Physiology) Abstract: Mutations in the VAPB gene are associated with a very rare inherited form of Amyotrophic Lateral Sclerosis, ALS8. The protein is expressed ubiquitously and it appears to function as a docking protein on the surface of the endoplasmic reticulum where it mediates interaction with microtubules, lipid transport proteins and mitochondria. The disease-associated mutation leads to the formation of insoluble intracellular protein aggregates, but how this influences function leading to a late on-set pathogenesis is not yet understood. Adaptors and clathrin-mediated traffic at the synapse Friday 15 March 2013, 1.30pm Dr Stephen Royle (University of Warwick) Abstract: The Royle lab has a joint interest in membrane traffic and mitosis. Dr Royle investigates the role of proteins that are usually involved in vesicle endocytosis but also "moonlights" with functional roles in mitosis. He uses a range of techniques from molecular biology/biochemsitry/to live cell imaging of both mitosis and endocytosis in primary neuronal cultures. A key interest of the lab is how clathrin controls the mitotic process, and he has published a range of high impact papers on this topic over the past few years. Chromatin folding in development and disease: Is what you 'C' what you see? Friday 22 March 2013, 1.30pm Prof Wendy Bickmore (School of Molecular, Genetic and Population Health Sciences) Glucocorticoids - inflammation and heartbreak Friday 22 March 2013, 1.30pm Prof Karen Chapman (Centre for Cardiovascular Science) Abstract: We investigate 2 aspects of glucocorticoid action - firstly, the role of glucocorticoid metabolism (by the enzyme 11beta-hydroxysteroid dehydrogenase) in modulating glucocorticoid action, particularly during inflammation and secondly, the role of glucocorticoids in fetal heart maturation and how this programmes adult heart function. To address these questions, we use mice with global or conditional disruption of the gene encoding 11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor (GR) focusing on the macrophage, adipocyte, liver and cardiomyocytes/vascular smooth muscle. April The Delhi-Edinburgh Lecture Series Students and staff are invited to join innovative live-streamed collaborative learning sessions, exploring topics of mutual interest at University of Edinburgh and University of Delhi. 12:00 - 13:00, Wednesday 3rd April Population: how much of a problem? Prof Roger Jeffery, University of Edinburgh 12:00 - 13:00, Monday 22nd April Reading Indian Literature: Reading Ourselves. Prof Harish Trivedi, University of Delhi Venue: Edinburgh Centre for Carbon Innovation, 15 South College Street. The Delhi-Edinburgh Lecture Series Alpha2-chimaerin in development and disorders of the ocular motor system Friday 5 April 2013, 12.30pm Prof Sarah Guthrie (King's College London) Abstract: The signalling protein alpha2-chimaerin plays a crucial role during axon guidance in the vertebrate ocular motor system. Defects in the development of this system lead to eye movement disorders in humans, and mutations in alpha2-chimaerin are causal in Duane retraction syndrome. Our work seeks to understand the role played by alpha2-chimaerin, its upstream regulators and downstream signalling components in both normal and abnormal ocular motor development, focussing on the chick and zebrafish model systems. Seasonal breeding and photoperiodic time measurement in birds Friday 26 April 2013, 12.30pm Dr Simone Meddle (Roslin Institute) How do chemotherapeutic agents damage the ovary? Friday 26 April 2013, 12.30pm Dr Norah Spears (Centre for Integrative Physiology) Abstract: It has long been recognised that chemotherapy treatment can result in fertility problems in patients, in particular leading to premature ovarian failure in premenopausal females, and to loss of viable sperm particularly in pre-pubertal boys. The precise manner by which the drugs damage the gonads is, however, much less clear, yet without that information, protective treatments will be difficult to develop. We are using mouse gonadal tissue culture techniques to examine the effect of drugs commonly administered to younger cancer patients. For the ovary, our work shows that each drug leads to a very different pattern of damage, acting through different cellular mechanisms. This may in turn mean that any treatments designed to protect the ovary from chemotherapy-induced damage have to be tailored to the specific drug regimens used. To date, preliminary work on the testis indicates chemotherapy drugs directly damage germ cells before damage to the rest of the testis becomes apparent. Constant Cravings: Does Food Addiction Exist ? Dr John Menzies will be talking about food addiction on the Radio 4 programme Constant Cravings. The show will be broadcast on Thursday 30th April 2013 at 20:00 and on Sunday 5th May at 17:00. John has also just published an article 'Can stress make you fat?' in The Skeptic magazine. Constant Cravings on BBC iPlayer May Role of synaptophysin in synaptic vesicle recycling - implications for X-linked intellectual disability Friday 3 May 2013, 12.30pm Dr Sarah Gordon (Centre for Integrative Physiology) Abstract: Synaptophysin (SYP) is a major synaptic vesicle protein whose function remains unknown. SYP knockout mice display mild deficits in learning and memory, but no global defects in synaptic transmission. A recent study identified four separate mutations in the SYP gene in families displaying X-linked intellectual disability (XLID). We investigated the function of SYP, and found that it is required for the retrieval of specific synaptic vesicle protein cargo from the plasma membrane during endocytosis, and XLID mutant variants of SYP are functionally defective in this