From Fast Oscillations to Circadian Rhythms: Coupling at Multiscale Frequency Bands in the Rodent Subcortical Visual System

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The subcortical visual system (SVS) is a unique collection of brain structures localised in the thalamus, hypothalamus and midbrain. The SVS receives ambient light inputs from retinal ganglion cells and integrates this signal with internal homeostatic demands to influence physiology. During this processing, a multitude of oscillatory frequency bands coalesces, with some originating from the retinas, while others are intrinsically generated in the SVS. Collectively, these rhythms are further modulated by the day and night cycle. The multiplexing of these diverse frequency bands (from circadian to infra-slow and gamma oscillations) makes the SVS an interesting system to study coupling at multiscale frequencies. We review the functional organisation of the SVS, and the various frequencies generated and processed by its neurons. We propose a perspective on how these different frequency bands couple with one another to synchronise the activity of the SVS to control physiology and behaviour.National Science CentreBiotechnology and Biological Sciences Research Council (BBSRC)Higher Education Sprout Project, Taiwan Ministry of EducationTaiwan Ministry of Science and TechnologyTaipei Medical Universit

Classification of image distortions in terms of Petrov types

An observer surrounded by sufficiently small spherical light sources at a fixed distance will see a pattern of elliptical images distributed over the sky, owing to the distortion effect (shearing effect) of the spacetime geometry upon light bundles. In lowest non-trivial order with respect to the distance, this pattern is completely determined by the conformal curvature tensor (Weyl tensor) at the observation event. In this paper we derive formulas that allow to calculate these distortion patterns in terms of the Newman-Penrose formalism. Then we represent the distortion patterns graphically for all Petrov types, and we discuss their dependence on the velocity of the observer.Comment: 22 pages, 8 eps-figures; revised version, parts of Introduction and Conclusions rewritte

Keeping time in the lamina terminalis: Novel oscillator properties of forebrain sensory circumventricular organs

Drinking behavior and osmotic regulatory mechanisms exhibit clear daily variation which is necessary for achieving the homeostatic osmolality. In mammals, the master clock in the brain's suprachiasmatic nuclei has long been held as the main driver of circadian (24 h) rhythms in physiology and behavior. However, rhythmic clock gene expression in other brain sites raises the possibility of local circadian control of neural activity and function. The subfornical organ (SFO) and the organum vasculosum laminae terminalis (OVLT) are two sensory circumventricular organs (sCVOs) that play key roles in the central control of thirst and water homeostasis, but the extent to which they are subject to intrinsic circadian control remains undefined. Using a combination of ex vivo bioluminescence and in vivo gene expression, we report for the first time that the SFO contains an unexpectedly robust autonomous clock with unusual spatiotemporal characteristics in core and noncore clock gene expression. Furthermore, putative single‐cell oscillators in the SFO and OVLT are strongly rhythmic and require action potential‐dependent communication to maintain synchrony. Our results reveal that these thirst‐controlling sCVOs possess intrinsic circadian timekeeping properties and raise the possibility that these contribute to daily regulation of drinking behavior

The ideal relativistic rotating gas as a perfect fluid with spin

We show that the ideal relativistic spinning gas at complete thermodynamical equilibrium is a fluid with a non-vanishing spin density tensor \sigma_\mu \nu. After having obtained the expression of the local spin-dependent phase space density f(x,p)_(\sigma \tau) in the Boltzmann approximation, we derive the spin density tensor and show that it is proportional to the acceleration tensor Omega_\mu \nu constructed with the Frenet-Serret tetrad. We recover the proper generalization of the fundamental thermodynamical relation, involving an additional term -(1/2) \Omega_\mu \nu \sigma^\mu \nu. We also show that the spin density tensor has a non-vanishing projection onto the four-velocity field, i.e. t^\mu= sigma_\mu \nu u^\nu \ne 0, in contrast to the common assumption t^\mu = 0, known as Frenkel condition, in the thus-far proposed theories of relativistic fluids with spin. We briefly address the viewpoint of the accelerated observer and inertial spin effects.Comment: Final published version in Annals of Physic

Principal null directions of perturbed black holes

The properties of principal null directions of a perturbed black hole are investigated. It shown that principal null directions are directly observable quantities characterizing the space-time. A definition of a perturbed space-time, generalizing that given by Stewart and Walker is proposed. This more general framework allows one to include descriptions of a given space-time other than by a pair $(M,g)$ where $M$ is a four-dimensional differential manifold and $g$ a Lorentz metric. Examples of alternative characterizations are the curvature representation of Karlhede and others, the Newman-Penrose representation or observable quantities involving principal null directions. The conditions are studied under which the various alternative choices of observables provide equivalent descriptions of the space-time.Comment: To appear in Class. Quantum Gra

Monocyte behaviour and tissue transglutaminase expression during experimental autoimmune encephalomyelitis in transgenic CX3CR1gfp/gfp mice

