The gut microbiota facilitate their host tolerance to extreme temperatures.

BACKGROUND: Exposure to extreme cold or heat temperature is one leading cause of weather-associated mortality and morbidity in animals. Emerging studies demonstrate that the microbiota residing in guts act as an integral factor required to modulate host tolerance to cold or heat exposure, but common and unique patterns of animal-temperature associations between cold and heat have not been simultaneously examined. Therefore, we attempted to investigate the roles of gut microbiota in modulating tolerance to cold or heat exposure in mice. RESULTS: The results showed that both cold and heat acutely change the body temperature of mice, but mice efficiently maintain their body temperature at conditions of chronic extreme temperatures. Mice adapt to extreme temperatures by adjusting body weight gain, food intake and energy harvest. Fascinatingly, 16 S rRNA sequencing shows that extreme temperatures result in a differential shift in the gut microbiota. Moreover, transplantation of the extreme-temperature microbiota is sufficient to enhance host tolerance to cold and heat, respectively. Metagenomic sequencing shows that the microbiota assists their hosts in resisting extreme temperatures through regulating the host insulin pathway. CONCLUSIONS: Our findings highlight that the microbiota is a key factor orchestrating the overall energy homeostasis under extreme temperatures, providing an insight into the interaction and coevolution of hosts and gut microbiota.

Threshold shifts and developmental temperature impact trade-offs between tolerance and plasticity.

Mounting evidence suggests that ectotherms are already living close to their upper physiological thermal limits. Phenotypic plasticity has been proposed to reduce the impact of climate change in the short-term providing time for adaptation, but the tolerance-plasticity trade-off hypothesis predicts organisms with higher tolerance have lower plasticity. Empirical evidence is mixed, which may be driven by methodological issues such as statistical artefacts, nonlinear reaction norms, threshold shifts or selection. Here, we examine whether threshold shifts (organisms with higher tolerance require stronger treatments to induce maximum plastic responses) influence tolerance-plasticity trade-offs in hardening capacity for desiccation tolerance and critical thermal maximum (CTMAX) across Drosophila species with varying distributions/sensitivity to desiccation/heat stress. We found evidence for threshold shifts in both traits; species with higher heat/desiccation tolerance required longer hardening treatments to induce maximum hardening responses. Species with higher heat tolerance also showed reductions in hardening capacity at higher developmental acclimation temperatures. Trade-off patterns differed depending on the hardening treatment used and the developmental temperature flies were exposed to. Based on these findings, studies that do not consider threshold shifts, or that estimate plasticity under a narrow set of environments, will have a limited ability to assess trade-off patterns and differences in plasticity across species/populations more broadly.

Differences in cardiac adaptation to exercise in male and female athletes assessed by noninvasive techniques: a state-of-the-art review.

Athlete's heart is generally regarded as a physiological adaptation to regular training, with specific morphological and functional alterations in the cardiovascular system. Development of the noninvasive imaging techniques over the past several years enabled better assessment of cardiac remodeling in athletes, which may eventually mimic certain pathological conditions with the potential for sudden cardiac death, or disease progression. The current literature provides a compelling overview of the available methods that target the interrelation of prolonged exercise with cardiac structure and function. However, this data stems from scientific studies that included mostly male athletes. Despite the growing participation of females in competitive sport meetings, little is known about the long-term cardiac effects of repetitive training in this population. There are several factors-biochemical, physiological and psychological, that determine sex-dependent cardiac response. Herein, the aim of this review was to compare cardiac adaptation to endurance exercise in male and female athletes with the use of electrocardiographic, echocardiographic, and biochemical examination, to determine the sex-specific phenotypes, and to improve the healthcare providers' awareness of cardiac remodeling in athletes. Finally, we discuss the possible exercise-induced alternations that should arouse suspicion of pathology and be further evaluated.

Functional EPAS1/HIF2A missense variant is associated with hematocrit in Andean highlanders.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.

