Locomotor Activity Rhythms Research Articles

Exposure to Spectracide® causes behavioral deficits in Drosophila melanogaster: Insights from locomotor analysis and molecular modeling

This study was focused on gaining insights into the mechanism by which the herbicide- Spectracide®, induces oxidative stress and alters behavior in Drosophila melanogaster. Exposure to Spectracide® (50%) significantly (p < 0.05) reduced the negative geotaxis response, jumping behavior and dampened locomotor activity rhythm in adult flies compared to non-exposed flies. Protein carbonyl levels indicative of oxidative damage increased significantly coupled with down-regulation of Sniffer gene expression encoding carbonyl reductase (CR) and its activity in Spectracide®-exposed flies. In silico modeling analysis revealed that the active ingredients of Spectracide® (atrazine, diquat dibromide, fluazifop-p-butyl, and dicamba) have significant binding affinity to the active site of CR enzyme, with atrazine having comparatively greater affinity. Our results suggest a mechanism by which ingredients in Spectracide® induce oxidative damage by competitive binding to the active site of a protective enzyme and impair its ability to prevent damage to proteins thereby leading to deficits in locomotor behavior in Drosophila.

Daily changes in GFAP expression in radial glia of the olfactory bulb in rabbit pups entrained to circadian feeding

When food is restricted daily to a fixed time, animals show uncoupled molecular, physiological and behavioral circadian rhythms from those entrained by light and controlled by the suprachiasmatic nucleus. The loci of the food-entrainable oscillator and the mechanisms by which rhythms emerge are unclear. Using animals entrained to the light-dark cycle, recent studies indicate that astrocytes in the suprachiasmatic nucleus play a key role in the regulation of circadian rhythms. However, it is unknown whether astrocytic cells can be synchronized by circadian restricted feeding. Studying the olfactory bulb (OB) of rabbit pups entrained to daily feeding, we hypothesized that the expression of glial fibrillary acidic protein (GFAP) and the morphology of GFAP-immunopositive cells change in synchrony with timing of feeding. By using pups fed at 1000 h or 2200 h, we found that GFAP protein expression in the OB changes with a nadir at feeding time and a peak 16 h after feeding. We also found that length of radial glia processes, the most abundant GFAP+ cell in the rabbit pup OB, shows a daily change also coupled to feeding time. These temporal changes of GFAP were expressed in anti-phase to the rhythms of locomotor activity and c-Fos immunoreactivity. The results indicate that GFAP expression and elongation-retraction of radial glia processes are coupled by feeding time and suggest that glia cells may play an important functional role in food entraining of the OB circadian oscillator.

Chronically skipping breakfast impairs hippocampal memory-related gene expression and memory function accompanied by reduced wakefulness and body temperature in mice

Acute or chronic effects of consuming or skipping breakfast on cognitive performance in humans are controversial. To evaluate the effects of chronically skipping breakfast (SB) on hippocampus-dependent long-term memory formation, we examined hippocampal gene expression and applied the novel object recognition test (NORT) after two weeks of repeated fasting for six hours from lights off to mimic SB in mice. We also examined the effects of SB on circadian rhythms of locomotor activity, food intake, core body temperature (CBT) and sleep-wake cycles. Skipping breakfast slightly but significantly decreased total daily food intake without affecting body weight gain. Locomotor activity and CBT significantly decreased during the fasting period under SB. The degree of fasting-dependent CBT reduction gradually increased and then became stabilized after four days of SB. Electroencephalographic data revealed that repeated SB significantly decreased the duration of wakefulness and increased that of rapid eye movement (REM) and of non-REM (NREM) sleep during the period of SB. Furthermore, total daily amounts of wakefulness and NREM sleep were significantly decreased and increased, respectively, under SB, suggesting that SB disrupts sleep homeostasis. Skipping breakfast significantly suppressed mRNA expression of the memory-related genes, Camk2a, Fkbp5, Gadd45b, Gria1, Sirt1 and Tet1 in the hippocampus. Recognition memory assessed by NORT was impaired by SB in accordance with the gene expression profiles. These findings suggested that chronic SB causes dysregulated CBT, sleep-wake cycles and hippocampal gene expression, which results in impaired long-term memory formation.

