Header image 1Header image 2Header image 3Header image 4Header image 5

Integrative Neuroscience Laboratory

thermoregulation, viral vectors, optogenetics, chemogenetics...


Lab Members left to right: Bill Blessing, Mariana Brizuela,
Melissa Cox, Yoichiro Otsuka, Anna Antipov, Vanshika Sinh

 

 

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.

 

 

EEG Fourier-power (the top trace), body temperature (the second trace), heart rate (the third trace), food (the fourth trace), and locomotor activity (the fifth trace) records in a WT mouse under un-anaesthetised and unrestrained condition. Continuous wavelet-power spectrum of EEG Fourier-power were shown above the EEG power trace. The colour changes as power increases of frequency components from blue to white. The significant wavelet-power areas were indicated by the pink contours. A broken line was place at the onset of each eating. The black and white bars at the bottom indicate light off (12 hours) and light on (12 hours), respectively. (Temperature, 1-11, (2016)).

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, 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 humans, 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 several techniques to perform simultaneous measurement of skin blood flow, body and brown adipose tissue (BAT, major thermogenic tissue) temperature, and brain activity (electroencephalograph) in rats under free-moving condition. In our laboratory, we use resident-intruder stress test to cause emotional-hyperthermia and pale skin in experimental animals, and measure physiological parameters including BAT temperature to evaluate emotional changes. We are currently investigating brain neural circuits underlying the link between stress and physiological changes, focusing on the habenula complex, which is a phylogenetically old brain region of the diencephalon. Since the habenula complex sends neural projection to midbrain monoaminergic nuclei including the ventral tegmental area (dopaminergic neurons) and the dorsal and median raphe (serotonergic neurons).
The midbrain monoamine systems are closely related to arousal and emotions that are strongly affected by a stressful event. In order to target these systems, we obtained several transgenic mice from Prof Akihiro Yamanaka at the Department of Neuroscience II, Nagoya University, Japan. We have setup the first breeding colony of these mice in Australia. Our research takes a 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

Blessing W & Ootsuka Y (2016) Timing of activities of daily life is jaggy: How episodic ultradian changes in body and brain temperature are integrated into this process. Temperature, 3(3):371-383

 

Miyata K, Kuwaki T & Ootsuka Y (2016) The integrated ultradian organization of behavior and physiology in mice and the contribution of orexin to the ultradian patterning. Neuroscience, 334:119-133

 

Mohammed M, Kulasekara K, Ootsuka Y & Blessing WW (2016) Locus coeruleus noradrenergic innervation of the amygdala facilitates alerting-induced constriction of the rat tail artery. Am J Physiol Regul Integr Comp Physiol, 310:R1109-1119

 

Mohammed M, Yanagisawa M, Blessing W & Ootsuka Y (2016) Attenuated cold defense responses in orexin neuron-ablated rats. Temperature, 3(3):465-475

 

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

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

    William Blessing, BA, MBBS, PhD, FRACP

    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


CNS page footer image
Website by Journeyman Systems