Chairs
Dr Clare Howarth, University of Sheffield, UK
Dr Clare Howarth, University of Sheffield, UK
Clare undertook a PhD at University College London on the Wellcome Trust 4 year PhD program in Neuroscience. Working with David Attwell, she discovered a new mechanism for the control of brain blood flow at the capillary level and produced the first energy budget for the cerebellum. Following her PhD, she was awarded a Sir Henry Wellcome Postdoctoral Fellowship which enabled her to work with Brian MacVicar (University of British Columbia), applying two-photon microscopy to brain slices, and with Nicola Sibson (Oxford), using in vivo MRI and optical imaging techniques to elucidate the role of astrocytes in regulating cerebral blood flow responses to hypercapnia. In October 2013 she moved to the University of Sheffield, where she was recently awarded a Sir Henry Dale Fellowship by the Wellcome Trust and Royal Society to investigate the role of astrocytes in neurovascular coupling in health and aging.
09:00-09:30
Balancing the brain’s energy supply: neurovascular coupling in the cortex and hippocampus
Dr Kira Shaw, University of Sussex
Abstract
Neurovascular coupling has been predominantly studied in primary sensory cortices, where neuronal activation leads to increased cerebral blood flow and a large influx of oxygenated blood. However, neural activity may be less well-coupled to increased blood flow in other brain areas. For example, local field potentials are highly correlated with fMRI/BOLD signals in sensory cortex, but not in the hippocampus (Ekstrom, 2010), suggesting neurovascular coupling may differ between sensory cortex and hippocampus. To investigate this directly, Dr Hall and her team used 2-photon imaging to record fluctuations in neuronal activity and microvascular diameter in primary visual cortex (V1) and the hippocampus of awake, behaving mice, as well as combined laser doppler flowmetry and haemoglobin spectroscopy to record baseline and stimulus-induced alterations in macroscopic haemodynamics. Compared to V1, the hippocampus had lower resting blood flow and blood oxygen saturation, despite similar rates of oxygen consumption. Furthermore, individual blood vessels dilated significantly less frequently and to a smaller extent in the hippocampus compared to V1, despite equivalent-sized calcium responses. Finally, increases in regional oxygen consumption led to smaller macroscopic increases in blood flow in the hippocampus compared to V1. These data suggest that not only is the hippocampus under-supplied with oxygen compared to primary sensory cortex at rest, but it is also less able to increase local blood flow in response to increased neuronal activity. These deficits in neurovascular coupling could contribute to the vulnerability of the hippocampus to hypoxia by reducing the ability of hippocampal neurons to match energy supply with demand.
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Dr Kira Shaw, University of Sussex
Dr Kira Shaw, University of Sussex
Kira Shaw is interested in the supply and regulation of energy in the brain (neurovascular coupling) across different brain states and regions. During her PhD (with Jason Berwick, University of Sheffield), she studied how neurovascular coupling relationships are altered by arousal levels (in awake mice, i.e. aroused/locomotion and quiescent/rest) or anaesthesia. In her current position as a post-doctoral researcher (with Catherine Hall, University of Sussex) she compares how the brain’s control of blood flow may differ between cortex and hippocampus, and how this might impact upon brain function.
09:45-10:15
Building a mathematical model of brain energy metabolism
Professor Renaud Jolivet, University of Geneva and CERN, Switzerland
Abstract
The brain consumes an inordinate amount of energy with respect to its weight. Understanding brain energy metabolism is crucial as numerous studies point to a metabolic component in various neurodegenerative disorders and because energetic considerations might have played an important role during evolution, constraining behaviour and providing a powerful explanation of certain cellular features as trade-offs between performance in information processing and energy savings. Professor Jolivet will briefly discuss these points before describing how to design models of brain energy metabolism and neurovascular coupling, the importance of calibration due to the multicellular complexity of the brain and algorithmic tools to analyse the behaviour of such models. The brain consumes an inordinate amount of energy with respect to its weight. Understanding brain energy metabolism is crucial as numerous studies point to a metabolic component in various neurodegenerative disorders and because energetic considerations might have played an important role during evolution, constraining behaviour and providing a powerful explanation of certain cellular features as trade-offs between performance in information processing and energy savings. Professor Jolivet will briefly discuss these points before describing how to design models of brain energy metabolism and neurovascular coupling, the importance of calibration due to the multicellular complexity of the brain and algorithmic tools to analyse the behaviour of such models.
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Professor Renaud Jolivet, University of Geneva and CERN, Switzerland
Professor Renaud Jolivet, University of Geneva and CERN, Switzerland
Renaud Jolivet studied theoretical biophysics at the University of Lausanne (1996-2001) before doing a PhD in computational neuroscience at École polytechnique fédérale de Lausanne in Lausanne, Switzerland (2001-2005). After his doctoral studies, he was a postdoc in Lausanne (2006-2007) and a fellow in Tokyo, Zürich and London (2007-2015). Since 2016, he is Joint Titular Professor in Medical Physics at CERN and at the University of Geneva, Switzerland. His main interest lies in the organization of brain energy metabolism and in the relation between energy consumption and information processing in neural networks, which his team studies in both experiments and computational models. He also holds a particular interest in the non-neuronal cells of the brain.
