Chairs
Professor Alexej Verkhratsky, University of Manchester, UK
Professor Alexej Verkhratsky, University of Manchester, UK
Professor Alexei Verkhratsky, MD, PhD, D.Sc., Member of Academia Europaea, Member of the German National Academy of Sciences Leopoldina, Member of Real Academia Nacional de Farmacia of Spain, was born in 1961 in Stanislaw, Galicia, Western Ukraine. Currently Alexei is Professor of Neurophysiology in the faculty of Life Sciences at the Mniversity of Manchester. In 2007 to 2010 he was a visitor professor/Head of Department of Cellular and Molecular Neurophysiology at the Institute of Experimental Medicine in Prague; he also serves as a Research Professor of the Basque Research Council, Bilbao and Adjunct Scientific Director of the Achucarro Basque Center for Neuroscience; from 2011 he is as a Honorary Visitor Professor at Kyushu University, Fukuoka, Japan. Alexei is the editor-in-chief of Cell Calcium, Receiving Editor of Cell Death & Disease and member of editorial boards of many journals.
Alexei Verkhratsky is an internationally recognised scholar in the field of cellular neurophysiology. His research is concentrated on the mechanisms of inter- and intracellular signalling in the CNS, being especially focused on two main types of neural cells, on neurones and neuroglia. In recent years he studies the glial pathology in Alzheimer disease. He authored a pioneering hypothesis of astroglial atrophy as a mechanism of neurodegeneration.
Scientometry:
Prof Verkhratsky authored and edited 12 books and published ~ 350 papers and chapters. His papers were cited >12000 times, H-index 64 (ISI, 04/2015).
09:00-09:30
P2X receptors
Emeritus Professor Alan North FRS, University of Manchester, UK
Abstract
P2X and P2Y receptors were distinguished by Burnstock & Kennedy (1985) on the basis of differential actions of ATP analogs, notably ab-methylene-ATP and 2-methythio-ATP. P2Y receptors were involved in relaxation of intestinal smooth muscle, whereas P2X receptors were responsible for contraction of smooth muscle of the bladder and vas deferens. The eight P2Y receptors (numbered 1, 2, 4, 6, 11, 12, 13 and 14) are class A G-protein coupled receptors activated by ATP, ADP or UTP.
P2X receptors are trimeric membrane proteins that form cation channels activated by ATP. The seven P2X receptor genes in mammals encode proteins with intracellular N- and C-termini, and two membrane spanning domains separated by a large extracellular domain: channels form as homomers (numbered 1, 2, 3, 4, 5, 7) or heteromers (2/3, 1/5). In overall topology and subunit assembly, P2X receptors resemble acid-sensing ion channels (ASIC) and epithelial sodium channels (ENaC)(Browne et al. 2010; Baconguis et al 2013). The structures of the closed and open zebrafish P2X4 receptor (at 2.9 A: Hattori & Gouaux, 2012) are completely consistent with previous studies based on functional expression and site-directed mutagenesis (Browne et al 2010). They are also supported by more recent work using disulfide locking (Stelmashenko et al. 2014), gating by lipohilic attachment (Rothwell et al 2014) and gating by light using an attached bis(maleimido)azobenzene (Browne et al 2014).
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Emeritus Professor Alan North FRS, University of Manchester, UK
Emeritus Professor Alan North FRS, University of Manchester, UK
(Richard) Alan North graduated in physiology (BSc 1969), medicine (MB ChB 1969) and pharmacology (PhD 1973) from the University of Aberdeen. After briefly working as a physician, Professor North held appointments as Associate Professor of Pharmacology at Loyola University Stritch School of Medicine in Chicago, Professor of Neuropharmacology at the Massachusetts Institute of Technology, Senior Scientist and Professor of Neurology at the Vollum Institute of Oregon Health Sciences University, Principal Scientist at the Geneva Biomedical Research Institute (a division of GlaxoWellcome Research and Development in Switzerland), and Professor of Molecular Physiology at the University of Sheffield.
He joined the University of Manchester as Vice-President in 2004, serving as Dean of its Faculty of Life Sciences (2004 to 2008), Dean of its Faculty of Medical and Human Sciences (2006-2011) and he was the founding Director of the Manchester Academic Health Science Centre (2008-2010). From late 2013, he has been Emeritus Professor at the University of Manchester.
His research contributions have been in the understanding of the ionic mechanisms involved in the actions of neurotransmitters and drugs (particularly opiates), and in the molecular physiology of extracellular of adenosine triphosphate acting at P2X receptors. He was Editor-in-Chief of the British Journal of Pharmacology as well as serving two terms as an editor of The Journal of Physiology. He was President of The Physiological Society from 2001-2004. He served on the Medical Research Council, and chaired several of its review committees. Alan is a Fellow of the Royal Society, the Royal College of Physicians, the Academy of Medical Sciences, and Academia Europae, and holds Honorary Membership of The Physiological Society and the British Pharmacological Society.
09:45-10:15
The glymphatic system
Professor Maiken Nedergaard, Københavns University, Denmark
Abstract
We have recently described a macroscopic pathway in the central nervous system – the glymphatic system that facilitates the clearance of interstitial waste products from neuronal metabolism. Glymphatic clearance of macromolecules is driven by cerebrospinal fluid (CSF) that flows in along para-arterial spaces and through the brain parenchyma via support from astroglial aquaporin-4 water channels. The glymphatic circulation constitutes a complete anatomical pathway; para-arterial CSF exchanges with the interstitial fluid, solutes collect along para-venous spaces, then drain into the vessels of the lymphatic system for ultimate excretion from the kidney or degradation in the liver. As such, the glymphatic system represents a novel and unexplored target for prevention and treatment of neurodegenerative diseases.