A Homeobox Transcription Factor Scarecrow (SCRO) Negatively Regulates Pdf Neuropeptide Expression through Binding an Identified cis-Acting Element in Drosophila melanogaster.

In Drosophila, transcriptional feedback loops contribute to intracellular timekeeping mechanisms responsible for daily rhythms. Pigment-dispersing factor (PDF) is the major neuropeptide produced by latero-ventral neurons (LNvs) that function as a central pacemaker for circadian locomotor activity rhythms. PDF synchronizes other clock neurons thereby playing an essential role in the maintenance and coordination of circadian locomotor rhythms. However, the underlying molecular mechanism of the LNvs-specific Pdf expression is not well understood. Here, using Pdf promoter-bashing experiment, we identified a cis-acting Pdf regulatory element (PRE) that is sufficient for driving Pdf expression in the LNvs. We have also identified a homeobox transcription factor, scarecrow (SCRO), as a direct binding factor to PRE. Furthermore, transgenic expression of scro in the clock neurons abolished Pdf expression and circadian locomotor activity rhythms, and such repressive function requires DNA-binding homeodomain, but none of the other conserved domains. scro is predominantly expressed in the optic lobe and various clusters of cells in other areas of the central nervous system. A homozygous scro-null mutant generated by CRIPSR is lethal during embryonic and early larval development, suggesting that scro plays a vital role during early development.

Effect of season and sex on the locomotor activity rhythm of the desert isopod Hemilepistus reamurii

ABSTRACT Freshly collected individuals of Hemilepistus reaumurii from the marginal zone of a salt lake in Bchachma (Middle of Tunisia) were seasonally housed in a controlled environment cabinet. The aim of this study was to investigate the effect of sex on the locomotor activity rhythm of this species. Locomotor activity rhythm of males and females of this species was recorded during each season under light-dark cycle (nLD) at a constant temperature of 18 ± 0.5°C. Results showed that both males and females of H. reaumurii exhibited a day activity in late winter and in spring and a crepuscular activity during the other seasons. Results showed also that the locomotor rhythms of males and females were controlled by an endogenous component with circadian period. Furthermore, locomotor rhythm was more stable and better defined in males than in females during spring under constant darkness. The most important locomotor activity time (α) was recorded in winter and spring whatever the sex. However, our finding demonstrated that males were more active than females in late winter. On the other hand, females were more active than males during spring. The variation of activity patterns according to the sexes and seasons is discussed.

Responses of activity rhythms to temperature cues evolve in Drosophila populations selected for divergent timing of eclosion.

Even though the rhythms in adult emergence and locomotor activity are two different phenomena that occur at distinct life stages of the fly life cycle, previous studies have hinted at similarities in certain aspects of the organisation of the circadian clock driving these two rhythms. For instance, the period gene plays an important regulatory role in both rhythms. In an earlier study, we have shown that selection on timing of adult emergence behaviour in populations of Drosophila melanogaster leads to the co-evolution of temperature sensitivity of circadian clocks driving eclosion. In this study, we investigated whether temperature sensitivity of the locomotor activity rhythm evolved in our populations separately from the adult emergence rhythm, with the goal of understanding the extent of similarity (or lack thereof) in circadian organisation underlying the two rhythms. We found that in response to simulated jetlag with temperature cycles, late chronotypes (populations selected for predominant emergence during dusk) indeed re-entrained faster than early chronotypes (populations selected for predominant emergence during dawn) to 6 h phase delays, thereby indicating enhanced sensitivity of the activity/rest clock to temperature cues in these stocks (entrainment is the synchronisation of internal rhythms to cyclic environmental time cues). Additionally, we found that late chronotypes show higher plasticity of phases across regimes, day-to-day stability in phases and amplitude of entrainment, all indicative of enhanced temperature-sensitive activity/rest rhythms. Our results highlight remarkably similar organisation principles between circadian clocks regulating emergence and activity/rest rhythms.

