Rhythmic Oscillations Research Articles

Global and local reduced models for interacting, heterogeneous agents.

Large collections of coupled, heterogeneous agents can manifest complex dynamical behavior presenting difficulties for simulation and analysis. However, if the collective dynamics lie on a low-dimensional manifold, then the original agent-based model may be approximated with a simplified surrogate model on and near the low-dimensional space where the dynamics live. Analytically identifying such simplified models can be challenging or impossible, but here we present a data-driven coarse-graining methodology for discovering such reduced models. We consider two types of reduced models: globally based models that use global information and predict dynamics using information from the whole ensemble and locally based models that use local information, that is, information from just a subset of agents close (close in heterogeneity space, not physical space) to an agent, to predict the dynamics of an agent. For both approaches, we are able to learn laws governing the behavior of the reduced system on the low-dimensional manifold directly from time series of states from the agent-based system. These laws take the form of either a system of ordinary differential equations (ODEs), for the globally based approach, or a partial differential equation (PDE) in the locally based case. For each technique, we employ a specialized artificial neural network integrator that has been templated on an Euler time stepper (i.e., a ResNet) to learn the laws of the reduced model. As part of our methodology, we utilize the proper orthogonal decomposition (POD) to identify the low-dimensional space of the dynamics. Our globally based technique uses the resulting POD basis to define a set of coordinates for the agent states in this space and then seeks to learn the time evolution of these coordinates as a system of ODEs. For the locally based technique, we propose a methodology for learning a partial differential equation representation of the agents; the PDE law depends on the state variables and partial derivatives of the state variables with respect to model heterogeneities. We require that the state variables are smooth with respect to model heterogeneities, which permit us to cast the discrete agent-based problem as a continuous one in heterogeneity space. The agents in such a representation bear similarity to the discretization points used in typical finite element/volume methods. As an illustration of the efficacy of our techniques, we consider a simplified coupled neuron model for rhythmic oscillations in the pre-Bötzinger complex and demonstrate how our data-driven surrogate models are able to produce dynamics comparable to the dynamics of the full system. A nontrivial conclusion is that the dynamics can be equally well reproduced by an all-to-all coupled and by a locally coupled model of the same agents.

No benefit of auditory closed-loop stimulation on memory for semantically-incongruent associations

Auditory closed-loop stimulation has gained traction in recent years as a means of enhancing slow oscillatory activity and, consequently, sleep-associated memory consolidation. Previous studies on this topic have primarily focused on the consolidation of semantically-congruent associations. In this study, we investigated the effect of auditory closed-loop stimulation on the overnight retention of semantically-incongruent associations. Twelve healthy males (age: M = 20.06, SD = 2.02 years) participated in two experimental conditions (simulation and sham). In the stimulation condition, clicks were delivered in phase with slow oscillation up-states, whereas in the sham condition no auditory stimuli were applied. Corroborating earlier work, stimulation (vs. sham) enhanced the slow oscillation rhythm, phase-coupled spindle activity and slow oscillation power. However, there was no benefit of stimulation on overnight memory retention. These findings suggest that closed-loop stimulation does not benefit semantically-incongruent associations.

Chronodisruption by chronic jetlag impacts metabolic and gastrointestinal homeostasis in male mice.

Chronodisruption desynchronizes peripheral clocks and leads to metabolic diseases. Feeding cues are important synchronizers of peripheral clocks and influence rhythmic oscillations in intestinal microbiota and their metabolites. We investigated whether chronic jetlag, mimicking frequent time zone travelling, affected the diurnal fluctuations in faecal short-chain fatty acid (SCFA) levels, that feed back to the gut clock to regulate rhythmicity in gut function. Rhythms in faecal SCFAs levels and in the expression of clock genes and epithelial markers were measured in the colonic mucosa of control and jetlagged mice. The entraining effect of SCFAs on the rhythm in clock gene mRNA expression was studied in primary colonic crypts. The role of the circadian clock in epithelial marker expression was studied in Arntl-/- mice. Chronic jetlag increased body weight gain and abolished the day/night food intake pattern which resulted in a phase-delay in the rhythm of faecal SCFAs that paralleled the shift in the expression of mucosal clock genes. This effect was mimicked by stimulation of primary colonic crypts from control mice with SCFAs. Jetlag abolished the rhythm in Tnfα, proglucagon and ghrelin expression but not in the expression of tight junction markers. Only a dampening in plasma glucagon-like peptide-1 but not in ghrelin levels was observed. Rhythms in ghrelin but not proglucagon mRNA expression were abolished in Arntl-/- mice. The altered food intake pattern during chronodisruption corresponds with the changes in rhythmicity of SCFA levels that entrain clock genes to affect rhythms in mRNA expression of gut epithelial markers.

