Biology subjects

Piggins, H. D.

Publications and source records attributed to Piggins, H. D..

7 recordsLinked to original sources

bioRxiv2026

Conserved circadian membrane rhythms arise from divergent cellular mechanisms in pacemaker neurons of mice and Drosophila

Circadian clocks align physiology and behaviour with daily environmental cycles, requiring neuronal networks that reliably encode and transmit time-of-day information. A fundamental yet unresolved question is how membrane properties support this function and whether conserved principles arise across evolutionarily distant organisms. We compared the intrinsic electrophysiological properties of identified circadian neurons from a nocturnal mammal (mouse, Mus musculus SCN VIP neurons) and a diurnal insect (fly, Drosophila melanogaster l-LNv PDF neurons) across the 24-h light-dark cycle. Despite [~]700 million years of evolutionary divergence and opposite temporal niches, we found neurons from both species exhibited similar rhythmic patterns in key parameters for encoding time-of-day, including resting membrane potential, spontaneous firing rate and cell capacitance, indicating convergent strategies for generating daily variation in excitability despite dramatically different network scales ([~]2200 VIPs vs. 8 l-LNvs). These shared outputs arose through distinct mechanisms: flies exhibited higher input resistance, greater excitability and relatively larger A-type potassium currents, while mice displayed larger sustained outward currents and post-inhibitory rebound excitation, absent in flies. Rheobase troughs occurred during the inactive phase in both species, while other parameters did not cycle. These differences likely shape how each neuronal type integrates salient inputs, consistent with their respective roles in processing sustained daytime light (flies) versus nocturnal cues (mice). Our findings reveal conserved functional goals but divergent electrophysiological strategies in circadian neurons, reflecting evolutionary adaptation to species-specific environmental demands. Such neurophysiological diversity highlights how evolution shapes cellular mechanisms to meet the requirements of temporal niche while preserving robust circadian timekeeping.

neuroscience↗

bioRxiv2026

Beyond the Barrier: An Assessment of Social Behaviour in Mice using a Modified 3-Chamber Test

BackgroundThe three-chamber test (3CT) is widely used to assess social behaviour in mice, based on the assumption that time spent near a conspecific reflects motivation for social contact. However, the design of the task constrains interpretation, as behaviour may reflect exploration, novelty seeking, or territorial investigation rather than affiliative social motivation. In addition, key biological factors such as sex differences and social hierarchy are often overlooked. AimsWe hypothesised that the 3CT overestimates sociability and used a direct-interaction phase to investigate motivation for affiliative social contact. We also integrated social status to determine if this modulated behavioural patterns and interacted with sex. MethodsAdult male and female C57BL/6 mice (n = 32) were tested in a standard 3CT, followed by removal of the cage barrier to permit direct contact. Behavioural parameters were quantified, and social status was determined using the tube test. ResultsMales exhibited higher social interest index scores than females. Once the barrier was removed, both sexes displayed a negative direct sociability index, indicating greater environmental exploration than social engagement. Correlation analysis revealed no association between indirect and direct measures. Sex differences emerged primarily among submissive mice, with submissive males showing greater social investigation than submissive females. ConclusionThese findings suggest that standard 3CT indices reflect exploratory rather than affiliative social motivation. The modified paradigm incorporating direct interaction provides a more realistic assessment of social behaviour and challenges assumptions about intrinsic sociability in mice.

neuroscience↗

bioRxiv2025

Differential Effects of Sex and Age on Daily and Infradian Rhythms of Mice Running Title: Sex and Age Differences in Mouse Rhythms

Intrinsic biological rhythms regulate key physiological and behavioural processes, yet the influence of sex and age on these rhythms is not fully understood. We comprehensively examined 24-hour (circadian) and >24-hour (infradian; 5-day and 10-day) rhythms in wheel-running and ingestive behaviours in single-housed young and middle-aged male and female mice. Circadian analysis revealed that middle-aged mice, particularly females, exhibited more precise daily rhythms and shifted a greater proportion of activity and feeding to the lights-on phase compared to young female mice. Middle-aged animals also ran for longer durations per day, suggesting age-related changes in activity regulation. Analysis of infradian rhythms further highlighted sex- and age-specific differences. Young female mice displayed robust 5-day rhythms in wheel-running activity, which were absent in middle-aged females. In contrast, few males (young or middle-aged) showed significant 5-day rhythms. Ten-day rhythms were most prominent in male mice, while females rarely expressed this periodicity. Physiologically, middle-aged mice lost more body weight in response to single housing, with middle-aged females being most affected. Interactions among behavioural rhythms in females also showed greater complexity, which increased with age. These findings reveal distinct sex- and age-dependent patterns in circadian and infradian rhythms as well as in physiological responses to isolation. Our work highlights the need to account for sex and age in chronobiological research, with broader implications for understanding vulnerability to age-related metabolic and behavioural disorders.

animal behavior and cognition↗

bioRxiv2024

Food-entrainment of circadian timekeeping in the dorsal vagal complex

The dorsal vagal complex (DVC) is a multi-component brainstem satiety centre which has gained attention as a key target of anti-obesity pharmacotherapies. Our recent studies revealed its circadian timekeeping properties, with molecular and electrophysiological 24h rhythms persisting independently of the primary hypothalamic clock. However, the factors entraining these brainstem oscillators, and the downstream transcriptional targets of the DVC molecular clock remain unclear. Here, using fluorescent in situ hybridisation, we demonstrate core clock gene expression in inhibitory and excitatory neuronal populations of the DVC, as well as in its output cholinergic vagal neurons. We further reveal that the molecular clock is associated with rhythmic expression of numerous neurotransmitter receptor genes in the DVC in vivo, with the phase of both clock and clock-controlled gene expression tightly regulated by meal timing. These findings uncover food-entrained circadian rhythms in the DVC and have important implications for clinical studies targeting brainstem satiety mechanisms.