Evaluating the impact of high-altitude training on athletic performance in andean athletes

Objective:The research aims to determine the impact of high-Altitude training on athletic performance in Andean athletes. Using the distinct physiological adaptations that people who live in high-altitude areas have evolved, this study examines the effects of high-altitude training on the athletic performance of Andean athletes. This study investigates Andean athletes' baseline physiological characteristics (red blood cell count, oxygen saturation, and lung capacity). An organizedhigh-altitude training programaims to evaluate the impact of altitude on strength, cardiovascular endurance, and overall athletic performance. Working with geneticists, the research explores genetic variables that affect Andean athletes' capacity to adjust to training at high altitudes. For measuring, the research used SPSS software and generated results including descriptive statistics, correlation coefficient, the model summary, and chi-square analysis between the independent and dependent. The purpose of the study is to record any negative effects that participants may have experienced as well as any potential benefits and difficulties related to purposeful high-altitude training. The results have the potential to improve training protocols, guide customizedstrategies based on genetic profiles, and advance the conversation on the moral ramifications of exceeding human potential in the sake of sports achievement. The overall result found a positive impact of high-altitude training on athletic performance in Andean athletes. This research aims to further our understanding of the intricate interactions between purposeful training, innate abilities, and athletic performance in demanding settings (AU)

Stronger tilt aftereffects in individuals diagnosed with schizophrenia spectrum disorders but not bipolar disorder.

An altered use of context and experience to interpret incoming information has been posited to explain schizophrenia symptoms. The visual system can serve as a model system for examining how context and experience guide perception and the neural mechanisms underlying putative alterations. The influence of prior experience on current perception is evident in visual aftereffects, the perception of the "opposite" of a previously viewed stimulus. Aftereffects are associated with neural adaptation and concomitant change in strength of lateral inhibitory connections in visually responsive neurons. In a previous study, we observed stronger aftereffects related to orientation (tilt aftereffects) but not luminance (negative afterimages) in individuals diagnosed with schizophrenia, which we interpreted as potentially suggesting altered cortical (but not subcortical) adaptability and local changes in excitatory-inhibitory interactions. Here, we tested whether stronger tilt aftereffects were specific to individuals with schizophrenia or extended to individuals with bipolar disorder. We measured tilt aftereffects and negative afterimages in 32 individuals with bipolar disorder, and compared aftereffect strength to a previously reported group of 36 individuals with schizophrenia and 22 healthy controls. We observed stronger tilt aftereffects, but not negative afterimages, in individuals with schizophrenia as compared to both controls and individuals with bipolar disorder, who did not differ from each other. These results mitigate concerns that stronger tilt aftereffects in schizophrenia are a consequence of medication or of the psychosocial consequences of a severe mental illness.

Behavioral plasticity during acute heat stress: heat hardening increases the expression of boldness.

Climate change is creating novel thermal environments via rising temperatures and increased frequency of severe weather events. Short-term phenotypic adjustments, i.e., phenotypic plasticity, may facilitate species persistence during adverse environmental conditions. A plastic response that increases thermal tolerance is heat hardening, which buffers organisms from extreme heat and may enhance short term survival. However, heat hardening responses may incur a cost with concomitant decreases in thermal preference and physiological performance. Thus, phenotypic shifts accompanying a hardening response may be maladaptive in warming climates. Understanding how heat hardening influences other traits associated with fitness and survival will clarify its potential as an adaptive response to altered thermal niches. Here, we studied the effects of heat hardening on boldness behavior in the color polymorphic tree lizard, Urosaurus ornatus. Boldness in lizards influences traits such as territory maintenance, mating success, and survivorship and is repeatable in U. ornatus. We found that when lizards underwent a heat hardening response, boldness expression significantly increased. This trend was driven by males. Bolder individuals also exhibited lower field active body temperatures. This behavioral response to heat hardening may increase resource holding potential and territoriality in stressful environments but may also increase predation risk. This study highlights the need to detail associated phenotypic shifts with stress responses to fully understand their adaptive potential in rapidly changing environments.

Sequential maturation of stimulus-specific adaptation in the mouse lemniscal auditory system.

Stimulus-specific adaptation (SSA), the reduction of neural activity to a common stimulus that does not generalize to other, rare stimuli, is an essential property of our brain. Although well characterized in adults, it is still unknown how it develops during adolescence and what neuronal circuits are involved. Using in vivo electrophysiology and optogenetics in the lemniscal pathway of the mouse auditory system, we observed SSA to be stable from postnatal day 20 (P20) in the inferior colliculus, to develop until P30 in the auditory thalamus and even later in the primary auditory cortex (A1). We found this maturation process to be experience-dependent in A1 but not in thalamus and to be related to alterations in deep but not input layers of A1. We also identified corticothalamic projections to be implicated in thalamic SSA development. Together, our results reveal different circuits underlying the sequential SSA maturation and provide a unique perspective to understand predictive coding and surprise across sensory systems.

