Biallelic variants in α-tubulin isotypes cause female infertility characterised as recurrent preimplantation embryo arrest.

BACKGROUND: Recurrent preimplantation embryo developmental arrest (RPEA) is the most common phenotype in assisted reproductive technology treatment failure associated with identified genetic abnormalities. Currently known maternal genetic variants explain only a limited number of cases. Variants of the ß-tubulin subunit gene, TUBB8, cause oocyte meiotic arrest and RPEA through a broad spectrum of spindle defects. In contrast, α-tubulin subunit genes are poorly studied in the context of preimplantation embryonic development. METHODS: Whole exome sequencing was performed on the PREA cohort. Functional characterisations of the identified candidate disease-causing variants were validated using Sanger sequencing, bioinformatics, in vitro functional analyses and single-cell RNA-sequencing of arrested embryos. RESULTS: Four homozygous variants were identified in the PREA cohort: two of TUBA1C (p.Gln358Ter and p.Asp444Metfs*42) and two of TUBA4A (p.Arg339Cys and p.Tyr440Ter). These variants cause varying degrees of spindle assembly defects. Additionally, we characterised changes in the human arrested embryo transcriptome carrying TUBA4A variants, with a particular focus on spindle organisation, chromosome segregation and mRNA decay. CONCLUSION: Our findings identified TUBA1C as a novel genetic marker and expanded the genetic and phenotypic spectrum of TUBA4A in female infertility and RPEA, which altogether highlighted the importance of α-tubulin isotypes in preimplantation embryonic development.

Mechanistic study of the transmission pattern of the SARS-CoV-2 omicron variant.

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) characterized by 30 mutations in its spike protein, has rapidly spread worldwide since November 2021, significantly exacerbating the ongoing COVID-19 pandemic. In order to investigate the relationship between these mutations and the variant's high transmissibility, we conducted a systematic analysis of the mutational effect on spike-angiotensin-converting enzyme-2 (ACE2) interactions and explored the structural/energy correlation of key mutations, utilizing a reliable coarse-grained model. Our study extended beyond the receptor-binding domain (RBD) of spike trimer through comprehensive modeling of the full-length spike trimer rather than just the RBD. Our free-energy calculation revealed that the enhanced binding affinity between the spike protein and the ACE2 receptor is correlated with the increased structural stability of the isolated spike protein, thus explaining the omicron variant's heightened transmissibility. The conclusion was supported by our experimental analyses involving the expression and purification of the full-length spike trimer. Furthermore, the energy decomposition analysis established those electrostatic interactions make major contributions to this effect. We categorized the mutations into four groups and established an analytical framework that can be employed in studying future mutations. Additionally, our calculations rationalized the reduced affinity of the omicron variant towards most available therapeutic neutralizing antibodies, when compared with the wild type. By providing concrete experimental data and offering a solid explanation, this study contributes to a better understanding of the relationship between theories and observations and lays the foundation for future investigations.

Spectral recovery of broadband waveforms via cross-phase modulation based tunable Talbot amplifier.

Physical processes in the Fourier domain play a crucial role in various applications such as spectroscopy, quantum technology, ranging, radio-astronomy, and telecommunications. However, the presence of stochastic noise poses a significant challenge in the detection of broadband spectral waveforms, especially those with limited power. In this study, we propose and experimentally demonstrate a cross-phase modulation (XPM) based spectral Talbot amplifier to recover the broadband spectral waveforms in high fidelity. Through the combination of spectral phase filtering and XPM nonlinear effect in an all-fiber configuration, we demonstrate spectral purification of THz-bandwidth spectral waveforms submerged in strong noise. The proposed spectral Talbot amplifier provides tunable amplification factors from 3 to 10, achieved by flexible control on the temporal waveform of the pump and the net dispersion. We demonstrate up to 10-dB remarkable improvement on optical signal-to-noise ratio (OSNR) while preserving the spectral envelope. Furthermore, our system allows frequency-selective reconstruction of noisy input spectra, introducing a new level of flexibility for spectral recovery and information extraction. We also evaluate numerically the impact of pump intensity deviation on the reconstructed spectral waveforms. Our all-optical approach presents a powerful means for effective recovery of broadband spectral waveforms, enabling information extraction from a noise-buried background.