A549 in-silico 1.0: A first computational model to simulate cell cycle dependent ion current modulation in the human lung adenocarcinoma.

Lung cancer is still a leading cause of death worldwide. In recent years, knowledge has been obtained of the mechanisms modulating ion channel kinetics and thus of cell bioelectric properties, which is promising for oncological biomarkers and targets. The complex interplay of channel expression and its consequences on malignant processes, however, is still insufficiently understood. We here introduce the first approach of an in-silico whole-cell ion current model of a cancer cell, in particular of the A549 human lung adenocarcinoma, including the main functionally expressed ion channels in the plasma membrane as so far known. This hidden Markov-based model represents the electrophysiology behind proliferation of the A549 cell, describing its rhythmic oscillation of the membrane potential able to trigger the transition between cell cycle phases, and it predicts membrane potential changes over the cell cycle provoked by targeted ion channel modulation. This first A549 in-silico cell model opens up a deeper insight and understanding of possible ion channel interactions in tumor development and progression, and is a valuable tool for simulating altered ion channel function in lung cancer electrophysiology.

Locomotor activity and resting local field potential oscillatory rhythms of 6-OHDA mouse model of Parkinson’s disease in response to acute and repeated treatments with L-dopa

Phase-amplitude coupling (PAC) of local field potential (LFP) has been recognized as higher-order representation of brain states. Neuronal loss in the striatum leads to Parkinson’s disease (PD) symptoms and modifies LFP oscillation. However, PAC in the striatum of PD mouse model induced by 6-hydroxydopamne (6-OHDA) remained to be investigated. Male Swiss albino ICR mice were implanted with intracranial electrode and injected with 6-OHDA to the left striatum. Levodopa (L-dopa) (10 mg/kg, oral) was used for treatment once a day from day 15–19. Locomotor activity and resting LFP signals were selectively analyzed on day 15 and 19. One-way ANOVA revealed significant decreases in travelled distance induced by 6-OHDA on both days (p ≤ 0.05). However, the decreased travelled distances were significantly reversed by L-dopa. On day 15, LFP powers of theta, alpha, beta and low gamma waves were significantly increased by 6-OHDA injection and the powers of beta and low gamma were significantly reversed to control level by treatment with L-dopa. On day 19, LFP powers of delta, theta, alpha, beta and low gamma waves were significantly increased by 6-OHDA injection and the powers of low gamma were significantly reversed to control level by treatment with L-dopa. Theta-gamma PAC analyses also confirmed significant increase in modulation index (MI) induced by 6-OHDA on day 19. However, L-dopa failed to significantly reverse the MI to control level. These findings indicated theta-gamma coupling in the striatum of PD mouse model. Taken together, change in striatal theta-gamma PAC might be one of biomarkers in addition to hypokinesia and increased LFP powers that reflect disrupted neural mechanisms in PD mouse model.

Predictive visuo-motor communication through neural oscillations

SummaryThe mechanisms coordinating action and perception over time are poorly understood. The sensory cortex needs to prepare for upcoming changes contingent on action, and this requires temporally precise communication that takes into account the variable delays between sensory and motor processing. Several theorists1,2 have proposed synchronization of the endogenous oscillatory activity observed in most regions of the brain3 as the basis for an efficient and flexible communication protocol between distal brain areas,2,4 a concept known as “communication through coherence.” Synchronization of endogenous oscillations5,6 occurs after a salient sensory stimulus, such as a flash or a sound,7, 8, 9, 10, 11 and after a voluntary action,12, 13, 14, 15, 16, 17, 18 and this directly impacts perception, causing performance to oscillate rhythmically over time. Here we introduce a novel fMRI paradigm to probe the neural sources of oscillations, based on the concept of perturbative signals, which overcomes the low temporal resolution of BOLD signals. The assumption is that a synchronized endogenous rhythm will modulate cortical excitability rhythmically, which should be reflected in the BOLD responses to brief stimuli presented at different phases of the oscillation cycle. We record rhythmic oscillations of V1 BOLD synchronized by a simple voluntary action, in phase with behaviorally measured oscillations in visual sensitivity in the theta range. The functional connectivity between V1 and M1 also oscillates at the same rhythm. By demonstrating oscillatory temporal coupling between primary motor and sensory cortices, our results strongly implicate communication through coherence to achieve precise coordination and to encode sensory-motor timing.