process. These studies suggest that the efficient retrieval of protein cargo by SYP may be key to maintaining synaptic health. The utility of proteomics in the study of cerebrovascular dysfunction: relevance to ageing and Alzheimer's disease Friday 3 May 2013, 12.30pm Dr Luke Searcy (Centre for Cognitive and Neural Systems) Abstract: Cerebrovascular dysfunction is associated with both ageing and Alzheimer’s disease. The structural integrity of the cerebrovasculature is altered during aging and these changes can be accelerated by vascular pathologies, most notably cerebral amyloid angiopathy . To better understand how cerebral vessels globally respond to both age and accumulating Aβ, we have used quantitative label-free proteomics to investigate the proteomic signatures of vessel-enriched fractions from the brains of WT and Tg-SwDI mice at 3 and 9 months of age. Our vascular-focused approach has revealed distinctly different protein expression patterns as a result of age in the presence of microvascular Aβ accumulation. Such techniques can be useful in discovering novel protein changes in very specific pools and act to generate new hypotheses for further research. GABAA receptor membrane dynamics and the tuning of inhibitory transmission Friday 10 May 2013, 12.30pm Dr Josef Kittler (University College London) Gastric inhibitory peptide (GIP) and the vasculature: A reminder of the central role of the gut in the pathophysiolgy of T2D and its complications Friday 17 May 2013, 12.30pm Dr Maria Gomez (Lund University, Sweden) August Anatomical and functional segregation within the central oxytocin system Friday 9 August 2013, 12.30pm Dr Valery Grinevich (University of Heidelburg) Abstract: Oxytocin (OT), the neuropeptide of sociality and reproduction, is expressed in parvo- and magnocellular neurons localized in the hypothalamic paraventricular nucleus (PVN), while supraoptic (SON) and accessory nuclei are composed by magnocellular OT neurons. Magnocellular OT neurons were known as the major source for OT in the blood. However, our recent data obtained by cell specific viral vectors demonstrate that magnocellular OT neurons innervate major forebrain regions thereby allowing targeted action and, this way, holding an importance for the behavioral effects of OT. Furthermore, to probe the functionality of those forebrain innervating axons, optogenetic stimulation (e.g. in the central amygdala) was applied to elicit behavioral effects by targeted OT release. The new notion implies the need for refinement of the previous allocation in which magnocellular neurons exert only systemic OT actions and, respectively, parvocellular neurons impact solely the central actions of OT. The plethora of behavioral OT effects in distinct forebrain regions suggests furthermore a functional and anatomical segregation of magnocellular OT neurons. Using retrograde tracing and the 'virus-mediated genetic activity-induced tagging' (vGAIT) we could show that magnocellular OT neurons which innervate different forebrain regions are (in most cases) situated distinct from each other. Similarly, the topographical and functional segregation occurs in parvocellular OT cells as viral-based tracing and in vivo optogenetics revealed a new subgroup of parvocellular OT cells in the PVN that synapses on magnocellular SON OT neurons and simultaneously projects to the brainstem. This cell group provides the neuroanatomical basis for concerted activity of the OT system potentially important for an efficient milk let down on one side (magnocellular OT neurons) and specific maternal behaviors (parvocellular OT neurons) on the other side. The here presented data indicate a high degree of specialization of parvo- and magnocellular OT neurons, opening the possibility for dissecting OT circuits specific for distinct forms of behaviors varying from fear to empathy. September Transgenic dissection of the interactions between the hippocampus and entorhinal cortex Monday 2 September 2013, 12.30pm Cliff Kentros (University of Oregon) October UnPICKing actin filaments in brain cells: Dynamic regulation of trafficking and morphology in neurons and astrocytes Friday 4 October 2013, 12.30pm Dr John Hanley (Bristol University) A rat model of snacking: how much condensed milk is enough? Friday 11 October 2013, 12.30pm Dr John Menzies (Centre for Integrative Physiology) Abstract: The widespread availability of inexpensive, energy-dense food has resulted in a massive strain on health. Commonly, weight gain is blamed on an inability to resist the temptation of palatable snacks, which can be high in fat, high in sugar or both. It is perceived that snacking can represent a small but regular addition to daily energy intake, and that this could result in a long term increase in body weight. However, there is little evidence for a positive relationship between levels of snacking and obesity in humans. Despite the often poor nutritional content of high-sugar and high-fat snack foods, compensatory responses, such as a decrease in intake of other foods, may mitigate against these short-term spikes in energy intake. In other words, hedonically driven eating may be counterbalanced by homeostatic mechanisms. Here I will describe a rat model of hedonically-driven snacking using condensed milk as a reward. I will show the behavioural effects of this reward paradigm, and its effects on neural activation in the hypothalamus and other regions. When Pax6 meets cell cycle Friday 11 October 2013, 12.30pm Dr Da Mi (Centre for Integrative Physiology) Revisiting the multiple origins of Cajal-Retzius cells Monday 21 October 2013, 12.30pm Dr Alfonso Fairen (Institute for Neuroscience, Alicante, Spain) Abstract: Brain function depends on the ordered