Decreased circadian fluctuation in cognitive behaviors and synaptic plasticity in APP/PS1 transgenic mice.

Cognitive decline, memory impairment and circadian rhythm disturbance are iconic manifestations of Alzheimer's disease (AD). APPswe/PS1dE9 (APP/PS1) mice, a model of AD, show deficits in multiple learning and memory abilities, synaptic plasticity, and behavioral circadian rhythm, but whether circadian differences in cognitive performance and synaptic plasticity could be affected in AD remain unclear. Here, the cognitive behaviors of 6-month-old APP/PS1 mice were assessed by multiple behavior tests in the rest phase (light period) or active phase (dark period) of the day. The possible electrophysiological mechanism was subsequently investigated by in vivo hippocampal long-term potentiation (LTP) recording, and the locomotor activity rhythm of the mice was detected using wheel-running activities. Compared to wild-type (WT) mice, APP/PS1 mice exhibited long-term spatial memory impairment and in vivo hippocampal LTP suppression. In addition, in APP/PS1 mice, circadian differences in new object recognition memory and LTP were lost, and the circadian difference in long-term spatial memory was decreased, accompanied by a less robust locomotor activity rhythm. These results indicate that the loss of circadian differences in new object recognition memory and the decrease in the circadian difference in long-term spatial memory in APP/PS1 mice, which are closely associated with the loss of the circadian difference in LTP and less robust locomotor activity, might occur early in the course of AD.

Daily rhythms in food intake and locomotor activity in a colony of domestic cats

BackgroundDaily rhythms have been widely investigated in various mammals but, surprisingly, literature is scarce and conflicting regarding the domestic cat, Felis catus. This may come from the difficulty to analyse rhythms in a species showing high interindividual variability and from the common idea that the rhythms of the cat are rather random. To elucidate the subject, two groups of indoor cats (14 in total) living in a cattery room, were followed on a 24 h/7 day basis, using advanced telemetry technologies, i.e. passive RFID, automated weighing of electronic scales and UWB technology with accuracy ensuring a good reliability of the results.ResultsWhile covering on average 1.74 ± 0.4 km and eating 46.4 ± 3.6 g (≈ 179 kcal) of dry food per day, findings indicate 24 h periodicity in the locomotor and feeding rhythms of the cats. Systematically, their locomotor behaviour was more rhythmic than their eating behaviour (p < 0.01), possibly reflecting the flexibility of the eating patterns of the cat initially enabling it to adapt to daily rhythms of its prey. In their daily patterns, the indoor individuals showed two main troughs of activity and food intake—in the middle of the day and in the middle of the night—and two main peaks: one in the morning (especially before sunrise and food renewal), the other in the evening (following the end of the work day of the animal staff and before sunset), supporting previous work demonstrating peaks at dusk and dawn and confirming the crepuscular nature of the species. No general pattern emerged according to a more nocturnal versus diurnal organisation.ConclusionsBimodality, more than chronotypes, seems therefore to best characterise the activity and feeding rhythms of the species as it was demonstrated in the individuals among the different categorisations. By validating the use of new tracking technologies as well as of adapted chronobiological parameters to assess the daily rhythm of cats living indoors, this study opens the way for more adequate analyses of cat behaviour through time under various conditions.

Circadian learning and memory changes in Aβ1-42 induced Alzheimer's mice.