In Vivo Microelectrode Arrays for Detecting Multi-Region Epileptic Activities in the Hippocampus in the Latent Period of Rat Model of Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is a form of refractory focal epilepsy, which includes a latent period and a chronic period. Microelectrode arrays capable of multi-region detection of neural activities are important for accurately identifying the epileptic focus and pathogenesis mechanism in the latent period of TLE. Here, we fabricated multi-shank MEAs to detect neural activities in the DG, hilus, CA3, and CA1 in the TLE rat model. In the latent period in TLE rats, seizures were induced and changes in neural activities were detected. The results showed that induced seizures spread from the hilus and CA3 to other areas. Furthermore, interneurons in the hilus and CA3 were more excited than principal cells and exhibited rhythmic oscillations at approximately 15 Hz in grand mal seizures. In addition, the power spectral density (PSD) of neural spikes and local field potentials (LFPs) were synchronized in the frequency domain of the alpha band (9–15 Hz) after the induction of seizures. The results suggest that fabricated MEAs have the advantages of simultaneous and precise detection of neural activities in multiple subregions of the hippocampus. Our MEAs promote the study of cellular mechanisms of TLE during the latent period, which provides an important basis for the diagnosis of the lesion focus of TLE.

Consolidation of memory traces in cultured cortical networks requires low cholinergic tone, synchronized activity and high network excitability

In systems consolidation, encoded memories are replayed by the hippocampus during slow-wave sleep (SWS), and permanently stored in the neocortex. Declarative memory consolidation is believed to benefit from the oscillatory rhythms and low cholinergic tone observed in this sleep stage, but underlying mechanisms remain unclear. To clarify the role of cholinergic modulation and synchronized activity in memory consolidation, we applied repeated electrical stimulation in mature cultures of dissociated rat cortical neurons with high or low cholinergic tone, mimicking the cue replay observed during systems consolidation under distinct cholinergic concentrations. In the absence of cholinergic input, these cultures display activity patterns hallmarked by network bursts, synchronized events reminiscent of the low frequency oscillations observed during SWS. They display stable activity and connectivity, which mutually interact and achieve an equilibrium. Electrical stimulation reforms the equilibrium to include the stimulus response, a phenomenon interpreted as memory trace formation. Without cholinergic input, activity was burst-dominated. First application of a stimulus induced significant connectivity changes, while subsequent repetition no longer affected connectivity. Presenting a second stimulus at a different electrode had the same effect, whereas returning to the initial stimuli did not induce further connectivity alterations, indicating that the second stimulus did not erase the ‘memory trace’ of the first. Distinctively, cultures with high cholinergic tone displayed reduced network excitability and dispersed firing, and electrical stimulation did not induce significant connectivity changes. We conclude that low cholinergic tone facilitates memory formation and consolidation, possibly through enhanced network excitability. Network bursts or SWS oscillations may merely reflect high network excitability.

The Roles of Calmodulin and CaMKII in Cx36 Plasticity.

Anatomical and electrophysiological evidence that gap junctions and electrical coupling occur between neurons was initially confined to invertebrates and nonmammals and was thought to be a primitive form of synaptic transmission. More recent studies revealed that electrical communication is common in the mammalian central nervous system (CNS), often coexisting with chemical synaptic transmission. The subsequent progress indicated that electrical synapses formed by the gap junction protein connexin-36 (Cx36) and its paralogs in nonmammals constitute vital elements in mammalian and fish synaptic circuitry. They govern the collective activity of ensembles of coupled neurons, and Cx36 gap junctions endow them with enormous adaptive plasticity, like that seen at chemical synapses. Moreover, they orchestrate the synchronized neuronal network activity and rhythmic oscillations that underlie the fundamental integrative processes, such as memory and learning. Here, we review the available mechanistic evidence and models that argue for the essential roles of calcium, calmodulin, and the Ca2+/calmodulin-dependent protein kinase II in integrating calcium signals to modulate the strength of electrical synapses through interactions with the gap junction protein Cx36.

Interbeat interval variability versus frequency modulation of heart rate.