Development of a Preoperative Screening Tool to Reduce Morbidity and Mortality of COVID-19-positive Hepatobiliary Patients.

PURPOSE: This study aimed to create a preoperative risk assessment form for COVID-19-positive hepatobiliary patients to guide further prevention of complications after surgery and reduce morbidity and mortality. DESIGN: Based on the literature, focus groups, and case studies, a multidisciplinary panel of 15 experts conducted three rounds of a Delphi study that resulted in the development of a preoperative risk assessment form to be used by healthcare professionals in the treatment of COVID-19-positive hepatobiliary patients. METHODS: A preoperative risk assessment form for health professionals to use among COVID-19-positive hepatobiliary patients was developed based on literature, focus groups, and case studies. A 3-round Delphi study was conducted to validate and revise the risk assessment form using a multidisciplinary panel of 15 experts involved in hepatobiliary surgery. FINDINGS: The experts demonstrated high cooperation and familiarity with the research topic, with positive coefficients ranging from 93.33% to 100% and authority coefficients ranging from 0.83 to 0.86. The coordination coefficients were 0.33, 0.26, and 0.22, respectively, indicating good coordination among expert opinions. The final risk assessment form included 9 primary (first-level) indicators, 38 secondary (second-level) indicators, and 122 tertiary (third-level) indicators. CONCLUSIONS: The preoperative risk assessment form for hepatobiliary surgery patients infected with COVID-19 is scientifically rigorous, reliable, and valid. This screening tool may be used by health providers to identify high-risk patients, prevent postoperative complications, and reduce morbidity and mortality.

Effects of traditional Chinese culture-based bibliotherapy on the spiritual health of patients with liver cancer.

BACKGROUND: Liver cancer is a serious global health problem and is associated with poor spiritual health. Bibliotherapy is beneficial in improving health outcomes in cancer patients, yet there is a lack of empirical evidence of its effect on the spiritual health of liver cancer patients in China. The study aimed to investigate the effects of bibliotherapy based on Chinese traditional culture on the spiritual health of patients with liver cancer in China. This study was approved by the Ethics Committee of Hunan Normal University School of Medicine and registered with the Chinese Clinical Trial Registry with the registration (No: 2021260), which registration in June 30th 2021. METHODS: A total of 60 patients with liver cancer were divided into the intervention group (n = 30) and the control group (n = 30) through WeChat. The intervention group received bibliotherapy therapy based on traditional Chinese culture, while the control group received routine care. Spiritual health was assessed using the Spiritual Attitude and Involvement List (SAIL) and compared before and after the intervention between the two groups. The chi-square test and t-test were used to analyze the intervention effects. RESULTS: The two groups were comparable in all baseline characteristics including the SAIL score. After 5 weeks of intervention, the score of SAIL increased significantly from 96.76 ± 15.08 to 106.93 ± 13.82 in the intervention group (t = - 29.380, p < 0.001), while no significant difference in SAIL score was observed in the control group (from 95.27 ± 16.40 to 95.31 ± 16.24, t = - 0.189, p = 0.852). Similar patterns were also observed in its three dimensions of connecting with oneself, connecting with the environment, and connecting with transcendence. CONCLUSIONS: Our study showed that bibliotherapy based on traditional Chinese culture using the WeChat platform can greatly improve the spiritual health of patients with liver cancer and has the potential to be widely applied to cancer patients to improve their well-being.

The important role of glial transmitters released by astrocytes in Alzheimer's disease: A perspective from dynamical modeling.

This paper aims to establish a coupling model of neuronal populations and astrocytes and, on this basis, explore the possible mechanism of electroencephalography (EEG) slowing in Alzheimer's disease (AD) from the viewpoint of dynamical modeling. First and foremost, excitatory and inhibitory time constants are shown to induce the early symptoms of AD. The corresponding dynamic nature is mainly due to changes in the amplitude and frequency of the oscillatory behavior. However, there are also a few cases that can be attributed to the change of the oscillation mode caused by the limit cycle bifurcation and birhythmicity. Then, an improved neural mass model influenced by astrocytes is proposed, considering the important effects of glutamate and adenosine triphosphate (ATP) released by astrocytes on the synaptic transmission process reported in experiments. The results show that a dysfunctional astrocyte disrupts the physiological state, causing three typical EEG slowing phenomena reported clinically: the decreased dominant frequency, the decreased rhythmic activity in the α band, and the increased rhythmic activity in the δ+θ band. In addition, astrocytes may control AD when the effect of ATP on synaptic connections is greater than that of glutamate. The control rate depends on the ratio of the effect of glutamate on excitatory and inhibitory synaptic connections. These modeling results can not only reproduce some experimental and clinical results, but, more importantly, may offer a prediction of some underlying phenomena, helping to inspire the disease mechanisms and therapeutic methods of targeting astrocytes.

