Loss Of Synchrony Research Articles

Serotonin Drives Predatory Feeding Behavior via Synchronous Feeding Rhythms in the Nematode Pristionchus pacificus

Feeding behaviors in a wide range of animals are regulated by the neurotransmitter serotonin, although the exact neural circuits and associated mechanism are often unknown. The nematode Pristionchus pacificus can kill other nematodes by opening prey cuticles with movable teeth. Previous studies showed that exogenous serotonin treatment induces a predatory-like tooth movement and slower pharyngeal pumping in the absence of prey; however, physiological functions of serotonin during predation and other behaviors in P. pacificus remained completely unknown. Here, we investigate the roles of serotonin by generating mutations in Ppa-tph-1 and Ppa-bas-1, two key serotonin biosynthesis enzymes, and by genetic ablation of pharynx-associated serotonergic neurons. Mutations in Ppa-tph-1 reduced the pharyngeal pumping rate during bacterial feeding compared with wild-type. Moreover, the loss of serotonin or a subset of serotonergic neurons decreased the success of predation, but did not abolish the predatory feeding behavior completely. Detailed analysis using a high-speed camera revealed that the elimination of serotonin or the serotonergic neurons disrupted the timing and coordination of predatory tooth movement and pharyngeal pumping. This loss of synchrony significantly reduced the efficiency of successful predation events. These results suggest that serotonin has a conserved role in bacterial feeding and in addition drives the feeding rhythm of predatory behavior in Pristionchus.

When to eat? The influence of circadian rhythms on metabolic health: are animal studies providing the evidence?

As obesity and metabolic diseases rise, there is need to investigate physiological and behavioural aspects associated with their development. Circadian rhythms have a profound influence on metabolic processes, as they prepare the body to optimise energy use and storage. Moreover, food-related signals confer temporal order to organs involved in metabolic regulation. Therefore food intake should be synchronised with the suprachiasmatic nucleus (SCN) to elaborate efficient responses to environmental challenges. Human studies suggest that a loss of synchrony between mealtime and the SCN promotes obesity and metabolic disturbances. Animal research using different paradigms has been performed to characterise the effects of timing of food intake on metabolic profiles. Therefore the purpose of the present review is to critically examine the evidence of animal studies, to provide a state of the art on metabolic findings and to assess whether the paradigms used in rodent models give the evidence to support a 'best time' for food intake. First we analyse and compare the current findings of studies where mealtime has been shifted out of phase from the light-dark cycle. Then, we analyse studies restricting meal times to different moments within the active period. So far animal studies correlate well with human studies, demonstrating that restricting food intake to the active phase limits metabolic disturbances produced by high-energy diets and that eating during the inactive/sleep phase leads to a worse metabolic outcome. Based on the latter we discuss the missing elements and possible mechanisms leading to the metabolic consequences, as these are still lacking.

The Circadian System: A Regulatory Feedback Network of Periphery and Brain.

Circadian rhythms are generated by the autonomous circadian clock, the suprachiasmatic nucleus (SCN), and clock genes that are present in all tissues. The SCN times these peripheral clocks, as well as behavioral and physiological processes. Recent studies show that frequent violations of conditions set by our biological clock, such as shift work, jet lag, sleep deprivation, or simply eating at the wrong time of the day, may have deleterious effects on health. This infringement, also known as circadian desynchronization, is associated with chronic diseases like diabetes, hypertension, cancer, and psychiatric disorders. In this review, we will evaluate evidence that these diseases stem from the need of the SCN for peripheral feedback to fine-tune its output and adjust physiological processes to the requirements of the moment. This feedback can vary from neuronal or hormonal signals from the liver to changes in blood pressure. Desynchronization renders the circadian network dysfunctional, resulting in a breakdown of many functions driven by the SCN, disrupting core clock rhythms in the periphery and disorganizing cellular processes that are normally driven by the synchrony between behavior and peripheral signals with neuronal and humoral output of the hypothalamus. Consequently, we propose that the loss of synchrony between the different elements of this circadian network as may occur during shiftwork and jet lag is the reason for the occurrence of health problems.

Hippocampal CA1 Ripples as Inhibitory Transients.

Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.