The heart rate in humans is regulated by the autonomic nervous system, which modulates the frequency of heart contractions, resulting in heart rate variability (HRV). Therefore, to assess the activity of the autonomic nervous system, which contains important information for medical diagnostics, methods based on the analysis of interbeat interval variability are often used. This approach does not require the use of invasive methods for measuring the signals of the autonomic nervous system, but its accuracy is an open question. Using mathematical modeling, we investigate the possibility of extracting the signal of frequency modulation of the heartbeats from the electrocardiogram (ECG) signal and conduct a detailed comparison of the extracted signal with the real modulating signal. Since the quality of extraction of the signal of frequency modulation from the ECG depends on the method of demodulation, we compare two different approaches. One is based on the detection of the main oscillation rhythm and its bandpass filtering, and the other on the heterodyning technique. It is shown that low-frequency (LF) and high-frequency (HF) oscillations in HRV associated, respectively, with sympathetic and parasympathetic modulation by the autonomic nervous system, in the general case, significantly differ from the signals of frequency modulation of the heart rate in shape, but have close similarity with them in the frequency domain. We find that in model systems, the similarity of the LF component of HRV with sympathetic modulation of the heart rate is higher than the similarity of the HF component of HRV with parasympathetic modulation.

Issue Cover (April 2021)

Journal of NeurochemistryVolume 157, Issue 1 Issue CoverFree Access Issue Cover (April 2021) First published: 05 April 2021 https://doi.org/10.1111/jnc.15058 Read the full article: ‘How to time the time -A preface to the special issue Circadian Rhythms in the Brain’ by J. H. Stehle, A. Zemmar, L. Hausmann (J. Neurochem. 2021, vol. 157 (1), pp. 6–10) on doi:10.1111/jnc.15311 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Front cover: In vitro visualization of endogenous rhythmic oscillation in the mouse suprachiasmatic nucleus (SCN) with a circadian (circa: about; dies: day) phase length. Image Content: Shown are six selected images taken from an explanted coronal brain slice from a transgenic PER1-luciferase transgenic mouse, containing the region of the hypothalamic suprachiasmatic nucleus (SCN). Pictures were taken at indicated circadian times (CT), with CT0 corresponding to ‘lights on’ and CT12 corresponding to ‘lights off’ for the animal prior to tissue preparation. SCN slices were cultured in complete darkness with the medium containing luciferin. Pictures were extracted from a video, with images sampled in 10 minutes time bins. Note the increasing bioluminescence with in vitro progressing CT, peaking during subjective mid-day. The visualization shows the paired structure of the mouse SCN, separated by the third ventricle and located directly dorsal of the optic chiasm (A. Jilg and J.H. Stehle, unpublished). Read the full article ‘How to time the time -A preface to the special issue Circadian Rhythms in the Brain’ by J. H. Stehle, A. Zemmar, L. Hausmann (J. Neurochem. 2021, vol. 157 (1), pp. 6–10) on doi:10.1111/jnc.15311 Volume157, Issue1Special Issue: Circadian Rhythms in the BrainApril 2021 RelatedInformation

Mecamylamine inhibits seizure-like activity in CA1-CA3 hippocampus through antagonism to nicotinic receptors.

Cholinergic modulation of hippocampal network function is implicated in multiple behavioral and cognitive states. Activation of nicotinic and muscarinic acetylcholine receptors affects neuronal excitability, synaptic transmission and rhythmic oscillations in the hippocampus. In this work, we studied the ability of the cholinergic system to sustain hippocampal epileptiform activity independently from glutamate and GABA transmission. Simultaneous CA3 and CA1 field potential recordings were obtained during the perfusion of hippocampal slices with the aCSF containing AMPA, NMDA and GABA receptor antagonists. Under these conditions, spontaneous epileptiform discharges synchronous between CA3 and CA1 were recorded. Epileptiform discharges were blocked by addition of the calcium-channel blocker Cd2+ and disappeared in CA1 after a surgical cut between CA3 and CA1. Cholinergic antagonist mecamylamine abolished CA3-CA1 synchronous epileptiform discharges, while antagonists of α7 and α4β2 nAChRs, MLA and DhβE, had no effect. Our results suggest that activation of nicotinic acetylcholine receptors can sustain CA3-CA1 synchronous epileptiform activity independently from AMPA, NMDA and GABA transmission. In addition, mecamylamine, but not α7 and α4β2 nAChRs antagonists, reduced bicuculline-induced seizure-like activity. The ability of mecamylamine to decrease hippocampal network synchronization might be associated with its therapeutic effects in a wide variety of CNS disorders including addiction, depression and anxiety.

