Biology subjects

van der Vinne, V.

Publications and source records attributed to van der Vinne, V..

3 recordsLinked to original sources

bioRxiv2022

EPHierStats: a statistical tool to model the hierarchical relationships in electrophysiological data

Electrophysiological datasets are typically analyzed under the assumption that repeated measurements of the same unit of analysis (i.e. neuron or animal) can be treated as statistically independent. Recently, this assumption has been questioned and our data confirms and quantifies this skepticism using ex vivo slice recordings of synaptic currents in D1R+ medium spiny neurons in the nucleus accumbens. We therefore present EPHierStats as a statistical framework to analyze electrophysiological datasets with large numbers of measurements (>100) per unit of analysis. This novel analysis framework enables encoding of the full hierarchical relationships between measurements in a mixed-effects general linear model while also analyzing the distribution of values in assessed variables. Our method can easily be adapted to analyze a wide range of repeated-measures electrophysiological experiments. Implementation of the EPHierStats tool will aid the adaption of modern statistical approaches that prevent pseudoreplication and its associated false discovery rate while enabling statistical assessments of the complex relationships inherent to the field of neuroscience.

neuroscience↗

bioRxiv2021

Cell-type specific circadian bioluminescence rhythms recorded from Dbp reporter mice reveal circadian oscillator misalignment

Circadian rhythms are endogenously generated physiological and molecular rhythms with a cycle length of about 24 h. Bioluminescent reporters have been exceptionally useful for studying circadian rhythms in numerous species. Here, we report development of a reporter mouse generated by modification of a widely expressed and highly rhythmic gene encoding D-site albumin promoter binding protein (Dbp). In this line of mice, firefly luciferase is expressed from the Dbp locus in a Cre-recombinase-dependent manner, allowing assessment of bioluminescence rhythms in specific cellular populations. A mouse line in which luciferase expression was Cre-independent was also generated. The Dbp reporter alleles do not alter Dbp gene expression rhythms in liver or circadian locomotor activity rhythms. In vivo and ex vivo studies show the utility of the reporter alleles for monitoring rhythmicity. Our studies reveal cell-type specific characteristics of rhythms among neuronal populations within the suprachiasmatic nuclei ex vivo. In vivo studies show Dbp-driven bioluminescence rhythms in the liver of Albumin-Cre;DbpKI/+ "liver reporter" mice. After a shift of the lighting schedule, locomotor activity achieved the proper phase relationship with the new lighting cycle more rapidly than hepatic bioluminescence did. As previously shown, restricting food access to the daytime altered the phase of hepatic rhythmicity. Our model allowed assessment of the rate of recovery from misalignment once animals were provided with food ad libitum. These studies confirm the previously demonstrated circadian misalignment following environmental perturbations and reveal the utility of this model for minimally invasive, longitudinal monitoring of rhythmicity from specific mouse tissues.

physiology↗

bioRxiv2020

Methods for detecting PER2::LUCIFERASE bioluminescence rhythms in freely moving mice

Circadian rhythms are driven by daily oscillations of gene expression. An important tool for studying cellular and tissue rhythms is the use of a gene reporter, such as bioluminescence from the reporter gene luciferase controlled by a rhythmically expressed gene of interest. Here we describe methods that allow measurement of bioluminescence from a freely-moving mouse housed in a standard cage. Using a LumiCycle In Vivo (Actimetrics), we determined conditions that allow detection of circadian rhythms of bioluminescence from the PER2 reporter, PER2::LUC, in freely behaving mice. We tested delivery of D-luciferin via a subcutaneous minipump and in the drinking water. Further, we demonstrate that a synthetic luciferase substrate, CycLuc1, can support circadian rhythms of bioluminescence, even when delivered at a lower concentration than D-luciferin. We share our analysis scripts and suggestions for further improvements in this method. This approach will be straightforward to apply to mice with tissue-specific reporters, allowing insights into responses of specific peripheral clocks to perturbations such as environmental or pharmacological manipulations.

systems biology↗