Targeting engineering synchronization in chaotic systems

A method of targeting engineering synchronization states in two identical and mismatch chaotic systems is explained in detail. The method is proposed using linear feedback controller coupling for engineering synchronization such as mixed synchronization, linear and nonlinear generalized synchronization and targeting fixed point. The general form of coupling design to target any desire synchronization state under unidirectional coupling with the help of Lyapunov function stability theory is derived analytically. A scaling factor is introduced in the coupling definition to smooth control without any loss of synchrony. Numerical results are done on two mismatch Lorenz systems and two identical Sprott oscillators.

Kuramoto Phase Model with Inertia: Bifurcations Leading to the Loss of Synchrony and to the Emergence of Chaos

We consider a finite-dimensional model of phase oscillators with inertia in the case of star configuration of coupling. The system of equations is reduced to a nonlinearly coupled system of pendulum equations. We prove that the transition from synchronous to asynchronous oscillations occurs via bifurcation of saddle-node equilibrium. In this connection the asynchronous regime can be partially synchronous rotations. We find that the reverse transition from asynchronous to synchronous regime occurs via bifurcation of homoclinic orbit both of the saddle equilibrium point and of the saddle periodic orbit. In the case of homoclinic loop of the saddle point the synchrony appears only from asynchronous mode without partially synchronized rotations. In the case of the homoclinic curve of the saddle periodic orbit the system undergoes a chaotic rotation regime which results in a random return to synchrony. We establish that return transitions are hysteretic in the case of large inertia.

Oscillations or Synchrony? Disruption of Neural Synchrony despite Enhanced Gamma Oscillations in a Model of Disrupted Perceptual Coherence.

It has been hypothesized that neural synchrony underlies perceptual coherence. The hypothesis of loss of central perceptual coherence has been proposed to be at the origin of abnormal cognition in autism spectrum disorders and Williams syndrome, a neurodevelopmental disorder linked with autism, and a clearcut model for impaired central coherence. We took advantage of this model of impaired holistic processing to test the hypothesis that loss of neural synchrony plays a separable role in visual integration using EEG and a set of experimental tasks requiring coherent integration of local elements leading to 3-D face perception. A profound reorganization of brain activity was identified. Neural synchrony was reduced across stimulus conditions, and this was associated with increased amplitude modulation at 25-45 Hz. This combination of a dramatic loss of synchrony despite increased oscillatory activity is strong evidence that synchrony underlies central coherence. This is the first time, to our knowledge, that dissociation between amplitude and synchrony is reported in a human model of impaired perceptual coherence, suggesting that loss of phase coherence is more directly related to disruption of holistic perception.

Meat Feeding Restricts Rapid Cold Hardening Response and Increases Thermal Activity Thresholds of Adult Blow Flies, Calliphora vicina (Diptera: Calliphoridae).

Virtually all temperate insects survive the winter by entering a physiological state of reduced metabolic activity termed diapause. However, there is increasing evidence that climate change is disrupting the diapause response resulting in non-diapause life stages encountering periods of winter cold. This is a significant problem for adult life stages in particular, as they must remain mobile, periodically feed, and potentially initiate reproductive development at a time when resources should be diverted to enhance stress tolerance. Here we present the first evidence of protein/meat feeding restricting rapid cold hardening (RCH) ability and increasing low temperature activity thresholds. No RCH response was noted in adult female blow flies (Calliphora vicina Robineau-Desvoidy) fed a sugar, water and liver (SWL) diet, while a strong RCH response was seen in females fed a diet of sugar and water (SW) only. The RCH response in SW flies was induced at temperatures as high as 10°C, but was strongest following 3h at 0°C. The CTmin (loss of coordinated movement) and chill coma (final appendage twitch) temperature of SWL females (-0.3 ± 0.5°C and -4.9 ± 0.5°C, respectively) was significantly higher than for SW females (-3.2 ± 0.8°C and -8.5 ± 0.6°C). We confirmed this was not directly the result of altered extracellular K+, as activity thresholds of alanine-fed adults were not significantly different from SW flies. Instead we suggest the loss of cold tolerance is more likely the result of diverting resource allocation to egg development. Between 2009 and 2013 winter air temperatures in Birmingham, UK, fell below the CTmin of SW and SWL flies on 63 and 195 days, respectively, suggesting differential exposure to chill injury depending on whether adults had access to meat or not. We conclude that disruption of diapause could significantly impact on winter survival through loss of synchrony in the timing of active feeding and reproductive development with favourable temperature conditions.