Alzheimer disease (AD) is a growing health problem globally, which causes a progressive decline in learning and memory and multiple disturbances of circadian rhythms. Six Alzheimer's mice and six wild type (WT) mice were involved in this study. Morris Water Maze (MWM) tasks were conducted hourly to evaluate their circadian learning and memory performance. We used a single cosinor-based method to evaluate the circadian learning and memory of Alzheimer's mice and WT mice, respectively. An area sensor was used to record locomotor activity for 2weeks continuously, including 7days of 12h light/12h dark (LD) conditions and 7days of 12h dark/12h dark (DD) conditions. All WT mice showed circadian rhythm presence in learning and memory, and the peak of escape latency appeared at circadian time (CT) 12. Only one in six Alzheimer's mice showed a circadian rhythm, but the peak of escape latency was postponed to CT20. Alzheimer's mice showed rhythm absence under LD or DD conditions. Under LD conditions, the WT mice activity was higher than that in the Alzheimer's mice during ZT0-5 (p = 0.007) and ZT18-23 (p = 0.353) but lower during ZT6-11 (p < 0.001) and ZT12-17 (p < 0.001). Learning and memory of wild type mice is proved to have a circadian variation throughout a day. In Alzheimer's mice, rhythmic locomotor activity and circadian learning and memory performance were disrupted. Understanding the role of rhythmic disturbances in the process of AD may assist to identify therapeutic targets.

Tinkering with day length disrupts reproductive diapause

I always feel a little sad when I have to start putting on the lights almost as soon as I get home at the end of the day, but shorter day lengths signify a far more dramatic lifestyle change for many other species. When the number of hours of daylight falls too low, many northern insects place their reproductive systems into suspended animation – known as reproductive diapause – to wait out winter. Some species fine-tune the timing of the switch depending on their latitude, with females from higher latitudes triggering reproductive diapause when the days are longer than those in more southern locations. Yet, how insects synchronize the physiological processes that must be coordinated to harmonise their physiology with the seasons, remained a mystery.With a long-standing interest in how insects predict the onset of winter, Anneli Hoikkala from the University of Jyväskylä, Finland – with colleagues from her university, Oulu University, Finland, and St Andrews, UK – took advantage of the insect's versatility. They artificially evolved populations of Drosophila montana, collected in northern Finland by shortening the amount of daylight experienced by each subsequent generation by 0.5 h to begin unravelling the masterplan that coordinates the flies’ seasonal reproductive off switch. Once they were sure that the diapause trigger had been reprogrammed by the shorter day lengths, the team looked for differences between the new population and flies that had been maintained for generations on a daily schedule of 24 h light, simulating the northern summer.Presenting the new population with days where the number of hours of light varied from 13–21 h over a 24 h period, Hannele Kauranen and Johanna Kinnunen found that 50% of the females went into diapause when they had 17.5 h of light, in contrast to their northerly ancestors, which initiated reproductive diapause at 19.4 h. Then Pekka Lankinen tinkered with the length of the full day – fixing the amount of daylight at 12 h while varying the length of the night from 6 to 72 h – he found that their internal body clocks – circadian rhythms – were not contributing to triggering the flies’ reproductive shut down.Having checked factors that could activate reproductive diapause, the team knew that the wild insects tend to bear cold better as the days draw in, so Anna-Lotta Hiillos measured the temperature at which the evolved flies toppled into a coma when it became too cold. She found that females from the evolved population that had gone into diapause were only able to able to tolerate temperatures down to around –1.8°C while the flies that had experienced normal 24 h days across the generations were able to hold out to –2.2°C; the evolved flies were less cold tolerant. Finally Axel Wiberg and Michael Ritchie analysed the flies’ genome to search for differences that could explain the reproductive diapause shift and found changes in genes involved in the insect's ability to sense light, their hormone signalling, growth and egg development. ‘Overall, our study shows that photoperiodic selection for reproduction under short photoperiods affects diapause-associated traits without disrupting the central clock network generating circadian rhythms in fly locomotor activity’, says Kauranen.