11:00-11:30
Neuronal activity and neuroenergetics with and without CBF
Dr Anna Devor, University of California, San Diego, USA
Abstract
Neurons in the brain rely on blood vessels for supply of oxygen and glucose. An increase in neuronal activity normally leads to vasodilation increasing cerebral blood flow (CBF), so that supply meets demand. Dilation is driven by multiple mechanisms emphasising its importance for healthy brain function. Vasoactive messengers are released by different types of neurons and possibly glia. In addition, blood vessels are endowed with an array of ion channels that propagate the signal along their walls ensuring “upstream” dilation magnifying the CBF response. But what happens to the oxygen and glucose? According to standard textbooks, brain’s energy is produced mostly by the oxidation of glucose to carbon dioxide and water. This notion is based on observations that cortical neuronal activity is lost within ~15 seconds of CBF interruption. A paradox that challenges this paradigm comes from Positron Emission Tomography studies, where glucose consumption was shown to exceed the oxygen consumption predicted by the stoichiometry of complete aerobic oxidation. Most of the brain’s grey matter energy is used to restore neuronal membrane potential that involves moving ions across against their concentration gradients. Therefore, Dr Devor and her team asked whether the ability of neurons to repolarise was lost within seconds of CBF interruption. Cortical neurons in the mouse brain, when repeatedly depolarised via light-controlled ion channels, continued to restore their membrane potential for over 20 minutes after a cardiac arrest. This observation suggests that neurons can utilise oxygen-independent mechanisms such as glycolysis, possibly not only upon asphyxia but also under normal physiological conditions.
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Dr Anna Devor, University of California, San Diego, USA
Dr Anna Devor, University of California, San Diego, USA
Anna Devor holds two academic appointments as Associate Adjunct Professor in Neurosciences and Radiology at University of California San Diego (UCSD) and Instructor in Radiology at Massachusetts General Hospital (MGH, Harvard Medical School). Dr Devor has a broad base of knowledge in cellular and systems-level neuroscience. Her secondary expertise is development and refinement of microscopic optical technology for imaging of brain activity in live animals (in vivo).
Dr Devor received her initial research training at the interface between experimental and computational neuroscience at Hebrew University of Jerusalem, Israel. Her PhD thesis focused on biophysical mechanisms of the membrane potential oscillations in a network of electrically coupled neurons. After completing her PhD in 2001, she went on to specialise in optical and MR-based imaging technology at Martinos Center for Biomedical Imaging at MGH before taking up an independent position as Instructor in Radiology at the same institution in 2004. In 2005, she accepted a second academic appointment at UCSD.
The core of Dr Devor’s research program is focused on dissecting neuronal, glial and vascular mechanisms that underlie signals obtained with noninvasive brain imaging modalities such as fMRI. She has published extensively on imaging and recording of brain activity using 2-photon microscopy, voltage- and calcium-sensitive sensors, O2-sensitive phosphorescent probes, intrinsic optical contrasts and extracellular electrophysiological recordings. These microscopic measurements are integrated in a computational framework that allows prediction of macroscopic fMRI responses. Dr Devor also applies novel imaging technologies for in vivo investigation of mouse models of neurological disease and human stem cell-derived neurons transplanted in the mouse brain.
11:45-12:15
The neurovascular unit in health and disease: lessons from animal models
Professor Costantino Iadecola, Weill Cornell Medicine, USA
Abstract
The concept of neurovascular unit (NVU) emerged from the first Stroke Progress Review Group meeting of the National Institutes of Health in the year 2000, to highlight the close developmental, structural and functional interactions between neurons, glia and the cerebral vasculature.The NVU concept emphasised the symbiotic relationship between brain cells and cerebral blood vessels in health and disease. Over the past 18 years, the NVU construct has evolved considerably. In addition to astrocytes, neurons, smooth muscle cells, and endothelium, new cell types have emerged as critical components of the NVU, such as pericytes and perivascular macrophages, etc. The extracellular matrix, matrix proteases and basement membranes (matrisome) constitute an integral part of the NVU. The NVU has also emerged as a guardian of innate and adaptive immune homeostasis and as a key regulator of the trafficking of immune cells in and out of the brain. New trophic interactions have been discovered between vascular cells and brain cells (neurons, astrocytes and oligodendrocytes), which are essential for brain survival and repair. Furthermore, the NVU is involved in the clearance of unwanted molecules from the brain and in proteostasis through the blood–brain barrier (transvascular pathway) or the perivascular space (peri- and para-vascular pathways). These critical functions of the NVU are impaired by vascular risk factors, eg, hypertension, by ageing and by pathological changes associated with Alzheimer’s disease. Consequently the NVU has taken centerstage in a wide variety of brain diseases, but particularly in conditions associated with cognitive impairment. This presentation will provide a brief overview of the structure and function of the NVU and of its critical role in brain function and cognitive health.
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Professor Costantino Iadecola, Weill Cornell Medicine, USA
Professor Costantino Iadecola, Weill Cornell Medicine, USA
Professor Costantino Iadecola is the Director and Chair of the Brain and Mind Research Institute at Weill Cornell Medicine. He has published over 300 journal articles and plays a leadership role in national and international networks for stroke and dementia research. Dr Iadecola is a recipient of two Javits Awards (2009 and 2015) from the National Institutes of Health, the Willis Award from the American Heart Association (AHA), and of the Zenith Fellow Award from the Alzheimer’s Association. In 2015 he received the Excellence Award for Hypertension Research (Novartis-AHA), in recognition of his seminal work on Alzheimer’s disease pathology and hypertension. He is on the editorial boards of several journals and has been active in various editorial capacities for Stroke, Hypertension, Circulation, the Proceedings of the National Academy of Sciences, and the Journal of Neuroscience. In 2015 he was elected to the Association of American Physicians. Dr Iadecola is currently the Principal Investigator of several NIH grants and of grants from the Leon Levy Foundation and the Leducq Foundation.