Shifting focus: Time to look beyond the classic physiological adaptations associated with human heat acclimation.

Planet Earth is warming at an unprecedented rate and our future is now assured to be shaped by the consequences of more frequent hot days and extreme heat. Humans will need to adapt both behaviorally and physiologically to thrive in a hotter climate. From a physiological perspective, countless studies have shown that human heat acclimation increases thermoeffector output (i.e., sweating and skin blood flow) and lowers cardiovascular strain (i.e., heart rate) during heat stress. However, the mechanisms mediating these adaptations remain understudied. Furthermore, several possible benefits of heat acclimation for other systems and functions involved in maintaining health and performance during heat stress remain to be elucidated. This review summarizes recent advances in human heat acclimation, with emphasis on recent studies that (1) advanced our understanding of the mechanisms mediating improved thermoeffector output and (2) investigated adaptations that go beyond those classically associated with heat acclimation. We highlight that these studies have contributed to a better understanding of the integrated physiological responses underlying human heat acclimation while leaving key unanswered questions that will need to be addressed in the future.

Short-term learning of the vestibulo-ocular reflex induced by a custom interactive computer game.

Retinal image slip during head rotation drives motor learning in the rotational vestibulo-ocular reflex (VOR) and forms the basis of gaze-stability exercises that treat vestibular dysfunction. Clinical exercises, however, are unengaging, cannot easily be titrated to the level of impairment, and provide neither direct feedback nor tracking of the patient's adherence, performance, and progress. To address this, we have developed a custom application for VOR training based on an interactive computer game. In this study, we tested the ability of this game to induce VOR learning in individuals with normal vestibular function, and we compared the efficacy of single-step and incremental learning protocols. Eighteen participants played the game twice on different days. All participants tolerated the game and were able to complete both sessions. The game scenario incorporated a series of brief head rotations, similar to active head impulses, that were paired with a dynamic acuity task and with a visual-vestibular mismatch (VVM) intended to increase VOR gain (single-step: 300 successful trials at ×1.5 viewing; incremental: 100 trials each of ×1.13, ×1.33, and ×1.5 viewing). Overall, VOR gain increased by 15 ± 4.7% (mean ± 95% CI, P < 0.001). Gains increased similarly for active and passive head rotations, and, contrary to our hypothesis, there was little effect of the learning strategy. This study shows that an interactive computer game provides robust VOR training and has the potential to deliver effective, engaging, and trackable gaze-stability exercises to patients with a range of vestibular dysfunctions.NEW & NOTEWORTHY This study demonstrates the feasibility and efficacy of a customized computer game to induce motor learning in the high-frequency rotational vestibulo-ocular reflex. It provides a physiological basis for the deployment of this technology to clinical vestibular rehabilitation.

Facilitated adaptation via structural learning increases bimanual interference.

Bimanual coordination is an essential feature of the motor system, yet interactions between the limbs during independent control remain poorly understood. Interference between the two hands, or the assimilation of movement characteristics between the two effectors, can be induced by perturbing one arm (e.g., via visuomotor rotation) and then measuring the effects in the contralateral limb. In this study, we sought to further determine the role adaptation plays in bimanual interference using a structural learning paradigm to alter feedback regulation in reaching. We trained healthy participants to counter 60 unique random rotations in right hand visual feedback over 240 reaches. Following this, we assessed feedforward and feedback measures of interference in a bimanual reaching task where the right hand was exposed to a fixed visual feedback rotation while the left hand reached without visual feedback. We found that participants who had been exposed to the structural training task in the right hand showed increased left hand interference during the first 20 trials of the test task. Moreover, interference was greater in feedback, rather than feedforward control parameters. The results further suggest that structural learning enhances bimanual interference via sensory feedback upregulation.

Cortical bone adaptation response is region specific, but not peak load dependent: insights from µ CT image analysis and mechanostat simulations of the mouse tibia loading model.

