Wataru Inoue
Assistant Professor
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PH.D. McGill University |
Research interests: My lab uses a multidisciplinary approach including patch clamp electrophysiology, optogenetics, biochemical & histological analysis, and behavioral & physiological manipulations in order to understand the mechanistic underpinning for how stress changes the functioning of the brain, and consequently behaviour. Stress triggers a so-called “fight-or-flight” response. This rapid defense mechanism involves coordinated changes in both psychological (ex. fear, aggression) and physiological (ex. release of stress hormone corticosteroids, elevation of heart rate) functions collectively enhance our ability to handle impending challenges. In addition to this immediate response, stress promotes associative learning that lasts beyond the stressful experience. In other words, we form a memory of a stressful episode and this memory reshapes the way we will respond to future challenges. The major goal of my research is to understand the neurobiological underpinnings by which stress modifies neural functions, and thereby fine-tunes future responses to stress. Specifically, we aim (1) to understand the fundamental cellular and molecular mechanisms through which stressful experiences influence neural and synaptic plasticity in specific stress-related brain circuits, (2) to examine how different modalities, intensities and durations of stress cause different types of neural plasticity, (3) to investigate causal relationships between stress-associative neural plasticity and the changes in physiological functions and behavior. The key questions we ask and techniques we use are: How stress modifies neural circuits? My current research aims at understanding the fundamental mechanisms by which stress causes functional changes in synaptic transmission (synaptic plasticity). To study this, we use patch clamp electrophysiology in brain slices prepared from mice and rats subjected to various stress paradigms. We also combine optogenetics with ex vivo electrophysiology as well as in vivo stress paradigms in order to examine the roles of genetically and anatomically defined neural circuits in stress-associative synaptic plasticity and learning. How does glia contribute to stress-associative neural plasticity and learning? It has become evident that glial cells (eg. astrocytes and microglia) strongly influence synaptic transmission and plasticity via complex neuron-glia interactions. In its simplest form, the release of neurotransmitters (as a result of neural activity) acts on and stimulates nearby glia, which in turn signal back to neurons to modulate synaptic transmission. To understand how glia contribute to stress-associative neural plasticity, we use a combination of techniques including electrophysiological, biochemical (qPCR, ELISA, WB etc.), anatomical (immunohistochemistry and in situ hybridization), pharmacological and genetic approaches. How excessive stress causes maladaptive neural plasticity? Excessive stress, vulnerability to stress, or a combination of both increases the risk for various illnesses including depression, post traumatic stress disorder, hypertension and immune dysfunction. The pathogenesis of such stress-related disorders likely involves forms of neural plasticity that give rise to maladaptive physiological and psychological alterations that in turn make up the symptoms of these diseases. Along with this line of idea, my lab uses chronic stress paradigms (animal models of depression) to identify specific forms of neural plasticity that may underlie the physiological and behavioral symptoms of depression. In particular, my current research focuses on the potential roles of inflammatory processes and glial activation that may be involved in the development of neural plasticity that is characteristic of the chronically stressed brain and depression-related physiological and psychological symptoms. My research may lead to promising drug targets and the development of novel, evidence-based stress-coping strategies. Expertise: Join: The Inoue lab will open July 2014. If you are interested in a graduate position in my lab, please send an email to (winoue@uwo.ca) with a brief description of your scientific interests and career goals. Motivation, enthusiasm and curiosity are required. Previous lab experience will be valued, but is not necessary. All lab members are expected to work hard and efficiently to perform high-level science and enjoy life. Y If you are looking for a post-doc position, please send an email to (winoue@uwo.ca) with a brief description of your past and future projects, and your CV. Individuals who have (solid chance of) a fellowship support will be given high priority.
Synaptic physiology and plasticity
Electrophysiological analysis of synaptic functions
Optogenetic
Stress physiology and regulation of homeostasis (animal experiments quantifying physiological and behavioral parameters)
Immunohistochemistry
Molecular and biochemical techniques (qPCR, ELISA, Western blotting)
Selected Publications: Inoue W, and Bains JS. Beyond inhibition: GABA synapses tune the neuroendocrine stress axis, BioEssays (in press) Inoue W, Baimoukhametova DV, Füzesi T, Wamsteeker Cusulin JI, Koblihger K, Whelan PJ, Pittman QJ, and Bains JS. Noradrenaline is a stress-associated metaplastic signal at GABA synapses., Nature Neuroscience 16(5):605-12 (2013) Wamsteeker Cusulin JI, Füzesi T, Inoue W, and Bains JS. Glucocorticoid feedback uncovers retrograde actions of opioids at GABA synapses, Nature Neuroscience, 16(5):596-604 (2013) Crosby KM*, Inoue W*, Pittman QJ, Bains JS. Endocannabinoids gate state-dependent plasticity of synaptic inhibition in feeding circuits. Neuron 71(3):529-41 (2011) *Contributed equally. Rummel C*, Inoue W*, Poole S and Luheshi GN. Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation. Molecular Psychiatry 15(5):523-34 (2010) *Contributed equally Inoue W, Somay G, Poole S, and Luheshi GN. Immune-to-brain signaling and central prostaglandin E2 synthesis in fasted rats with altered lipopolysaccharide-induced fever. American Journal of Physiology, Regulatory Integrative and Comparative Physiology 295(1):R133-43 (2008) Inoue W, Poole S, Bristow AF, and Luheshi GN. Leptin induces cyclooxygenase-2 via an interaction with interleukin-1beta in the rat brain. European Journal of Neuroscience 24(8):2233-45 (2006)