Reflections on 20 years of RNA folding, dynamics, and structure.

Reflections on 20 years of RNA folding, dynamics, and structure.

Control of partial synchronization in chaotic oscillators

A design of coupling is proposed to control partial synchronization in two chaotic oscillators in a driver–response mode. A control of synchrony between one response variables is made possible (a transition from a complete synchronization to antisynchronization via amplitude death and vice versa without loss of synchrony) keeping the other pairs of variables undisturbed in their pre-desired states of coherence. Further, one of the response variables can be controlled so as to follow the dynamics of an external signal (periodic or chaotic) while keeping the coherent status of other variables unchanged. The stability of synchronization is established using the Hurwitz matrix criterion. Numerical example of an ecological foodweb model is presented. The control scheme is demonstrated in an electronic circuit of the Sprott system.

Diurnal oscillation of amygdala clock gene expression and loss of synchrony in a mouse model of depression.

Background:Disturbances in circadian rhythm-related physiological and behavioral processes are frequently observed in depressed patients and several clock genes have been identified as risk factors for the development of mood disorders. However, the particular involvement of the circadian system in the pathophysiology of depression and its molecular regulatory interface is incompletely understood.Methods:A naturalistic animal model of depression based upon exposure to chronic mild stress was used to induce anhedonic behavior in mice. Micro-punch dissection was used to isolate basolateral amygdala tissue from anhedonic mice followed by quantitative real-time PCR–based analysis of gene expression.Results:Here we demonstrate that chronic mild stress-induced anhedonic behavior is associated with disturbed diurnal oscillation of the expression of Clock, Cry2, Per1, Per3, Id2, Rev-erbα, Ror-β and Ror-γ in the mouse basolateral amygdala. Clock gene desynchronization was accompanied by disruption of the diurnal expressional pattern of vascular endothelial growth factor A expression in the basolateral amygdala of anhedonic mice, also reflected in alterations of circulating vascular endothelial growth factor A levels.Conclusion:We propose that aberrant control of diurnal rhythmicity related to depression may indeed directly result from the illness itself and establish an animal model for the further exploration of the molecular mechanisms mediating the involvement of the circadian system in the pathophysiology of mood disorders.

Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant.

In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus (SCN) to circadian behavior and the organization of peripheral clocks, we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines. The forebrain knockout mice showed >90% deletion of BMAL1 in the SCN and exhibited an immediate and complete loss of circadian behavior in constant conditions. Circadian rhythms in peripheral tissues persisted but became desynchronized and damped in constant darkness. The loss of synchrony was rescued by light/dark cycles and partially by restricted feeding (only in the liver and kidney but not in the other tissues) in a distinct manner. These results suggest that the forebrain/SCN is essential for internal temporal order of robust circadian programs in peripheral clocks, and that individual peripheral clocks are affected differently by light and feeding in the absence of a functional oscillator in the forebrain.

Time-delay effects on the aging transition in a population of coupled oscillators.

We investigate the influence of time-delayed coupling on the nature of the aging transition in a system of coupled oscillators that have a mix of active and inactive oscillators, where the aging transition is defined as the gradual loss of collective synchrony as the proportion of inactive oscillators is increased. We start from a simple model of two time-delay coupled Stuart-Landau oscillators that have identical frequencies but are located at different distances from the Hopf bifurcation point. A systematic numerical and analytic study delineates the dependence of the critical coupling strength (at which the system experiences total loss of synchrony) on time delay and the average distance of the system from the Hopf bifurcation point. We find that time delay can act to facilitate the aging transition by lowering the threshold coupling strength for amplitude death in the system. We then extend our study to larger systems of globally coupled active and inactive oscillators including an infinite system in the thermodynamic limit. Our model system and results can provide a useful paradigm for understanding the functional robustness of diverse physical and biological systems that are prone to aging transitions.