Hypoxic Conditions Promote Rhythmic Contractile Oscillations Mediated by Voltage-Gated Sodium Channels Activation in Human Arteries.

Arterial smooth muscle exhibits rhythmic oscillatory contractions called vasomotion and believed to be a protective mechanism against tissue hypoperfusion or hypoxia. Oscillations of vascular tone depend on voltage and follow oscillations of the membrane potential. Voltage-gated sodium channels (Nav), responsible for the initiation and propagation of action potentials in excitable cells, have also been evidenced both in animal and human vascular smooth muscle cells (SMCs). For example, they contribute to arterial contraction in rats, but their physiopathological relevance has not been established in human vessels. In the present study, we investigated the functional role of Nav in the human artery. Experiments were performed on human uterine arteries obtained after hysterectomy and on SMCs dissociated from these arteries. In SMCs, we recorded a tetrodotoxin (TTX)-sensitive and fast inactivating voltage-dependent INa current. Various Nav genes, encoding α-subunit isoforms sensitive (Nav 1.2; 1.3; 1.7) and resistant (Nav 1.5) to TTX, were detected both in arterial tissue and in SMCs. Nav channels immunostaining showed uniform distribution in SMCs and endothelial cells. On arterial tissue, we recorded variations of isometric tension, ex vivo, in response to various agonists and antagonists. In arterial rings placed under hypoxic conditions, the depolarizing agent KCl and veratridine, a specific Nav channels agonist, both induced a sustained contraction overlaid with rhythmic oscillations of tension. After suppression of sympathetic control either by blocking the release of catecholamine or by antagonizing the target adrenergic response, rhythmic activity persisted while the sustained contraction was abolished. This rhythmic activity of the arteries was suppressed by TTX but, in contrast, only attenuated by antagonists of calcium channels, Na+/Ca2+ exchanger, Na+/K+-ATPase and the cardiac Nav channel. These results highlight the role of Nav as a novel key element in the vasomotion of human arteries. Hypoxia promotes activation of Nav channels involved in the initiation of rhythmic oscillatory contractile activity.

High-Frequency Visual Stimulation Primes Gamma Oscillations for Visually Evoked Phase Reset and Enhances Spatial Acuity.

The temporal frequency of sensory stimulation is a decisive factor in the plasticity of perceptual detection thresholds. However, surprisingly little is known about how distinct temporal parameters of sensory input differentially recruit activity of neuronal circuits in sensory cortices. Here we demonstrate that brief repetitive visual stimulation induces long-term plasticity of visual responses revealed 24 h after stimulation and that the location and generalization of visual response plasticity is determined by the temporal frequency of the visual stimulation. Brief repetitive low-frequency stimulation (2 Hz) is sufficient to induce a visual response potentiation that is expressed exclusively in visual cortex layer 4 and in response to a familiar stimulus. In contrast, brief, repetitive high-frequency stimulation (HFS, 20 Hz) is sufficient to induce a visual response potentiation that is expressed in all cortical layers and transfers to novel stimuli. HFS induces a long-term suppression of the activity of fast-spiking interneurons and primes ongoing gamma oscillatory rhythms for phase reset by subsequent visual stimulation. This novel form of generalized visual response enhancement induced by HFS is paralleled by an increase in visual acuity, measured as improved performance in a visual detection task.

Online and offline effects of transcranial alternating current stimulation of the primary motor cortex

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that allows interaction with endogenous cortical oscillatory rhythms by means of external sinusoidal potentials. The physiological mechanisms underlying tACS effects are still under debate. Whereas online (e.g., ongoing) tACS over the motor cortex induces robust state-, phase- and frequency-dependent effects on cortical excitability, the offline effects (i.e. after-effects) of tACS are less clear. Here, we explored online and offline effects of tACS in two single-blind, sham-controlled experiments. In both experiments we used neuronavigated transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) as a probe to index changes of cortical excitability and delivered M1 tACS at 10 Hz (alpha), 20 Hz (beta) and sham (30 s of low-frequency transcranial random noise stimulation; tRNS). Corticospinal excitability was measured by single pulse TMS-induced motor evoked potentials (MEPs). tACS was delivered online in Experiment 1 and offline in Experiment 2. In Experiment 1, the increase of MEPs size was maximal with the 20 Hz stimulation, however in Experiment 2 neither the 10 Hz nor the 20 Hz stimulation induced tACS offline effects. These findings support the idea that tACS affects cortical excitability only during online application, at least when delivered on the scalp overlying M1, thereby contributing to the development of effective protocols that can be applied to clinical populations.

