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Integrative Neuroscience Laboratory

stress, mental health, autonomic physiology, optogenetics, DREADDs...


Staff (T-B: YoYo Otsuka, Bill Blessing, Mazher Mohammed)

and equipment

 

Research Summary

The Integrative Neuroscience Laboratory uses physiological, neuroanatomical, pharmacological and modern genetic methods to investigate the manner in which the brain controls bodily function in a resting or stressful condition.

Research Projects

When we are under stressful condition in daily life, we often feel emotional changes and physiological stress/emotional reaction such as a rapid heart rate, a pale skin, and an increase in body temperature known as emotional-hyperthermia or psychogenic fever. Our ultimate research goal is to elucidate brain mechanisms that process emotional changes. Emotional changes can be evaluated with verbal communication in human, but not in experimental animals. The physiological emotional reactions are observed in experimental animals such as mice, rats and rabbits. The pale skin is resulted from a decrease in blood flow to skin, and we have established technique to perform simultaneous measurement of skin blood flow, body and brown adipose tissue (BAT, major thermogenic tissue) and brain activity (electroencephalograph) in rats under free-moving condition. In our laboratory, we use resident-intruder stress test to cause emotional-hyperthermia and a pale skin in experimental animals, and measure physiological parameters including BAT temperature to evaluate emotional changes. We are currently investigating brain neural circuit underlying the link between stress and physiological changes, focusing on the orexin system and the serotonergic system. Recently we launched a new project targeting the habenula complex, which is a phylogenetically old brain region of the diencephalon.
Brain orexin and serotonergic systems are closely related to arousal and emotion that are strongly affected by a stressful event. In order to target these systems, we obtained several transgenic rats and mice from Prof Masashi Yanagisawa at the Southwestern Medical Center, University of Texas, and from Prof Akihiro Yamanaka at the Department of Neuroscience II, Nagoya University, Japan. We have setup the first breeding colony these rats and mice in Australia. 
Our research takes modern genetic approach to incorporate optogenetics and pharmacogenetics including DREADDs (designer receptors exclusively activated by designer drugs) in-vivo study.

The daily life of the laboratory rat, with continuous access to food, is organized into alternating periods of activity and inactivity; the basic rest-activity cycle (BRAC). Our laboratory has shown that during active periods (occurring approximately every 90 minutes), body, brain and brown adipose tissue (BAT) temperatures increase. These increases are phase-linked with cardiovascular events. When food is continuously available, eating commences approximately 15min after the onset of an increase in BAT/brain/body temperature, and at virtually no other time. Remarkably, if no food is available and the rat disturbs the empty food container, this action also occurs 15min after the onset of an episodic increase in BAT/brain/body temperature, and at virtually no other time. Thus, food intake is integrated into the BRAC in a precisely timed, highly patterned manner. We are investigating whether or not the physiological changes occurring in the BRAC are modulated by the orexin-synthesizing neurons in the hypothalamus.

Selected Publications

Ootsuka Y, Tanaka M (2015) Control of cutaneous blood flow by central nervous system. Temperature, 2(3):392-405 www.tandfonline.com/doi/full/10.1080/23328940.2015.1069437

 

Otsuka Y and Mohammed M (2015) Activation of the habenula complex evokes autonomic physiological responses similar to those associated with emotional stress. Physiological Reports, 3:e12297

 

Mohammed M, Ootsuka Y, Blessing W (2014) Brown adipose tissue thermogenesis contributes to emotional hyperthermia in a resident rat suddenly confronted with an intruder rat. American Journal of Physiology - Regulatory, integrative and comparative physiology, 306(6):R394-400

 

Mohammed M, Otsuka Y, Yanagisawa M and Blessing W (2014) Reduced brown adipose tissue thermogenesis during environmental interactions in transgenic rats with ataxin-3-mediated ablation of hypothalamic orexin neurons. American Journal of Physiology - Regulatory, integrative and comparative physiology, 307(8):R978-R989

 

Blessing W, Mohammed M, Ootsuka Y (2013) Brown adipose tissue thermogenesis, the basic rest-activity cycle, meal initiation, and bodily homeostasis in rats. Physiology & Behavior, 121:61-69

 

Kontos A, de Menezes RC, Ootsuka Y, Blessing W (2013) Brown adipose tissue thermogenesis precedes food intake in genetically obese Zucker (fa/fa) rats. Physiology & Behavior, 118:129-137

 

Mohammed M, Kulasekara K, De Menezes RC, Ootsuka Y, Blessing WW (2013) Inactivation of neuronal function in the amygdaloid region reduces tail artery blood flow alerting responses in conscious rats. Neuroscience, 228:13-22

 

Kuroki C, Takahashi Y, Ootsuka Y, Kanmura Y, Kuwaki T (2013) The Impact of Hypothermia on Emergence from Isoflurane Anesthesia in Orexin Neuron-Ablated Mice. Anesthesia and Analgesia, 116:1001-1005

 

Yonemitsu T, Kuroki C, Takahashi N, Mori Y, Kanmura Y, Kashiwadani H, Ootsuka Y, and Kuwaki T (2013) TRPA1 detects environmental chemicals and induces avoidance behavior and arousal from sleep. Science Report, 3:3100

 

Blessing W, Mohammed M, Ootsuka Y (2012) Heating and eating: brown adipose tissue thermogenesis precedes food ingestion as part of the ultradian basic rest-activity cycle in rats. Physiology & Behavior, 105(4):966-74

 

Ootsuka Y, Kulasekara K, de Menezes RC, Blessing WW (2011) SR59230A, a beta-3 adrenoceptor antagonist, inhibits ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating. American Journal of Physiology - Regulatory, integrative and comparative physiology, 301(4):R987-994

 

Blessing E, Kader L, Arpandy R, Ootsuka Y, Blessing W, Pantelis C (2011) Atypical antipsychotics cause an acute increase in cutaneous hand blood flow in patients with schizophrenia and schizoaffective disorder. Australian and New Zealand Journal of Psychiatry, 45(8):646-653

 

Blessing WW and Benarroch EE (2011) Lower brainstem regulation of visceral, cardiovascular and respiratory function. Chapter 29 in: The Human Nervous System, 3rd edition (eds G Paxinos and JK Mai) Academic Press, California USA 2011

 

Morrison SF and Blessing WW (2011) Central Nervous Regulation of Body Temperature, Chapter 18 in Central Regulation of Autonomic Function (IJ Llewellyn-Smith and AJM Verberne [ed]) Oxford University Press, New York USA 2011

 

Capuano B, Crosby IT, McRobb FM, Taylor DA, Vom A, Blessing WW (2010) JL13 has clozapine-like actions on thermoregulatory cutaneous blood flow in rats: involvement of serotonin 5-HT1A and 5-HT2A receptor mechanisms. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 34(1):136-42

 


Investigators

  • William Blessing, BA, MBBS, PhD, FRACP

  • Yoichiro (YoYo) Otsuka, BSc, MSc, PhD(Japan) - (Alternative spelling: Youichirou Ootsuka)

  • Mariana Brizuela, PhD

Support Staff

  • Melissa Cox, Laboratory Assistant

    Harman Sharma, Research Assistant

Students

  • Anna Antipov, Honours Student

    Vanshika Sinh, Honours Student

    Kim Luong, MD Advanced Studies Student

    Ang James, MD Advanced Studies Student


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