Synchrony analysis: application in early diagnosis, staging and prognosis of multiple sclerosis

Multiple Sclerosis (MS) is an autoimmune disease caused by degeneration of the myelin sheath of large diameter fibers in the central nervous system. This will cause deficits in the conducting properties of nerves and also affect electrical signaling. As a result, in MS patients, nerve conduction will be slower than normal (Kandel et al., 2000). Neural synchrony has been of great interest in neuroscience recently. In signal processing, synchrony refers to quantifying similarity, coherence or correlation among signals and could be measured using a variety of methods (Dauwels et al., 2010). Neural synchrony represents how synchronous the neurons are firing (Vialatte et al., 2008). It is proven that synchrony is an important feature of brain signals. Many neurological diseases are accompanied by abnormalities in neural synchrony (Dauwels et al., 2008). For example, loss of synchrony among brain signals has been observed in disorders such as Parkinson's and Alzheimer's disease (AD) and was used for the purpose of diagnosis. On the other hand, increasing synchrony has been reported in disorders such as epileptic seizures (Vialatte et al., 2009). Since perturbation in electrical signaling and slowing of nerve conduction are common among MS and the aforementioned diseases, it brings up the idea of using synchrony for MS as well. In addition, previous works on MS have reported loss of connectivity and synchronous function among different parts of patients' brains. It should be mentioned that most of the previous works were concentrated on the cognitive impairments caused by the disease, and they applied their methods on MEG signals (Arrondo et al., 2009; Hardmeier et al., 2012). The other point which should be noted is that although MRI and ERP are both common tools in MS diagnosis and follow up, definite diagnosis cannot be made based on these criteria individually. In addition, MRI needs to be repeated (Greenberg et al., 2009; Longo et al., 2012) and it is not affordable and available in many situations. So, we should try to find a reliable solution. According to the aforementioned points, we believe that recording electrical brain signals (particularly EEG and ERP) and calculating local and global synchrony among their channels may provide us with an individual tool for diagnosing MS. Actually, the idea we put forward is using calculated synchrony indices for the purpose of detection, classification and prediction on electrical brain signals. Of course, the previous results which investigated connectivity and synchronous function of brain parts support our idea (Arrondo et al., 2009; Hardmeier et al., 2012). The proposed idea may also help us to detect MS in early stages. Additionally, we believe as impairments will increase by progression of the disease, synchrony measures may have significant differences in different stages of the disease. So, they could be useful for staging of the disease as well. We also propose measuring synchrony among brain signals in the onset periods. It seems that there should be a correlation between the changes in synchrony measures and disease prognosis. In better words, based on the calculated synchrony indices, we can predict the trend of the disease. This would provide us with a clearer perspective of the possible efficiency of different management modalities (including medical and surgical). Additionally, based on the potential level of neural dyssynchrony the proposed idea can be useful in order to assess the efficiency of the selected treatments for both the patient and the physician. Surely experimental evaluations are needed to validate our hypothesis.

Lag, lock, sync, slip: the many ‘phases’ of coupled flagella

In a multitude of life's processes, cilia and flagella are found indispensable. Recently, the biflagellated chlorophyte alga Chlamydomonas has become a model organism for the study of ciliary motility and synchronization. Here, we use high-speed, high-resolution imaging of single pipette-held cells to quantify the rich dynamics exhibited by their flagella. Underlying this variability in behaviour are biological dissimilarities between the two flagella—termed cis and trans, with respect to a unique eyespot. With emphasis on the wild-type, we derive limit cycles and phase parametrizations for self-sustained flagellar oscillations from digitally tracked flagellar waveforms. Characterizing interflagellar phase synchrony via a simple model of coupled oscillators with noise, we find that during the canonical swimming breaststroke the cis flagellum is consistently phase-lagged relative to, while remaining robustly phase-locked with, the trans flagellum. Transient loss of synchrony, or phase slippage, may be triggered stochastically, in which the trans flagellum transitions to a second mode of beating with attenuated beat envelope and increased frequency. Further, exploiting this alga's ability for flagellar regeneration, we mechanically induced removal of one or the other flagellum of the same cell to reveal a striking disparity between the beatings of the cis and trans flagella, in isolation. These results are evaluated in the context of the dynamic coordination of Chlamydomonas flagella.