Exogenous melatonin improves growth in hulless barley seedlings under cold stress by influencing the expression rhythms of circadian clock genes.

BackgroundMelatonin is a hormone substance that exists in various living organisms. Since it was discovered in the pineal gland of cattle in 1956, the function of melatonin in animals has been roughly clarified. Nevertheless, in plants, the research on melatonin is still insufficient. Hulless barley (Hordeum vulgare L. var. nudum hook. f.) is a crop that originates from cultivated barley in the east, usually grown on the Qinghai-Tibet Plateau, becoming the most important food crop in this area. Although the genome and transcriptome research of highland barley has gradually increased recently years, there are still many problems about how hulless barley adapts to the cold climate of the Qinghai-Tibet Plateau.MethodsIn this study, we set three temperature conditions 25°C, 15°C, 5°C hulless barley seedlings, and at the same time soaked the hulless barley seeds with a 1 µM melatonin solution for 12 hours before the hulless barley seeds germinated. Afterwards, the growth and physiological indicators of hulless barley seedlings under different treatment conditions were determined. Meanwhile, the qRT-PCR method was used to determine the transcription level of the hulless barley circadian clock genes under different treatment conditions under continuous light conditions.ResultsThe results showed the possible mechanism by which melatonin pretreatment can promote the growth of hulless barley under cold stress conditions by studying the effect of melatonin on the rhythm of the circadian clock system and some physiological indicators. The results revealed that the application of 1 µM melatonin could alleviate the growth inhibition of hulless barley seedlings caused by cold stress. In addition, exogenous melatonin could also restore the circadian rhythmic oscillation of circadian clock genes, such as HvCCA1 and HvTOC1, whose circadian rhythmic phenotypes were lost due to environmental cold stress. Additionally, the results confirmed that exogenous melatonin even reduced the accumulation of key physiological indicators under cold stress, including malondialdehyde and soluble sugars.DiscussionOverall, these findings revealed an important mechanism that exogenous melatonin alleviated the inhibition of plant vegetative growths either by restoring the disrupted circadian rhythmic expression oscillations of clock genes, or by regulating the accumulation profiles of pivotal physiological indicators under cold stress.

Rola obszaru tylnego podwzgórza w generowaniu rytmu theta*

Streszczenie Rytm theta jest jednym z najlepiej zsynchronizowanych wzorców aktywności oscylacyjnej rejestrowanych w mózgach ssaków. U ludzi, rytm ten obserwowany jest podczas snu REM, nawigacji przestrzennej, procesów pamięciowych, analitycznych oraz językowych. Może być również traktowany jako nieswoisty marker stanów patologicznych ośrodkowego układu nerwowego, takich jak choroba Alzheimera czy padaczka. Główną strukturą zaangażowaną w generowanie wzorca aktywności bioelektrycznej, zarówno u ludzi, jak i u gryzoni (najczęściej badanych zwierząt laboratoryjnych), jest formacja hipokampa. Jej funkcjonowanie zależy od współdziałania wielu innych struktur układu nerwowego. Jedną z nich jest obszar tylnego podwzgórza, który jest istotnym elementem układów neuronalnych modulujących zdolność formacji hipokampa do generowania rytmu theta. Przedstawione w artykule wyniki badań podkreślają rolę obszaru tylnego podwzgórza, jako modulatora hipokampalnego rytmu theta, ale wykazują również, że obszar ten jest zdolny do samodzielnego, niezależnego od wpływu innych struktur, generowania rytmicznej aktywności theta.

Bmal1 Regulates the Redox Rhythm of HSPB1, and Homooxidized HSPB1 Attenuates the Oxidative Stress Injury of Cardiomyocytes.