Optimizing rearing and welfare in Senegalese sole (Solea senegalesensis) broodstock: Effect of ambient light intensity and handling time on stress response

Broodstock rearing conditions and handling procedures should be optimized in aquaculture species in order to benefit fish welfare and guarantee optimal conditions for spawning. In teleosts, basal cortisol levels display daily rhythms, oscillating along the 24 h of the day. In this sense, handling fish at different moments of the day may lead to different stress responses. The present study aimed at investigating the optimal rearing conditions for Senegalese sole broodstock, considering ambient light intensity and handling time. The optimal light intensity (50, 100 or 200 lx) was investigated by measuring fish cortisol levels and monitoring locomotor activity rhythms under each intensity tested. Results showed a significant increase in cortisol levels of fish exposed to 200 lx, when compared to values obtained under 100 lx, accompanied by changes in locomotor activity rhythms in both tanks under study. These results suggested that 200 lx may be too high as light intensity for this species, whereas 100 lx seems to be more adequate. Also, daily rhythms of stress response were investigated in breeders from different origins (Wild and first generation, G1). Basal cortisol levels and cortisol stress response after an acute stressor (air exposure) were monitored at two distinct moments of the day (Mid-Light and Mid-Dark). Basal levels were higher during the day in the wild group, while G1 fish seemed to have lost the daily fluctuations in basal cortisol plasma levels, as well as their daily rhythms of locomotor activity. Both groups showed lower stress responses during night-time, an indication that this is an adequate period of the day to handle this species. Senegalese sole breeders born in captivity presented more pronounced stress responses when compared to wild fish, reflecting their different life history in terms of stress challenges.

Short- and long-duration exposures to cell-phone radiofrequency waves produce dichotomous effects on phototactic response and circadian characteristics of locomotor activity rhythm in zebrafish, Danio rerio

ABSTRACT We examined the effects of short- and long-duration exposure to cell phone radiation (CPR) on phototactic response (PR) and circadian characteristics of locomotor-activity rhythm, respectively, in zebrafish. We exposed four groups (10 in each) randomly selected fish to CPR emitted by a 2300 MHz 4G cell phone for 0.5 h, 1 h, 2 h, 3 h, and 4 h duration at two different time points of a day, i.e. morning and evening, to assess the PR. We also studied the effects of 1 week CPR exposure on circadian rhythm in locomotor activity pattern in eight singly housed zebrafish. We had eight singly housed sham-exposed zebrafish as the control. Results of two-way ANOVA revealed statistically significant effects of the factors exposure time and exposure duration on the PR of zebrafish. Fish exhibited photo-positive response till 2 h following morning exposure, and thereafter, showed photo-negative response with increased duration of exposure. During evening exposure, the fish were mostly photo-negative. However, 1 week exposure to CPR did not produce any significant effects on the circadian characteristics of locomotor activity rhythm. It is concluded that the CPR might alter phototaxis, but not the parameters of circadian rhythm in locomotor activity pattern of zebrafish.

The effects of artificial light at night on Eurasian tree sparrow (Passer montanus): Behavioral rhythm disruption, melatonin suppression and intestinal microbiota alterations

Abstract Artificial light at night (ALAN) or light pollution is rapidly widespread with fast urbanization and becomes an obvious environmental disturbance. Recent studies showed ALAN has multiple negative impacts on a wide range of species including bird biological rhythm disruption, behavioral and physiological disturbance and hormone secretion disorder. However, its effects on bird gut microbiota are scarcely studied. In this study, we used Eurasian tree sparrow (Passer montanus), a widely distributed and locally abundant bird species in both urban and rural areas of China to examine the effects of ALAN on locomotor activity rhythm and melatonin secretion, and species diversity and community structure of intestinal microbiota by simulating urban and rural night light environment. Our results showed ALAN strongly affected circadian rhythm of locomotor activity with earlier start of activity before light-on and later rest after light-off. Moreover, ALAN significantly suppressed melatonin release. Last but not least, ALAN profoundly affected taxonomic compositions, species diversity and community structure of intestinal microbiota of birds. We concluded that ALAN may cause bird health damage by disrupting circadian rhythm, inhibiting melatonin release and altering intestinal microbiota. Melatonin hormone level and intestinal microbiota diversity may be important bioindicators for light pollution.

Removing Short Wavelengths From Polychromatic White Light Attenuates Circadian Phase Resetting in Rats.