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Professor Maiken Nedergaard, Københavns University, Denmark
Professor Maiken Nedergaard, Københavns University, Denmark
Dr Nedergaard is Professor of Neurosurgery and Co-Director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) in Rochester, NY. She is also Professor of Glial Cell Biology and Co-Director of the Center for Translational Neuroscience at the University of Copenhagen, Denmark. Her multiple interests range from basic research on neuron-glia interactions to their role in aging, small vessel disease, seizure disorders and cerebral blood flow. Forefront amongst her discovery is the identification of the glymphatic system, a brain equivalent of the lymphatic system within which cerebrospinal fluid diffuses rapidly and mixes with interstitial fluids, thereby filtering metabolic byproducts that accumulate due to neuronal activity. Most recently, she published a landmark study in Science showing that the glymphatic system dramatically expands during sleep compared to waking – brain cleaning and detoxification is thus greatly facilitated during sleep, providing a novel and direct explanation for what we all generally consider sleep’s restorative effect.
11:00-11:30
Calcium-dependent memory traces in neurons and glia
Professor Arthur Konnerth, Technische Universitaet Muenchen, Germany
Abstract
The accumulation of amyloid-beta in the brain is an essential feature of Alzheimer’s disease (AD). However, the impact of amyloid-beta-accumulation on the dysfunction of neurons and circuits in vivo is still poorly understood. The neurodegeneration observed in AD has been initially associated with a progressive decrease in neuronal activity. Instead, in a mouse model of amyloidosis, we demonstrated that a substantial fraction of cortical neurons exhibit a massive increase in neuronal activity. These “hyperactive” neurons were located predominantly near the plaques of amyloid beta (Abeta)-depositing mice. In the visual cortex of the same mouse model, we found a progressive deterioration of sensory integration that paralleled the age-dependent increase of the amyloid-beta load. Remarkably, in the hippocampus of young mice, we observed a selective increase in hyperactive neurons before the formation of plaques, suggesting that soluble species of Abeta may underlie the impaired neuronal activity. In support of this model, we found that the acute treatment of transgenic mice with a gamma-secretase inhibitor reduced soluble Abeta levels and rescued the neuronal dysfunction. Recently, we discovered an Abeta-dependent impairment of slow-wave propagation, which causes a breakdown of the characteristic long-range coherence of slow-wave activity in the mammalian brain. We demonstrated that this impairment can be rescued by enhancing GABAAergic inhibition and, thereby, reducing the level of hyperactivity. Together, our results support the notion that neuronal hyperactivity is a major cellular mechanism underlying circuit dysfunction in AD.
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Professor Arthur Konnerth, Technische Universitaet Muenchen, Germany
Professor Arthur Konnerth, Technische Universitaet Muenchen, Germany
Arthur Konnerth is currently the Friedrich-Schiedel-Chair of Neuroscience and Director of the Institute for Neuroscience at the Technical University Munich. He is a member of the German National Academy of Sciences Leopoldina, the Academia Europaea and the Bavarian Academy of Sciences. His current research is focused on the development and application of methods that allow a quantitative understanding of function and dysfunction of neurons and circuits in the intact brain. A major goal is a better understanding of the cellular and circuit mechanisms of learning and memory in the healthy brain, as well as the pathophysiology underlying the impairment of cognition and memory in Alzheimer’s disease.
11:45-12:15
Regulation of neuronal calcium channel trafficking, subcellular localisation and function by auxiliary subunits
Professor Annette C Dolphin FRS, University College London, UK
Abstract
Voltage-gated calcium channels are essential for the function of all excitable cells, since they link changes in excitation to entry of Ca2+ into the cells. The effects of Ca2+ in neurons include neurotransmitter release, and changes in gene expression. The CaV2 family of calcium channels mediate neurotransmitter release and are strongly expressed in presynaptic terminals. I will address the interplay between the function of neuronal calcium channels and the role of their auxiliary subunits, particularly α2δ, in excitable cells, and describe what happens when the channels undergo aberrant trafficking. There is increasing evidence that voltage-gated calcium channel dysfunction is involved in a number of disorders, including the development of chronic pain, a major source of morbidity in the population. In experimental models of chronic neuropathic pain, in which the peripheral axons of sensory dorsal root ganglion neurons are damaged, the auxiliary α2δ-1 subunit is upregulated strongly in the damaged neurons. In my presentation, I will discuss the role of the auxiliary α2δ subunits in calcium channel trafficking and function, in both cell lines and in neurons from wild-type and α2δ-1 knockout mice. I will also relate this to changes in channel distribution that occur in neuropathic pain.
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Professor Annette C Dolphin FRS, University College London, UK
Professor Annette C Dolphin FRS, University College London, UK
Professor Annette C. Dolphin received her BA in Natural Sciences (Biochemistry) from the University of Oxford and her PhD at the Institute of Psychiatry in London. She held postdoctoral fellowships at the College de France in Paris, and at Yale University, before returning to a post at the National Institute for Medical Research. She then took up a lectureship at St. George's Hospital Medical School, London, and was appointed to the chair of Pharmacology at the Royal Free Hospital School of Medicine, London, in 1990. Following the merger of this Department with the UCL Department in 1997, she moved to the UCL campus. She was elected to the Academy of Medical Sciences in 1999. She has received several prizes including the Sandoz Prize of the British Pharmacological Society (1986), Pfizer Prize in Biology (1991) and the G.L.Brown Prize of the Physiological Society (1994). 1st Julius Axelrod Distinguished Lecturer in Neuroscience, Toronto (2000), Gary Price memorial lecturer of British Pharmacological Society (2011). She is currently an Editor of Pharmacological Reviews.