Oxidative stress is the main cause of acute myocardial infarction (AMI), which is related to the disorder of the regulation of Bmal1 on the redox state. HSPB1 form homologous-oxidized HSPB1 (homooxidized HSPB1) to resist oxidative damage via S-thiolated modification. However, it is still unclarified whether there is an interaction between the circadian clock and HSPB1 in myocardial injury. A total of 118 AMI patients admitted and treated in our hospital from Sep. 2019 to Sep. 2020 were selected to detect the plasma HSPB1 expression and the redox state. We divided the AMI patients into three subgroups: morning-onset AMI (5 : 00 am to 8 : 00 am; Am-subgroup, n = 38), noon-onset AMI (12 : 00 pm to 15 : 00; Pm-subgroup, n = 45), and night-onset AMI (20 : 00 pm to 23 : 00 pm; Eve-subgroup, n = 35) according to the circadian rhythm of onset. The Am-subgroup had remarkably higher cardiac troponin I (cTnI), creatine kinase MB (CK-MB), and B-type natriuretic peptide (BNP) but lower left ventricular ejection fraction (LVEF) than the Pm-subgroup and Eve-subgroup. Patients complicated with cardiogenic shock were significantly higher in the Am-subgroup than in the other two groups. The homooxidized HSPB1 in plasma markedly decreased in the Am-subgroup. The HSPB1C141S mutant accelerated H9c2 cell apoptosis, increased reactive oxygen species (ROS), and decreased reduced-glutathione (GSH) and the ratio of reduced-GSH and GSSG during oxidative stress. Importantly, we found that the redox state of HSPB1 was consistent with the oscillatory rhythm of Bmal1 expression in normal C57B/L mice. The circadian rhythm disorder contributed to decrease Bmal1 and homooxidized HSPB1 in cardiomyocytes of C57BL/6 mice. In addition, Bmal1 and homooxidized HSPB1 decreased in neonatal rat cardiomyocytes exposed to H2O2. Knockdown of Bmal1 led to significant attenuation in homooxidized HSPB1 expression, whereas overexpression of Bmal1 increased homooxidized HSPB1 expression in response to H2O2. Our findings indicated that the homooxidized HSPB1 reduced probably the AMI patients' risk of shock and target organ damage, which was associated with Bmal1 regulating the redox state of HSPB1.

Features of blood`s microcirculation at physical loads

This research deals with the study of blood microcirculation peculiarities.Materials and methods. 72 students of Bogdan Khmelnytsky Melitopol State Pedagogical University, aged 18–19, were examined. The experimental research consisted of the study of blood microcirculation functional state by means of Laser Doppler flowmetry (LDF) method. It helped to evaluate the state of tissue blood-circulation and to detect individual-typological peculiarities of blood microcirculation under the influence of physical activity (before and after exercise).Results. Three types of blood microcirculation were identified by using LDF-metry. The normoemic type of blood microcirculation, characterized by the superposition of oscillatory rhythms and reflected the balance of the mechanisms of regulation of microcirculation. The hyperemic type, characterized by a «monotonous» LDF-gram with a high parameter of microcirculation, which reflects the relative predominance of metabolic mechanisms in the regulation of microcirculation. The hypoemic type, characterized by a «monotonous» LDF-gram with a low parameter of the microcirculation parameter, which reflects the decrease of vasomotor mechanisms in the regulation of microcirculation. According to the LDF-metric data, the examined students under intensive physical activity have a significant increase in microcirculatory status: by 6 % of the microcirculation parameter, by 28 % of the mean square deviation and by 45 % of the initial value of the coefficient of variation.Conclusions. This dynamics of microcirculation shows that under the influence of physical exertion, a person creates significant functional reserves for the redistribution of blood flow and for more perfect intraorgan capillary blood flow. It was found, that in the process of physical activity, morpho-functional rearrangements of the human cardiovascular system occur. This reaction is formed by several components of blood microcirculation: blood flow in the transport direction, regulating blood supply in accordance with the needs of tissues and the exchange component of the histochemical barrier

Ambivalent Affines: Law Like Literature

This short essay will dwell upon the ‘law of literature and the literature of law’, as illuminated in the enduring scholarship and intellectual legacy of Peter Fitzpatrick. Reading with Fitzpatrick, we must grapple with a law that is both constituted and subverted by recourse to the supplement of fiction. These ambivalent ‘affines’, law and literature, share in an oscillatory rhythm: each is constituted and enlivened by an unbounded exteriority, yet each must be rendered normatively determinate. I reflect upon the ways in which Fitzpatrick’s account of ‘law like literature’ grasps and hones the methodological challenge implicit in this reading: to read law as literature and literature as law. Yet further, I extend a reading of Fitzpatrick’s scholarship that acknowledges this fictive law as not merely susceptible to but constituted by decoloniality.