A Snapshot seminar hosted by the School of Physiology, Pharmacology and Neuroscience
Cherrie Kong: Control of Ca2+ release synchrony in cardiac ventricular myocytes
Abstract: Cardiac excitation-contraction coupling (ECC) depends on Ca2+ release from intracellular stores via ryanodine receptors (RyRs) triggered by L-type Ca2+ channels (LCCs). Uncertain numbers of RyRs and LCCs form ‘couplons’ whose activation produces Ca2+ sparks, which summate to form the Ca2+ transient. Voltage changes during the action potential (AP) and stochasticity in channel gating should introduce variability in Ca2+ spark timing, however Ca2+ transient wavefronts are remarkably uniform. To investigate these uncertainties, we measured the voltage-dependence of Ca2+ spark activation and developed a detailed computer model to interpret these data. Our analysis provides the first functional estimate of RyR:LCC stoichiometry and coupling efficiency during an AP, as well as an explanation of how Ca2+ release synchrony is achieved.
Daniela Franchini: Deep cerebellar nuclei and food prediction
Abstract: Food consumption is fundamental for life and its regulation depends on multiple interacting factors, including energy homeostasis, emotional factors, and environmental cues such as food availability and time of day. Restricting food availability to a specific time of day (time-restricted feeding) triggers a shift in circadian oscillators in many peripheral organs and brain regions. This is accompanied by the emergence of a daily rhythm of food anticipatory activity (FAA) which manifests as a pre-meal increase in arousal, locomotor activity and body temperature. Evidence has shown that the cerebellum expresses circadian clock genes that are sensitive to feeding cues and that cerebellar ablation leads to a marked reduction in FAA. The cerebellum has, indeed, been shown to be involved in many aspects of feeding, including motor control and appetite regulation. For instance, a recent paper showed that acute activation of mouse deep cerebellar nuclei (DCN) leads to a decrease in food intake. While this evidence points to a potentially very important role of the cerebellum in meal prediction and modulation of appetite, further work is required to understand the physiological mechanisms underlying this process. We performed preliminary experiments on freely-moving mice subject to time-restricted feeding and collected locomotor and neuronal activity under different metabolic states (fed and fasted). Monitoring of locomotor activity during consecutive days showed that our mice developed FAA within a week of scheduled feeding. Simultaneous recordings of calcium activity in the DCN revealed changes in calcium activity at food presentation during the course of this study.