On the classification of the cleavage patterns in amphibian embryos

This paper presents a brief survey and preliminary classification of embryonic cleavage patterns in the class Amphibia. We use published data on 41 anuran and 22 urodele species concerning the character of the third cleavage furrow (latitudinal or longitudinal) and the stage of transition from synchronous to asynchronous blastomere divisions in the animal hemisphere (4-8-celled stage, 8-16-celled stage or later). Based on this, four patterns of amphibian embryonic cleavage are recognized, and an attempt to elucidate the evolutionary relationships among these patterns is undertaken. The so-called "standard" cleavage pattern (the extensive series of synchronous blastomere divisions including latitudinal furrows of the third cleavage) with the typical model species Ambystoma mexicanum and Xenopus laevis seems to be derived and probably originated independently in the orders Anura and Caudata. The ancestral amphibian cleavage pattern seems to be represented by species with longitudinal furrows of the third cleavage and the loss ofsynchrony as early as the 8-celled stage (such as in primitive urodele species from the family Cryptobranchidae).

Combining optimization and machine learning techniques for genome-wide prediction of human cell cycle-regulated genes

The identification of cell cycle-regulated genes through the cyclicity of messenger RNAs in genome-wide studies is a difficult task due to the presence of internal and external noise in microarray data. Moreover, the analysis is also complicated by the loss of synchrony occurring in cell cycle experiments, which often results in additional background noise. To overcome these problems, here we propose the LEON (LEarning and OptimizatioN) algorithm, able to characterize the 'cyclicity degree' of a gene expression time profile using a two-step cascade procedure. The first step identifies a potentially cyclic behavior by means of a Support Vector Machine trained with a reliable set of positive and negative examples. The second step selects those genes having peak timing consistency along two cell cycles by means of a non-linear optimization technique using radial basis functions. To prove the effectiveness of our combined approach, we use recently published human fibroblasts cell cycle data and, performing in vivo experiments, we demonstrate that our computational strategy is able not only to confirm well-known cell cycle-regulated genes, but also to predict not yet identified ones. All scripts for implementation can be obtained on request.

Investigating the impact of the timing of blastulation on implantation: active management of embryo-endometrial synchrony increases implantation rates

Embryos that blastulate late have lower sustained implantation rates (SIR) than those blastulating on day 5 (D5). Traditionally attributed to reduced embryo quality, dyssynchrony with the endometrium is also possible. This study seeks to determine if the impaired implantation of slower embryos is intrinsic to the embryo or due to a loss of synchrony.

Fermitins, the Orthologs of Mammalian Kindlins, Regulate the Development of a Functional Cardiac Syncytium in Drosophila melanogaster

The vertebrate Kindlins are an evolutionarily conserved family of proteins critical for integrin signalling and cell adhesion. Kindlin-2 (KIND2) is associated with intercalated discs in mice, suggesting a role in cardiac syncytium development; however, deficiency of Kind2 leads to embryonic lethality. Morpholino knock-down of Kind2 in zebrafish has a pleiotropic effect on development that includes the heart. It therefore remains unclear whether cardiomyocyte Kind2 expression is required for cardiomyocyte junction formation and the development of normal cardiac function. To address this question, the expression of Fermitin 1 and Fermitin 2 (Fit1, Fit2), the two Drosophila orthologs of Kind2, was silenced in Drosophila cardiomyocytes. Heart development was assessed in adult flies by immunological methods and videomicroscopy. Silencing both Fit1 and Fit2 led to a severe cardiomyopathy characterised by the failure of cardiomyocytes to develop as a functional syncytium and loss of synchrony between cardiomyocytes. A null allele of Fit1 was generated but this had no impact on the heart. Similarly, the silencing of Fit2 failed to affect heart function. In contrast, the silencing of Fit2 in the cardiomyocytes of Fit1 null flies disrupted syncytium development, leading to severe cardiomyopathy. The data definitively demonstrate a role for Fermitins in the development of a functional cardiac syncytium in Drosophila. The findings also show that the Fermitins can functionally compensate for each other in order to control syncytium development. These findings support the concept that abnormalities in cardiomyocyte KIND2 expression or function may contribute to cardiomyopathies in humans.