The two major aims of the present study were: (i) quantify localised cortical bone adaptation at the surface level using contralateral endpoint imaging data and image analysis techniques, and (ii) investigate whether cortical bone adaptation responses are universal or region specific and dependent on the respective peak load. For this purpose, we re-analyse previously published µ CT data of the mouse tibia loading model that investigated bone adaptation in response to sciatic neurectomy and various peak load magnitudes (F = 0, 2, 4, 6, 8, 10, 12 N). A beam theory-based approach was developed to simulate cortical bone adaptation in different sections of the tibia, using longitudinal strains as the adaptive stimuli. We developed four mechanostat models: universal, surface-based, strain directional-based, and combined surface and strain direction-based. Rates of bone adaptation in these mechanostat models were computed using an optimisation procedure (131,606 total simulations), performed on a single load case (F = 10 N). Subsequently, the models were validated against the remaining six peak loads. Our findings indicate that local bone adaptation responses are quasi-linear and bone region specific. The mechanostat model which accounted for differences in endosteal and periosteal regions and strain directions (i.e. tensile versus compressive) produced the lowest root mean squared error between simulated and experimental data for all loads, with a combined prediction accuracy of 76.6, 55.0 and 80.7% for periosteal, endosteal, and cortical thickness measurements (in the midshaft of the tibia). The largest root mean squared errors were observed in the transitional loads, i.e. F = 2 to 6 N, where inter-animal variability was highest. Finally, while endpoint imaging studies provide great insights into organ level bone adaptation responses, the between animal and loaded versus control limb variability make simulations of local surface-based adaptation responses challenging.

Effects of prism adaptation and visual scanning training on perceptual and response bias in unilateral spatial neglect.

In some patients with unilateral spatial neglect, symptoms reflect impaired lateralized spatial attention and representation (perceptual bias) whereas in others the inability to respond to stimuli located in contralesional space (response bias). Here, we investigated whether prismatic adaptation (PA) and visual scanning training (VST) differentially affect perceptual and response bias and whether rehabilitation outcome depends on the type of bias underlying symptoms. Two groups of neglect patients in the subacute phase were evaluated before, immediately after, and two weeks following 10 days of PA (n = 9) or VST (n = 9). Standard neuropsychological tests (i.e., Behavioural Inattentional Test, Diller cancellation test, and Line Bisection test) were administered to assess neglect symptoms, while the Landmark task was used to disentangle perceptual and response biases. Performance on the Landmark task revealed that PA was more effective in improving the perceptual bias, while VST mainly modulated the response bias. Neuropsychological tests performance suggested that VST is better suited to modulate neglect in patients with response bias, while PA may be effective in patients with both types of bias. These findings may offer novel insights into the efficacy of PA and VST in the rehabilitation of perceptual and response biases in patients with neglect.

Geography and developmental plasticity shape post-larval thermal tolerance in the golden star tunicate, Botryllus schlosseri.

Local adaptation and phenotypic plasticity play key roles in mediating organisms' ability to respond to spatiotemporal variation in temperature. These two processes often act together to generate latitudinal or elevational clines in acute temperature tolerance. Phenotypic plasticity is also subject to local adaptation, with the expectation that populations inhabiting more variable environments should exhibit greater phenotypic plasticity of thermal tolerance. Here we examine the potential for local adaptation and developmental plasticity of thermal tolerance in the widespread invasive tunicate Botryllus schlosseri. By comparing five populations across a thermal gradient spanning 4.4° of latitude in the northwest Atlantic, we demonstrate that warmer populations south of the Gulf of Maine exhibit significantly increased (∼0.2 °C) post-larval temperature tolerance relative to the colder populations within it. We also show that B. schlosseri post-larvae possess a high degree of developmental plasticity for this trait, shifting their median temperature of survival (LT50) upwards by as much as 0.18 °C per 1 °C increase in environmental temperature. Lastly, we found that populations vary in their degrees of developmental plasticity, with populations that experience more pronounced short-term temperature variability exhibiting greater developmental plasticity, suggesting the local adaptation of developmental plasticity. By comparing the thermal tolerance of populations across space and through time, we demonstrate how geography and developmental plasticity have shaped thermal tolerance in B. schlosseri. These results help inform our understanding of how species are able to adjust their thermal physiology in new environments, including those encountered during invasion and under increasingly novel climate conditions.

Translating In Vitro Models of Exercise in Human Muscle Cells: A Mitocentric View.

Human skeletal muscle cell (HSkMC) models provide the opportunity to examine in vivo training-induced muscle-specific mitochondrial adaptations, additionally allowing for deeper interrogation into the effect of in vitro exercise models on myocellular mitochondrial quality and quantity. As such, this review will compare and contrast the effects of in vivo and in vitro models of exercise on mitochondrial adaptations in HSkMCs.

Divisively normalized neuronal processing of uncertain visual feedback for visuomotor learning.