neuroscience↗

bioRxiv2021

Rhythmic neuronal activities of the rat nucleus of the solitary tract are impaired by short-term high fat diet - implications for daily control of satiety by the brainstem

Temporal partitioning of daily food intake is crucial for survival and involves the integration of internal circadian states and external influences such as the light-dark cycle and the composition of diet. These intrinsic and extrinsic factors are interdependent with misalignment of circadian rhythms promoting body weight gain, while consumption of a calorie dense diet elevates the risk of obesity and blunts circadian rhythms. Since cardiovascular disease, metabolic disorders, and cancer are comorbid with obesity, understanding the relationships between brain activity and diet is of pivotal importance. Recently, we defined for the first time the circadian properties of the dorsal vagal complex of the brainstem, a structure implicated in the control of food intake and autonomic tone, but if and how 24 h rhythms in this area are influenced by diet remains unresolved. Here we focused on a key structure of this complex, the nucleus of the solitary tract, and using a range of approaches, we interrogated how its neuronal and cellular rhythms are affected by high-fat diet. We report that short term consumption of this diet increases food intake during the day and blunts daily rhythms in gene expression and neuronal discharge in the nucleus of the solitary tract. These alterations in this structure occur without prominent body weight gain, suggesting that high-fat diet acts initially to reduce activity in the nucleus of the solitary tract, thereby disinhibiting mechanisms that suppress daytime feeding. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/433567v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@243b7borg.highwire.dtl.DTLVardef@bd3886org.highwire.dtl.DTLVardef@c9f427org.highwire.dtl.DTLVardef@bc52cd_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Daily changes in neuronal activities of the dorsal motor nucleus of the vagus under standard and short-term high fat diet - implications for circadian modulation of parasympathetic outflow

The suprachiasmatic nuclei (SCN) of the hypothalamus functions as the brains primary circadian clock, but circadian clock genes are also rhythmically expressed in several extra-SCN brain sites where they can exert local temporal control over physiology and behaviour. Recently, we found that the hindbrain dorsal vagal complex possesses strong daily timekeeping capabilities, with the area postrema and nucleus of the solitary tract exhibiting the most robust clock properties. The possibility that the executory part of this complex - the dorsal motor nucleus of the vagus (DMV), also exhibits daily changes has not been extensively studied. The DMV is the source of vagal efferent motoneurons largely responsible for the regulation of gastric motility and emptying and consequently influence meal size and energy homeostasis. We used a combination of multi-channel electrophysiology and patch clamp recordings to gain insight into possible daily variation in these DMV cells and how this is influenced by diet. We found that DMV neurons increase their spontaneous activity, excitability and responsiveness to metabolic neuromodulators at late day which was paralleled with an enhanced synaptic input to these neurons. A high-fat diet typically damps circadian rhythms, but we found that short-term exposure to a high-fat diet paradoxically amplified daily variation of DMV neuronal activity, while blunting their responsiveness to metabolic neuromodulators. In summary, we show for the first time that neural activity at a source of vagal efferents varies with time of day and that this temporal variation is modulated by diet. These findings have clear implications for our understanding of the daily control of parasympathetic outflow.

neuroscience↗

bioRxiv2019

Circadian control of intrinsic heart rate via a sinus node clock and the pacemaker channel

In the human, there is a circadian rhythm in the resting heart rate and it is higher during the day in preparation for physical activity. Conversely, slow heart rhythms (bradyarrhythmias) occur primarily at night. Although the lower heart rate at night is widely assumed to be neural in origin (the result of high vagal tone), the objective of the study was to test whether there is an intrinsic change in heart rate driven by a local circadian clock. In the mouse, there was a circadian rhythm in the heart rate in vivo in the conscious telemetrized animal, but there was also a circadian rhythm in the intrinsic heart rate in denervated preparations: the Langendorff-perfused heart and isolated sinus node. In the sinus node, experiments (qPCR and bioluminescence recordings in mice with a Per1 luciferase reporter) revealed functioning canonical clock genes, e.g. Bmal1 and Per1. We identified a circadian rhythm in the expression of key ion channels, notably the pacemaker channel Hcn4 (mRNA and protein) and the corresponding ionic current (funny current, measured by whole cell patch clamp in isolated sinus node cells). Block of funny current in the isolated sinus node abolished the circadian rhythm in the intrinsic heart rate. Incapacitating the local clock (by cardiac-specific knockout of Bmal1) abolished the normal circadian rhythm of Hcn4, funny current and the intrinsic heart rate. Chromatin immunoprecipitation demonstrated that Hcn4 is a transcriptional target of BMAL1 establishing a pathway by which the local clock can regulate heart rate. In conclusion, there is a circadian rhythm in the intrinsic heart rate as a result of a local circadian clock in the sinus node that drives rhythmic expression of Hcn4. The data reveal a novel regulator of heart rate and mechanistic insight into the occurrence of bradyarrhythmias at night.

physiology↗