Visible light is the principal stimulus for resetting the mammalian central circadian pacemaker. Circadian phase resetting is most sensitive to short-wavelength (blue) visible light. We examined the effects of removing short-wavelengths < 500 nm from polychromatic white light using optical filters on circadian phase resetting in rats. Under high irradiance conditions, both long- (7 h) and short- (1 h) duration short-wavelength filtered (< 500 nm) light exposure attenuated phase-delay shifts in locomotor activity rhythms by (∼40–50%) as compared to unfiltered light exposure. However, there was no attenuation in phase resetting under low irradiance conditions. Additionally, the reduction in phase-delay shifts corresponded to regionally specific attenuation in molecular markers of pacemaker activation in response to light exposure, including c-FOS, Per1 and Per2. These results demonstrate that removing short-wavelengths from polychromatic white light can attenuate circadian phase resetting in an irradiance dependent manner. These results have important implications for designing and optimizing lighting interventions to enhance circadian adaptation.

Estradiol treatment improves biological rhythms in a preclinical rat model of menopause

The perimenopausal transition at middle age is often associated with hot flashes and sleep disruptions, metabolic changes, and other symptoms. Whereas the mechanisms for these processes are incompletely understood, both aging (AG) and a loss of ovarian estrogens play contributing roles. Furthermore, the timing of when estradiol (E) treatment should commence and for how long are key clinical questions in the management of symptoms. Using a rat model of surgical menopause, we determined the effects of regimens of E treatment with differing time at onset and duration of treatment on diurnal rhythms of activity and core temperature and on food intake and body weight. Reproductively mature (MAT, ∼4 months) or AG (∼11 months) female rats were ovariectomized, implanted intraperitoneally with a telemetry device, and given either a vehicle (V) or E subcutaneous capsule implantation. Rats were remotely recorded for 10 days per month for 3 (MAT) or 6 (AG) months. To ascertain whether delayed onset of treatment affected rhythms, a subset of AG-V rats had their capsules switched to E at the end of 3 months. Another set of AG-E rats had their capsules removed at 3 months to determine whether beneficial effects of E would persist. Overall, activity and temperature mesor, robustness, and amplitude declined with AG. Compared to V treatment, E-treated rats showed (1) better maintenance of body weight and food intake; (2) higher, more consolidated activity and temperature rhythms; and (3) higher activity and temperature robustness and amplitude. In the AG arm of the study, switching treatment from V to E or E to V quickly reversed these patterns. Thus, the presence of E was the dominant factor in determining stability and amplitude of locomotor activity and temperature rhythms. As a whole, the results show benefits of E treatment, even with a delay, on biological rhythms and physiological functions.

Effects of a semi-chronic exposition to Paraquat and Maneb on the circadian rhythm of locomotor activity in Wistar rats

Effects of a semi-chronic exposition to Paraquat and Maneb on the circadian rhythm of locomotor activity in Wistar rats

Behavioral and physiological processes in horses and their linkage with peripheral clock gene expression: A preliminary study

Behavioral and physiological processes have an innate 24-h cycle driven by the circadian master clock, which uses clock genes to generate rhythmicity and distribute temporal signals. Elucidating the blood gene expression in relation to the better known circadian rhythms in horses may contribute to improve the knowledge on the peripheral circadian rhythm control in this species. To do that, seven clinically healthy Italian saddle female horses were housed in individual boxes under natural photoperiod and environmental conditions. In each horse, locomotor activity was recorded continuously; blood samples and rectal temperature were recorded every 4 hours over a 48-hour period. To investigate the peripheral clock in horses, quantitative real-time RT polymerase chain reaction assays were designed to detected clock gene levels (Per 1, Per 2, and Cry 1) from blood samples. Blood cortisol serum level was also measured. Our results showed a daily expression of Per 1, Per 2, and Cry 1 in peripheral blood, associated with the daily rhythm of locomotor activity, rectal temperature and cortisol. In particular, a similar acrophase was observed for locomotor activity and Per 1; and for rectal temperature and Per 2. Rectal temperature and Per 2 also showed the same percentage of robustness of rhythm. We suggest the existence of a linkage between the peripheral clock genes Per 1 and Per 2 with locomotor activity and rectal temperature, although more studies are necessary to establish the exact mechanism of the peripheral clock.