Exercise strengthens circadian clocks

We all know that exercise can increase the strength of our muscles. In this issue of The Journal of Physiology, new research by Schroeder and colleagues (2012) demonstrates that exercise can also have a big impact on the circadian system, a network of structures that regulate daily rhythms in physiology. Circadian rhythms are maintained by precise cycles of molecular activity within cells. These cellular clocks are kept synchronized to the environment by a pacemaker structure deep in the brain, the suprachiasmatic nucleus. The suprachiasmatic nucleus normally keeps the body clock system in time by monitoring the external light–dark cycles and then imposing cycles of hormone release, body temperature, feeding, activity and many other functions. In some instances the signals from the suprachiasmatic nucleus are feeble, barely strong enough to keep the body clock system in order. This might occur when frequent jet lag or rotating shift work imposes light–dark signals that confuse the central pacemaker. Diminished pacemaker output signals are also observed in ageing and in some neurodegenerative disorders (Colwell, 2011). It is important to develop better treatments for these dampened pacemakers to allow strong daily modulation of physiology, especially in light of current research linking disrupted rhythms to diabetes, cancer progression, cardiovascular disease, mood disorders and a wide range of negative health consequences (Arendt, 2010). Fortunately, progress can be made using laboratory mice, which do not need fancy equipment or personal trainers to increase their level of exercise. Simply making a running wheel available will do the trick, as well as allow researchers to schedule the timing of when the running wheel is unlocked and free for use. In the present study, the investigators first demonstrated that free access to a running wheel can improve the power of diurnal rhythms. Further experiments investigated setting the time the wheel was available, either early (in the first 6 h) or late (in the latter 6 h) of the active phase. Mice undertook equivalent amounts of daily voluntary exercise in these conditions, but the timing of the wheel access altered the normal diurnal rhythms in heart rate and body temperature. For example, exercise scheduled late in the active period shifted the time of peak heart rate and body temperature to a later time of day. For a closer look at the cellular clocks within different tissues, the researchers measured circadian rhythms in vitro using a bioluminescent marker of a core clock protein, PER2. By observing the rhythms of PER2 expression the researchers could determine if exercise treatments altered key properties of the circadian system. They were surprised to find that exercise restricted to early in the active phase decreased the amplitude of the rhythm recorded from the circadian pacemaker, the suprachiasmatic nucleus. In contrast, at either time tested, scheduled exercise increased the amplitude of the rhythm recorded from another important clock in the network, the adrenal gland. Exercise also altered other key properties such as phase in adrenal and liver, and period in the suprachiasmatic nucleus, adrenal and heart. These studies suggested that exercise could be altering fundamental properties of circadian system components. Could scheduled exercise be used to fix a broken clock? In prior research, mice deficient in the peptide vasoactive intestinal polypeptide (VIP) have been shown to have disruptions to their circadian system regulating physiology and behaviour. Thus, it was not surprising that these researchers found the VIP-deficient mice showed reduced power in circadian rhythms of physiology and reduced amplitude of rhythms recorded in vitro. Interestingly, exercise, particularly when scheduled in the second half of the active period, was able to reestablish key properties of the rhythms and dramatically increased the amplitude of circadian rhythms recorded from the suprachiasmatic nuclei of these mice. Previous studies have also established that mice deficient in VIP show loss of synchrony among different cells in the suprachiasmatic nucleus (Aton et al. 2005). Mice lacking the receptor that VIP targets in the suprachiasmatic nucleus show reduced amplitude circadian rhythms measured from the suprachiasmatic tissue in vitro (Hughes et al. 2008). The current study supports those prior findings (as well as others that space limitations prevent citation here) and builds evidence for the VIP-deficient mouse as a promising model for the study of diminished circadian clock function. These studies in mice may help us to develop exercise-based treatments to strengthen the circadian system for populations such as ageing adults or rotating shift workers. Scheduled exercise has been shown to alter the timing of circadian rhythms in humans, even in older populations (Baehr et al. 2003). Future research will likely help us better understand the mechanism underlying these effects, and perhaps suggest a method of treatment for circadian disruption.