integration of neurons into microcircuits during development. In the group, we use the cerebral cortex, the hippocampal formation and the olfactory bulb as models. We perform detailed neuroanatomical analyses of circuits, focusing on neural circuit assembly along development. We are also interested in ascertaining how developmental alterations of certain populations of neurons and their axonal systems in genetically modified mice influence the functional organization of the adult brain, and how this in turn influences behavior. Additionally, we are interested in establishing suitable mouse models of human mental diseases. But Drosophila don't even have lungs!: An unexpected model for the disease Primary Ciliary Dyskinesia Friday 25 October 2013, 12.30pm Prof Andrew Jarman (Centre for Integrative Physiology) Tissue-specific nuclear envelope proteins contribute to differentiation by influencing gene expression through spatial organisation of the genome Friday 25 October 2013, 12.30pm Dr Eric Schirmer (Centre for Integrative Physiology) Abstract: Spatial genome organization is thought to contribute to the regulation of gene expression; however, little is known about how spatial patterns are established or how/why they affect gene expression. We have identified several nuclear envelope transmembrane proteins (NETs) that each increased peripheral incidence of specific subsets of chromosomes. Strikingly, these NETs were highly tissue-specific; thus effects were further investigated in cell types matched to the tissues where each NET is expressed. Investigations in liver, fat and muscle differentiation support the hypothesis that tissue-specific NETs reposition genes to the periphery to promote better repression of alternative differentiation pathways. November Growth, Inflammation and the Brain Friday 15 November 2013, 1.30pm Dr Andrew Jackson (Institute of Genetics and Molecular Medicine, Western General) Transcriptional and epigenetic regulation of lineage identity in neural stem cells and brain cancer Friday 15 November 2013, 1.30pm Dr Steve Pollard (University College/ Centre for Integrative Physiology) Brain circuits coordination appetite Friday 22 November 2013, 1.30pm Prof Lora Heisler (Metabolic Research Laboratories, University of Cambridge) Evolution of cerebral cortical development Friday 29 November 2013, 1.30pm Abstract: Comparative developmental studies of the mammalian brain identify key changes that might have generated the diverse structure and function of this organ. The radial and tangential enlargement of the cortex was driven by changes in the cortical neurogenesis, in particular the elaboration and cytoarchitectonic compartmentalization of the germinal zone, with alterations in the proportions of various progenitor types. Some cortical cell populations arrive to the cortex through tangential migration to converge in a specific area where the various cell populations organize themselves into precise neuronal circuits. Comparative analysis of the similarities and variation in these neurogenetic and migration patterns, together with the analysis of gene expression patterns hold the key to reveal conserved, diverged or converged development. A number of recent studies have begun to characterize the chick, mouse, human and non-human primate cortical transcriptome to understand how gene expression relates to the development, anatomical and functional organization of the neocortex. December Ancient behavioral modulation by oxytocin/vasopressin-related peptides Friday 6 December 2013, 1.30pm Dr Isabel Beets (Department of Biology, Leuven, Belgium) Abstract: Neuropeptidergic signaling plays an important role in modulating the behavioral output of neuronal circuits according to environmental and internal state cues. This potential for modulation is supported by the diversity of neuropeptides and their receptors that, however, often show strong evolutionary conservation. In mammals, neuropeptides of the oxytocin and vasopressin family are key modulators of social behavior and cognitive processes, but the evolutionary origin of these effects remains elusive. We have characterized a related signaling system and its neuromodulatory function in the nematode C. elegans, and shed light on the underlying cellular and molecular circuit. In the worm, oxytocin/vasopressin-related signaling regulates associative learning, suggesting that this peptide family is an ancient modulator of neural circuits underlying behavioral plasticity. Ventromedial nucleus of the hypothalamus (VMH) projecting lateral parabrachial (LPBN) cholecystokinin neurons regulate glucose homeostasis Wednesday 11 December 2013, 1.08pm Dr Al Garfield (CIP/ Harvard) Abstract: The lateral parabrachial nucleus (LPBN) forms part of an assimilatory forebrain-projecting viscerosensory relay that subserves physiological and behavioural responses to a number of viseroceptive modalities, including nociceptive processing, thermostasis, malaise, energy homeostasis and metabolism. As an archetypal visceral stressor, hypoglycaemia is known to induce neural activity within the LPBN, yet a definitive function for the LPBN within this context remains to be determined. Here we identify cholecystokinin (CCK) expressing neurons as the cellular basis for LPBN mediated glucoregulation. Specifically, LPBN CCK neurons are reactive to states of glucoprivation and are able to promote elevations in blood glucose levels when artificially stimulated. Furthermore, we find that via a specific LPBN ? ventromedial nucleus of the hypothalamus (VMH) microcircuit these CCK neurons form part of the counter-regulatory machinery required for physiological responses to hypoglycaemia. This article was published on 2022-10-17