Hypothalamic leptin sensitivity and health benefits of time-restricted feeding are dependent on the time of day in male mice.

Synchronization between biologic clocks and metabolism is crucial for most species. Here, we examined the ability of leptin, important in the control of energy metabolism, to induce leptin signaling at the molecular as well as the behavioral level throughout the 24-h day in mice fed either a control or a high-fat diet (HFD). Furthermore, we investigated the effects of time-restricted feeding (TRF; a limitation of HFD access to 6 h each day) on energy metabolism during different periods throughout the 24-h day. In control mice, molecular leptin sensitivity was highest at zeitgeber time (ZT)0 (lights on), declining during the light phase, and increasing during the dark phase. Surprisingly, leptin resistance in HFD-fed mice was only present from the middle of the dark to the middle of the light period. Specifically, when TRF occurred from ZT21 to ZT3 (when leptin resistance in HFD-fed mice was most profound), it resulted in a disruption of the daily rhythms of locomotor activity and energy expenditure and in increased plasma insulin levels compared with other TRF periods. These data provide evidence that leptin sensitivity is controlled by the circadian rhythm and that TRF periods may be most efficient when aligned with the leptin-sensitive period.-Boucsein, A., Rizwan, M. Z., Tups, A. Hypothalamic leptin sensitivity and health benefits of time-restricted feeding are dependent on the time of day in male mice.

Circadian dysfunction in the Q175 model of Huntington's disease: Network analysis.

Disturbances in sleep/wake cycle are a common complaint of individuals with Huntington's disease (HD) and are displayed by HD mouse models. The underlying mechanisms, including the possible role of the circadian timing system, have been the topic of a number of recent studies. The (z)Q175 mouse is a knock-in model in which the human exon 1 sequence of the huntingtin gene is inserted into the mouse DNA with approximately 190 CAG repeats. Among the numerous models available, the heterozygous Q175 offers strong construct validity with a single copy of the mutation, genetic precision of the insertion and control of mutation copy number. In this review, we will summarize the evidence that this model exhibits disrupted diurnal and circadian rhythms in locomotor activity. We found overwhelming evidence for autonomic dysfunction including blunted daily rhythms in heart rate and core body temperature (CBT), reduced heart rate variability, and almost a complete failure of the sympathetic arm of the autonomic nervous system to function during the baroreceptor reflex. Mechanistically, the Q175 mouse model exhibits deficits in the neural output of the central circadian clock, the suprachiasmatic nucleus along with an enhancement of at least one type of potassium current in these neurons. Finally, we report a novel network analysis examining the phase coherence between activity, CBT, and cardiovascular measures. Such analyses found that even young Q175 mutants (heterozygous or homozygous) show coherence degradation, and suggests that loss of phase coherence is a variable that should be considered as a possible biomarker for HD.

Host circadian rhythms are disrupted during malaria infection in parasite genotype-specific manners

Infection can dramatically alter behavioural and physiological traits as hosts become sick and subsequently return to health. Such “sickness behaviours” include disrupted circadian rhythms in both locomotor activity and body temperature. Host sickness behaviours vary in pathogen species-specific manners but the influence of pathogen intraspecific variation is rarely studied. We examine how infection with the murine malaria parasite, Plasmodium chabaudi, shapes sickness in terms of parasite genotype-specific effects on host circadian rhythms. We reveal that circadian rhythms in host locomotor activity patterns and body temperature become differentially disrupted and in parasite genotype-specific manners. Locomotor activity and body temperature in combination provide more sensitive measures of health than commonly used virulence metrics for malaria (e.g. anaemia). Moreover, patterns of host disruption cannot be explained simply by variation in replication rate across parasite genotypes or the severity of anaemia each parasite genotype causes. It is well known that disruption to circadian rhythms is associated with non-infectious diseases, including cancer, type 2 diabetes, and obesity. Our results reveal that disruption of host circadian rhythms is a genetically variable virulence trait of pathogens with implications for host health and disease tolerance.