PRISM: Physiological Regulation in Sleeping Mice, University of Bologna

Department of Biomedical and Neuromotor Sciences - Physiology

Contact:
Giovanna Zoccoli
Position:
Associate Professor
Address:
Piazza di Porta S. Donato, 2, 40126
City:
Bologna
Country:
Italy
Phone:
+39 051 2091726
Fax:
+39 051 2091737
Research Domain
  • Basic Animal
Keywords
  • Molecular Biology-Endocrinology-Biochemistry
  • Genetics of Sleep
  • Sleep and Body Functions (Cardio-Respiratory, Thermoregulation/Metabolism, Endocrine)
  • Sleep Physiology-Neurophysiology in Animal
  • Biological Rhythms

Laboratory description

Any given change in genetic information typically entails an array of differences in interacting physiologic functions, much as a beam of light may be dispersed in its component colours, Physiologic functions such as cardiovascular and respiratory control differ widely between wake-sleep behaviours. Mice are the mammalian species of choice for studies on functional genomics.

The PRISM lab investigates cardiorespiratory phenotype as a function of the wake-sleep behaviour in mice harbouring changes in genetic information, with a focus on genetically-engineered mouse models of human diseases. The main goal of this research is to help unravel the central neural and genetic mechanisms that underlie the physiologic and pathologic effects of sleep on cardiorespiratory control.

Research activity at the PRISM lab is presently focused on the study of hypothalamic integrative activity during sleep. The hypothalamus is a key region in the control of diverse physiologic functions, such as thermoregulation, osmoregulation, metabolism, and autonomic cardiovascular control. The hypothalamic networks underlying these functions are tightly entangled and share common substrates with the regulation of wake-sleep states. Mouse strains with genetic impairments of specific signalling molecules are a powerful tool to understand the role of specific neurotransmitters, neuromodulators, and neural pathways in integrative hypothalamic function during sleep.

The key technical asset of the PRISM lab is to perform simultaneous long-term recordings of multiple physiologic signals in freely-behaving mice. Blood pressure and heart rate are measured by telemetry, which is the technique at the state of the art in conscious mice. These measurements are synchronized with electroencephalographic and electromyographic (postural muscle tone) signals acquired with conventional cable transmission. Respiratory activity is monitored non-invasively with the technique of whole-body plethysmography, which is coupled to measurement of diaphragm electromyography to discriminate central from obstructive apnoeas. Stereotaxic implantation of intracerebral microcannulas allows selective pharmacological manipulation of hypothalamic circuitry. The PRISM lab is also equipped for development and maintenance of mouse colonies. Mouse genotyping with qualitative PCR, gene expression analysis with real-time quantitative PCR, and immunoenzymatic/immunofluorescent assays on plasma and tissue samples are performed with state-of-the-art molecular biology equipment in collaboration with the Centre for Applied Biomedical Research – CRBA at the Bologna University Hospital. Finally, researchers at the PRISM lab are actively involved in translating mathematic tools for analysis and modelling of biosignals developed in the lab to the clinical setting by means of collaborative studies on human subjects.


Additional Descriptors, Keywords

Cardiorespiratory regulation and sleep
Central autonomic control during sleep
Functional genomics


Key Publications of the Laboratory:
Zoccoli G., Walker A.M., Lenzi P., Franzini C. The Cerebral Circulation during Sleep: regulation mechanisms and functional implications. Sleep Med. Rev., 6: 443-455, 2002.

Franzini C. Cardiovascular Physiology: The Peripheral Circulation. In: Principles and Practice of Sleep Medicine. M.H. Kryger, T. Roth, W.C. Dement. (Eds), 4th Ed., Elsevier, Philadelphia, 2005, pp 203 - 212.

Silvani A, Lenzi P. Reflex Cardiovascular Control in Sleep. In: The Physiologic Nature of Sleep. Parmeggiani P.L., Velluti R.A. (Eds), Imperial College Press, London, 2005, pp. 351-369.

Zoccoli G., Bojic T., Franzini C. Regulation of Cerebral Circulation during Sleep. In: The Physiologic Nature of Sleep. Parmeggiani P.L., Velluti R.A. (Eds), Imperial College Press, London, 2005, pp. 351-369.

Silvani A. Physiological sleep-dependent changes in arterial blood pressure: central autonomic commands and baroreflex control (Invited Brief Review). Clin Exp Pharmacol Physiol, 35: 987-94, 2008.

Franzini C. Sleep and Blood Flow. In: Atlas of Clinical Sleep Medicine, M.H Kryger (Ed), Saunders Elsevier, Philadelphia, 2010, pp 49-53.

Zoccoli G., Walker A.M. The Circulation in Sleep in Early Life; critical phases in its functional development and neural control. In: Vegetative Functions and Their Interactions in the Neonate. Chardon K (Ed), Research Signpost, Trivandrum, Kerala, India, 2010, pp 141-159.

Plazzi G., Moghadam K.K., Maggi L.S., Donadio V., Vetrugno R., Liguori R., Zoccoli G., Poli F., Pizza F., Pagotto U., Ferri R. Autonomic disturbances in narcolepsy, Sleep Med. Rev, 15: 187-196, 2011.

Zoccoli G, Amici R, Silvani A. The hypothalamus and its functions. In: Narcolepsy. Pathophysiology, Diagnosis, and Treatment. Baumann CR, Bassetti CL and Scammell TE (eds). Springer, 1st Edition, 2011, pp 191-204.

Zoccoli G., Silvani A. and Franzini C. (2013) Sleep and the Peripheral Vascular System. In: Kushida C.A. (ed.) The Encyclopedia of Sleep, Vol. 1, pp. 563-567. Waltham, MA: Academic Press.

Silvani A, Dampney RAL. Central control of cardiovascular function during sleep (Invited Review). Am. J. Physiol. Heart Circ. Physiol., accepted.

Grimaldi D, Silvani A, Benarroch E, Cortelli P. Orexin/hypocretin system and autonomic control: new insights and clinical correlations (Invited Review) Neurology, accepted.

Collaborations

Title:  PhD

Name:  Rosemary Horne

Position:  Associate Professor

Institution:  Monash University, Melbourne

Title:  PhD

Name:  Gary Cohen

Institution:  Karolinska Institute, Stockholm

Title:  PhD MD

Name:  Hiroshi Ohtsu

Position:  Professor

Institution:  Tohoku University, Sendai, Japan

Title:  PhD MD

Name:  Jian-Sheng Lin

Position:  Professor

Institution:  Université Claude Bernard, Lyon, France

Title:  PhD

Name:  Roger AL Dampney

Position:  Professor

Institution:  University of Sidney

Title:  MD

Name:  Pietro Cortelli

Position:  Associate Professor

Institution:  Univerity of Bologna

Name:  Uberto Pagotto

Position:  Assistant Professor

Institution:  University of Bologna

Name:  Mauro Ursino

Position:  Professor

Institution:  University of Bologna

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