Biology subjects

Mistlberger, R.

Publications and source records attributed to Mistlberger, R..

3 recordsLinked to original sources

bioRxiv2026

Standard touchscreen test procedures shift circadian rhythms in mice: a modified protocol to minimize circadian confounds

Touchscreen based cognitive testing for rodents offers considerable experimental benefits, including a semi automated battery approach and the use of appetitive rather than aversive reinforcement. However, food reward and touchscreen illumination introduce potential confounds, as both food and light can shift, entrain, or disrupt circadian rhythms, which in turn can affect learning and memory. The potential for the test apparatus to impact endogenous circadian rhythms is particularly problematic when probing relationships between sleep, circadian disruption, and cognitive performance. After observing phase shifting of circadian rhythms in nocturnal mice tested using standard touchscreen test procedures, which include testing during the active period (early lights off), we evaluated the relative contributions of the illuminated screen and the appetitive food reward. Our results indicate that light emitted by the touchscreen chambers is responsible for the circadian phase shifting effects, with standard screen conditions inducing a ~3.5 h phase delay in daily activity rhythms when training is conducted early in the dark period for 7 consecutive days. We then modified lighting in the test environment and the home cage to identify parameters that would minimize circadian shifting without impairing visual discrimination or performance on a widely used cognitive test (Trial Unique Nonmatching to Location, TUNL). From the 10 conditions tested, we offer specific recommendations for modifying touchscreen test protocols to minimize circadian confounds, without impacting task acquisition or performance.

animal behavior and cognition↗

bioRxiv2026

Modelling shiftwork and sleep fragmentation in mice: behavioural phenotypes and implications for hippocampal neurogenesis

Sleep disturbances compromise cognition, and overall physical and mental health; however, animal models of these effects remain limited, and typically impose more extreme disturbances than those experienced by humans. Here, we use behavioural interventions in mice to model two common types of sleep disruption: (1) sleep displacement associated with shiftwork and (2) sleep fragmentation associated with aging and disease. C57BL6/J mice were subjected to either a sleep deprivation protocol (n = 8, females = 4) or a fragmentation protocol (n = 8, females = 4), in which they were completely deprived of sleep or awoken every 2 min respectively, for 12 hours during their typical rest phase (lights-on) across 7 consecutive days. Age-matched control mice (n = 14, females = 7) remained undisturbed in their home cages. Activity during the 12-hour active phase was recorded via infrared motion sensors. After protocol completion, mice were injected with bromodeoxyuridine (BrdU, 200mg/kg) 2 hours prior to brain and blood collection; hippocampal neurogenesis and plasma corticosterone were then assessed. Results show that the sleep deprivation and fragmentation protocols had different, dynamic effects on behaviour; sleep deprivation was associated with an accumulating sleep need, operationalized as progressively reduced locomotor activity across the week, whereas fragmentation produced only an acute reduction of locomotor activity. Cell proliferation rates and corticosterone did not differ from controls. These protocols provide a foundation for future research into the mechanistic links between shiftwork and sleep fragmentation on health and cognition.

neuroscience↗

bioRxiv2020

Mice hypomorphic for Pitx3 define a minimal dopamine neuron population sufficient for entraining behavior and metabolism to scheduled feeding

Pitx3ak mice lack a functioning retina and nearly all dopamine neurons of the substantia nigra (SN). del Rio-Marten et al (2019) reported that entrainment of circadian rhythms to daily light-dark and feeding schedules is absent in these mice. With food limited to 12h/day, food anticipatory circadian rhythms failed to emerge, and metabolic rhythms failed to synchronize with locomotor and feeding rhythms. The authors propose that retinal innervation of the suprachiasmatic nucleus clock is required for development of cyclic metabolic homeostasis, but methodological issues limit interpretation of the results. Using standardized feeding schedules and procedures for distinguishing free-running from entrained circadian rhythms, we confirm that behavioral and metabolic rhythms in Pitx3ak mice do not entrain to LD cycles, but we find no desynchrony between these rhythms nor a deficit in entrainment to daily feeding schedules. SN dopamine neurons surviving in Pitx3ak mice may define a mininum population sufficient for food entrainment.

neuroscience↗