Division of BioMedical Sciences
Faculty of Medicine
Memorial University of  Newfoundland
300 Prince Phillip Drive
St. John's, NF,  Canada  A1B 3V6
t;709-777-6727

michiru@mun.ca

Research Interest:

Neuronal mechanisms of appetite and alertness Healthy eating and good night sleep are important facets of being healthy and happy in everyday life. In modern society, however, many people struggle to fight against temptations of palatable food loaded with fat, sugar and salt, and as a result the obesity rate continues to rise. Inadequate sleep has also become increasingly common. In fact, a relationship between obesity and sleep disorders has been suggested. Orexin neurons and related neural circuits may directly link appetite and sleep-wake cycle. These neurons are responsible for increasing appetite and vigilance in a coordinated manner, which is necessary for searching and consuming food as well as for the active brain to have enough supply of energy substrate. We are interested in understanding how these neurons work, how they are regulated and what changes take place when challenged with high fat diet (appetite stimulation) or infection (appetite inhibition and sleepiness). Our current projects are aimed to determine the regulatory mechanisms of orexin neurons, specifically involving: Reward-related neurotransmitters: Food intake is a motivated behavior that involves the same brain circuitry as addiction, which includes orexin neurons. We are investigating how this circuitry works. High fat diet: Why do we eat too much fatty food? We are testing the hypothesis that high fat diet alters the function of appetite neurons, such as orexin neurons, to override satiety. Energy substrates: How does the brain know it has enough energy supply, and how does it correct it if it is not sufficient? We have found that orexin neurons are sensors of energy substrate lactate, and are responsible for matching energy supply and brain activation. Fever: Our study suggests that the same neurons that induce overeating are responsible for loss of appetite and sleepiness during infection. We are investigating the mechanism underlying sickness behavior.  Effects of sleep deprivation on brain function Lack of sleep results in various physiological and psychological impairments as well as physiological responses necessary for restoring sleep homeostasis. The basal forebrain contains neurons responsible for attention, learning and memory, which play a critical role in sleep recovery after sleep deprivation. In collaboration with Dr. Kazue Semba, Dalhousie University, we are investigating the cellular mechanisms underlying functional and structural changes in basal forebrain neurons induced by sleep deprivation.     Spontaneous neurotransmitter release Synaptic transmission is one of the most fundamental processes in the nervous system and can occur in two modes: precisely timed synchronous transmitter release triggered by action potentials (evoked release) and asynchronous, spontaneous quantal transmitter release independent of action potentials (spontaneous release). Spontaneous release occurs at virtually every synapse, therefore understanding how it occurs and is regulated is critical in order to fully understand how the nervous system works. Using homeostatic neurons as a model, where persistent synaptic activity may be more crucial than precise timing, we are investigating the regulatory mechanisms of spontaneous release.

Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council of Canada
Dr. A. R. Cox Research Grant

People:

Christian O. Alberto
Susan Banfield
Amanda Cranford
Farah Hamodat
Sandeep Muram
Katrin Zipperlin

Recent Publications:

1. C. O. Alberto, R. B. Trask and M. Hirasawa (2011) Dopamine acts as a partial agonist for a2A adrenoceptor in MCH neurons. J. Neurosci. In press
2. J. Burt, C. O. Alberto, M. P. Parsons and M. Hirasawa. Local network regulation of orexin neurons in the lateral hypothalamus. Am. J. Physiol. In press
3. M. P. Parsons and M. HIrasawa (2011) GIRK channel-mediated inhibition of melanin-concentrating hormone neurons by nociceptin/orphanin FQ. J Neurophysiol. 105(3):1179-84.
4. M. P. Parsons and M. Hirasawa (2010) ATP-sensitive potassium channel- mediated lactate effect on orexin neurons: implications for brain energetics during arousal. J. Neurosci. 30(24):8061-70.
5. C.O. Alberto and M. Hirasawa (2010) AMPA receptor-mediated miniature EPSCs have heterogeneous time courses in orexin neurons. Biochem Biophys Res Commun 400(4): 707-712.
6. M.E. Quinlan, C. O. Alberto and M. Hirasawa (2008). Short-term potentiation of mEPSCs requires N-, P/Q- and L-type Ca++ channels and mitochondria in the supraoptic nucleus. J. Physiol. 586(13): 3147–3161.
7. M. Hirasawa, X. Xu, R. B. Trask, T. P. Maddatu, B. A. Johnson, S. L. Ackerman, J. K. Naggert, P. M. Nishina, and A. Ikeda (2007). Car8 mutation results in aberrant synaptic morphology and impaired excitatory synaptic function in the cerebellum. Mol. Cell. Neurosci. 35(1):161-70.
8. M. Hirasawa, M. P. Parsons and C. O. Alberto (2007). Interaction between orexins and the mesolimbic system for overriding satiety. Rev. Neurosci.18, 383-393.
9. C.O. Alberto, R. B. Trask, M. E. Quinlan and M. Hirasawa (2006). Bidirectional dopaminergic modulation of excitatory synaptic transmission in orexin neurons. J. Neurosci. 26(39):10043-50.