Wataru Inoue

Peter Stathopulos

Assistant Professor

BSc Kyoto University  
MSc Kyoto University 
PhD McGill University, Neurology and Neuroscience 
Post-Doctoral Fellowship University of Calgary

Office:  Robarts Research Institute, Room 7241 
p. 519.931.5777 x. 24373
e. winoue@robarts.ca

Lab: Robarts Research Institute, Room 7233

Twitter: @NeuroStress_Lab

Why Science?
I initially started my undergraduate degree with the intention of becoming an anthropologist simply because I thought I could travel a lot and learn more about the world, but then during fourth year, I participated in a neuroscience lab as part of a rotation and realized the joys of doing experiments. I relished in the fact that I received the same stimulation from finding new knowledge as I did from travelling to new places. I also realized that everything I experienced revolved around how my brain perceived it, which initiated my desire to understand how the brain works. After that, I instinctively knew I wanted to pursue science at a professional level, which led me to do a Masters in neuroscience, which is when I embraced the fact that science is international and began looking for more learning opportunities around the world. This ultimately led me to McGIll University, where I studied brain driven behaviour for sickness and then a Post-Doc investigating how the brain interprets and intercepts stress. The brain is at the core of our behaviour, and in particular I was amazed at how basic bodily changes such as sickness and hunger could powerfully change our motivation and cognitive functions as well as homeostatic function.

Research Goals
The goal of my research is to understand the effects of stress on the functioning of the brain, and consequently behaviour. My lab uses a multidisciplinary approach including patch clamp electrophysiology, optogenetics, biochemical & histological analysis, and behavioral & physiological manipulations in order to understand molecular mechanisms of stress.

Stress causes an immediate physiological and psychological response and promotes associative learning that makes a lasting changes in future behavior; however, the accumulations of memories of stressful episodes can cause many negative consequences. I focus my work on the hypothalamus, which is the part of the brain that regulates hormonal response to stress. Stress-induced changes in this area may represent a key neurobiological mechanism for the abnormality of stress hormone levels and the changes in behaviour, seen in many serious diseases. Thus, I aim to understand the fundamental cellular and molecular mechanisms through which stressful experiences influence neural and synaptic plasticity in specific stress-related brain circuits, examine how different modalities, intensities and durations of stress cause different types of neural plasticity, and investigate causal relationships between stress-associative neural plasticity and the changes in physiological functions and behavior.

Specific Research Interests
1.  How Stress Modifies Neural Circuits
My research aims to understand how the brain changes from various experiences of stress and how various sources of stress cause our brains to react in different ways. I investigate the fundamental mechanisms by which stress causes functional changes in synaptic transmission (synaptic plasticity). A combination of optogenetics, ex vivo and in vivo electrophysiology, and in vivo stress paradigms are utilized to examine the roles of genetically and anatomically defined neural circuits in stress-associative synaptic plasticity and learning. This research can expand our understanding of mental health and how the way we remember a stressor changes our stress response in future occurrences.

2.  How Glia Contribute to Stress-Associative Neural Plasticity and Learning
Glial cells such as astrocytes and microglia strongly influence synaptic transmission and plasticity via complex neuron-glia interactions and play important roles in coordinating neuroplasticity. In its simplest form, the release of neurotransmitters 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.

3.  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. 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 relevant to 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.

Most Rewarding Moments
As a scientist, I experience so much joy when I figure something out for the first time, which can lead to a better understanding of a key mechanism in the body, which then expands our scientific knowledge and can lead to better tools for diagnosis and treatment of disease. Often times, I’ll also stumble upon something unexpected that wasn’t being investigated, which is exciting and adds to the thrill of doing research. There’s so much to discover, and so I also find it really gratifying to see students become interested in research and grow in their respective fields.

Awards and Recognitions
2013 David Proud Award for Research Excellence, University of Calgary
2013 Hotchkiss Brain Institute, Postdoctoral Researcher of the Year, University of Calgary

Publications
See my publications on Pubmed.

See my publications on Google Scholar.

Highlighted Publications
Sunstrum J, Inoue W. Heterosynaptic modulation in the paraventricular nucleus of the hypothalamus. Neuropharmacology, doi.org/10.1016/j.neuropharm.2018.11.004 (2018). Link to article.

Khazaeipool Z, Weiderman M, Inoue W. Prostaglandin E2 depresses GABA release onto parvocellular neuroendocrine neurones in the paraventricular nucleus of the hypothalamus via presynaptic receptors. Journal of Neuroendocrinology  Nov;30(11):e12638 (2018). Link to article.

Salter E, Sunstrum J, Matovic S, Inoue W. Chronic stress dampens excitatory synaptic gain in the paraventricular nucleus of the hypothalamus. Journal of Physiology pp 4157-4172, DOI: 10.1113/JP275669 (2018). Link to article.

Bains JS, Wamsteeker Cusulin JI, and Inoue W. Stress-related synaptic plasticity in the hypothalamus. Nature Reviews Neuroscience 16(7):377-88 (2015). Link to article.

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). Link to article.