PRISM: Physiological Regulation in Sleeping Mice - University of Bologna

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.