Leukocyte infiltration into the central nervous system (CNS) is a key pathological feature in multiple sclerosis (MS) and the MS animal model experimental autoimmune encephalomyelitis (EAE). Recently, preventing leukocyte influx into the CNS of MS patients is the main target of MS therapies and insight into cell behaviour in the circulation is needed for further elucidation of such therapies. In this study, we aimed at in vivo visualization of monocytes in a time-dependent manner during EAE. Using intravital two-photon microscopy (IVM), we imaged CX3CR1gfp/gfp mice during EAE, visualizing CX3CR1-GFP+ monocytes and their dynamics in the spinal cord vasculature. Our observations showed that intraluminal crawling of CX3CR1-GFP+ monocytes increased even before the clinical onset of EAE due to immunization of the animals. Furthermore, intraluminal crawling remained elevated during ongoing clinical disease. Besides, the displacement of these cells was larger during the peak of EAE compared to the control animals. In addition, we showed that the enzyme tissue transglutaminase (TG2), which is present in CNS-infiltrated cells in MS patients, is likewise found in CX3CR1-GFP+ monocytes in the spinal cord lesions and at the luminal side of the vasculature during EAE. It might thereby contribute to adhesion and crawling of monocytes, facilitating extravasation into the CNS. Thus, we put forward that interference with monocyte adhesion, by e.g. inhibition of TG2, should be applied at a very early stage of EAE and possibly MS, to effectively combat subsequent pathology

Proglucagon signalling in the rat dorsomedial hypothalamus - physiology and high-fat diet-mediated alterations

A relatively new pharmacological target in obesity treatment has been the preproglucagon (PPG) signalling, predominantly with glucagon-like peptide (GLP) 1 receptor agonists. As far as the PPG role within the digestive system is well recognised, its actions in the brain remain understudied. Here, we investigated PPG signalling in the Dorsomedial Hypothalamus (DMH), a structure involved in feeding regulation and metabolism, using in situ hybridisation, electrophysiology, and immunohistochemistry. Our experiments were performed on animals fed both control, and high-fat diet (HFD), uncovering HFD-mediated alterations. First, sensitivity to exendin-4 (Exn4, a GLP1R agonist) was shown to increase under HFD, with a higher number of responsive neurons. The amplitude of the response to both Exn4 and oxyntomodulin (Oxm) was also altered, diminishing its relationship with the cells' spontaneous firing rate. Not only neuronal sensitivity, but also GLP1 presence, and therefore possibly release, was influenced by HFD. Immunofluorescent labelling of the GLP1 showed changes in its density depending on the metabolic state (fasted/fed), but this effect was eliminated by HFD feeding. Interestingly, these dietary differences were absent after a period of restricted feeding, allowing for an anticipation of the alternating metabolic states, which suggests possible prevention of such outcome

High-fat-diet-evoked disruption of the rat dorsomedial hypothalamic clock can be prevented by restricted nighttime feeding

Obesity is a growing health problem for modern society; therefore, it has become extremely important to study not only its negative implications but also its developmental mechanism. Its links to disrupted circadian rhythmicity are indisputable but are still not well studied on the cellular level. Circadian food intake and metabolism are controlled by a set of brain structures referred to as the food-entrainable oscillator, among which the dorsomedial hypothalamus (DMH) seems to be especially heavily affected by diet-induced obesity. In this study, we evaluated the effects of a short-term high-fat diet (HFD) on the physiology of the male rat DMH, with special attention to its day/night changes. Using immunofluorescence and electrophysiology we found that both cFos immunoreactivity and electrical activity rhythms become disrupted after as few as 4 weeks of HFD consumption, so before the onset of excessive weight gain. This indicates that the DMH impairment is a possible factor in obesity development. The DMH cellular activity under an HFD became increased during the non-active daytime, which coincides with a disrupted rhythm in food intake. In order to explore the relationship between them, a separate group of rats underwent time-restricted feeding with access to food only during the nighttime. Such an approach completely abolished the disruptive effects of the HFD on the DMH clock, confirming its dependence on the feeding schedule of the animal. The presented data highlight the importance of a temporally regulated feeding pattern on the physiology of the hypothalamic center for food intake and metabolism regulation, and propose time-restricted feeding as a possible prevention of the circadian dysregulation observed under an HFD

Dysphagia in Intensive Care Evaluation (DICE): An International Cross-Sectional Survey.

Dysphagia occurs commonly in the intensive care unit (ICU). Despite the clinical relevance, there is little worldwide research on prevention, assessment, evaluation, and/or treatment of dysphagia for ICU patients. We aimed to gain insight into this international knowledge gap. We conducted a multi-center, international online cross-sectional survey of adult ICUs. Local survey distribution champions were recruited through professional and personal networks. The survey was administered from November 2017 to June 2019 with three emails and a final telephone reminder. Responses were received from 746 ICUs (26 countries). In patients intubated > 48 h, 17% expected a > 50% chance that dysphagia would develop. This proportion increased to 43% in patients intubated > 7 days, and to 52% in tracheotomized patients. Speech-language pathologist (SLP) consultation was available in 66% of ICUs, only 4% reported a dedicated SLP. Although 66% considered a routine post-extubation dysphagia protocol important, most (67%) did not have a protocol. Few ICUs routinely assessed for dysphagia after 48 h of intubation (30%) or tracheostomy (41%). A large proportion (46%) used water swallow screening tests to determine aspiration, few (8%) used instrumental assessments (i.e., flexible endoscopic evaluation of swallowing). Swallowing exercises were used for dysphagia management by 30% of ICUs. There seems to be limited awareness among ICU practitioners that patients are at risk of dysphagia, particularly as ventilation persists, protocols, routine assessment, and instrumental assessments are generally not used. We recommend the development of a research agenda to increase the quality of evidence and ameliorate the implementation of evidence-based dysphagia protocols by dedicated SLPs