When encountering a visual error during a reaching movement, the motor system improves the motor command for the subsequent trial. This improvement is impaired by visual error uncertainty, which is considered evidence that the motor system optimally estimates the error. However, how such statistical computation is accomplished remains unclear. Here, we propose an alternative scheme implemented with a divisive normalization (DN): the responses of neuronal elements are normalized by the summed activity of the population. This scheme assumes that when an uncertain visual error is provided by multiple cursors, the motor system processes the error conveyed by each cursor and integrates the information using DN. The DN model reproduced the patterns of learning response to 1-3 cursor errors and the impairment of learning response with visual error uncertainty. This study provides a new perspective on how the motor system updates motor commands according to uncertain visual error information.

A power law describes the magnitude of adaptation in neural populations of primary visual cortex.

How do neural populations adapt to the time-varying statistics of sensory input? We used two-photon imaging to measure the activity of neurons in mouse primary visual cortex adapted to different sensory environments, each defined by a distinct probability distribution over a stimulus set. We find that two properties of adaptation capture how the population response to a given stimulus, viewed as a vector, changes across environments. First, the ratio between the response magnitudes is a power law of the ratio between the stimulus probabilities. Second, the response direction to a stimulus is largely invariant. These rules could be used to predict how cortical populations adapt to novel, sensory environments. Finally, we show how the power law enables the cortex to preferentially signal unexpected stimuli and to adjust the metabolic cost of its sensory representation to the entropy of the environment.

Reduced corticospinal drive and inflexible temporal adaptation during visually guided walking in older adults.

Corticospinal drive during walking is reduced in older adults compared with young adults, but it is not clear how this decrease might compromise one's ability to adjust stepping, particularly during visuomotor adaptation. We hypothesize that age-related changes in corticospinal drive could predict differences in older adults' step length and step time adjustments in response to visual perturbations compared with younger adults. Healthy young (n = 21; age 18-33 yr) and older adults (n = 20; age 68-80 yr) were tested with a treadmill task, incorporating visual feedback of the foot position and stepping targets in real-time. During adaptation, the visuomotor gain was reduced on one side, causing the foot cursor and step targets to move slower on that side of the screen (i.e., split-visuomotor adaptation). Corticospinal drive was quantified by coherence between electromyographic signals in the beta-gamma frequency band (15-45 Hz). The results showed that 1) older adults adapted to visuomotor perturbations during walking, with a similar reduction in error asymmetry compared with younger adults; 2) however, older adults showed reduced adaptation in step time symmetry, despite demonstrating similar adaptation in step length asymmetry compared with younger adults; and 3) smaller overall changes in step time asymmetry was associated with reduced corticospinal drive to the tibialis anterior in the slow leg during split-visuomotor adaptation. These findings suggest that changes in corticospinal drive may affect older adults' control of step timing in response to visual challenges. This could be important for safe navigation when walking in different environments or dealing with unexpected circumstances.NEW & NOTEWORTHY Corticospinal input is essential for visually guided walking, especially when the walking pattern must be modified to accurately step on safe locations. Age-related changes in corticospinal drive are associated with inflexible step time, which necessitates different locomotor adaptation strategies in older adults.

Conceptual foundations of physiological regulation incorporating the free energy principle and self-organized criticality.

Bettinger, J. S., K. J. Friston. Conceptual Foundations of Physiological Regulation incorporating the Free Energy Principle & Self-Organized Criticality. NEUROSCI BIOBEHAV REV 23(x) 144-XXX, 2022. Since the late nineteen-nineties, the concept of homeostasis has been contextualized within a broader class of "allostatic" dynamics characterized by a wider-berth of causal factors including social, psychological and environmental entailments; the fundamental nature of integrated brain-body dynamics; plus the role of anticipatory, top-down constraints supplied by intrinsic regulatory models. Many of these evidentiary factors are integral in original descriptions of homeostasis; subsequently integrated; and/or cite more-general operating principles of self-organization. As a result, the concept of allostasis may be generalized to a larger category of variational systems in biology, engineering and physics in terms of advances in complex systems, statistical mechanics and dynamics involving heterogenous (hierarchical/heterarchical, modular) systems like brain-networks and the internal milieu. This paper offers a three-part treatment. 1) interpret "allostasis" to emphasize a variational and relational foundation of physiological stability; 2) adapt the role of allostasis as "stability through change" to include a "return to stability" and 3) reframe the model of homeostasis with a conceptual model of criticality that licenses the upgrade to variational dynamics.