Tunable optical frequency comb with hundred-GHz spacings generated on a silicon waveguide.

We demonstrate the generation of optical frequency combs with tunable spacing at the hundred-GHz range in the 1550-nm window. The widely spaced combs are realized through silicon-based cross-phase modulation. The optical pump is prepared by multiplication of a 10-GHz train of 1.7-ps pedestal-free pulses. Energy-efficient temporal Talbot processing is used to multiply the repetition rate by a factor of up to 20. In our approach, the multiplication factor can be flexibly controlled by tuning the temporal dispersion inside an optical processor. Optical frequency combs with spacings ranging from 140 to 200 GHz have been successfully generated with a maximum carrier-to-noise suppression ratio of ∼45 dB.

Dynamical Mechanism Analysis of Three Neuroregulatory Strategies on the Modulation of Seizures.

This paper attempts to explore and compare the regulatory mechanisms of optogenetic stimulation (OS), deep brain stimulation (DBS) and electromagnetic induction on epilepsy. Based on the Wilson-Cowan model, we first demonstrate that the external input received by excitatory and inhibitory neural populations can induce rich dynamic bifurcation behaviors such as Hopf bifurcation, and make the system exhibit epileptic and normal states. Then, both OS and DBS are shown to be effective in controlling the epileptic state to a normal low-level state, and the stimulus parameters have a broad effective range. However, electromagnetic induction cannot directly control epilepsy to this desired state, even if it can significantly reduce the oscillation frequency of neural populations. One main difference worth noting is that the high spatiotemporal specificity of OS allows it to target inhibitory neuronal populations, whereas DBS and electromagnetic induction can only stimulate excitatory as well as inhibitory neuronal populations together. Next, the propagation behavior of epilepsy is explored under a typical three-node feedback loop structure. An increase in coupling strength accelerates and exacerbates epileptic activity in other brain regions. Finally, OS and DBS applied to the epileptic focus play similar positive roles in controlling the behavior of the area of seizure propagation, while electromagnetic induction still only achieves unsatisfactory effects. It is hoped that these dynamical results can provide insights into the treatment of epilepsy as well as other neurological disorders.

Global simulation of fine resolution land use/cover change and estimation of aboveground biomass carbon under the shared socioeconomic pathways.

Land use change driven by human activities plays a critical role in the terrestrial carbon budget through habitat loss and vegetation change. Despite the projections of the global population and economic growth under the framework of the Shared Socioeconomic Pathways (SSPs), little is known of land use/cover change (LUCC) at a fine spatial resolution and how carbon pools respond to LUCC under different SSPs. This study projected the future global LUCC with 1 km spatial resolution and a 10-year time step from 2010 to 2100 and then explored its direct impacts on aboveground biomass carbon (AGB) under SSPs. Scenario SSP3 yields the highest global cropland expansion, among which approximately 48% and 46% is expected to be located in the current forest land and grassland, respectively. Scenario SSP1 has the largest forest expansion and is mainly converted from grassland (54%) and cropland (30%). Due to the spatial change in land use/cover, global AGB loss is expected to reach approximately 3.422 Pg C in 2100 under scenario SSP3 and increases by approximately 0.587 Pg C under scenario SSP1. Africa is expected to lose 30% of AGB under the scenario SSP3. Aboveground biomass in Asia will fix 0.774 Pg C to reverse the AGB loss in 2100 under scenario SSP1. The global carbon loss estimated by the land use products with 10 km and 25 km resolution are less than that with 1 km by 1.5% (ranging from -11.2% in Africa to +34.0% in Oceania) and 2.9% (ranging from -11.8% in Africa to +24.0% in Oceania), respectively. These findings suggest that sufficient spatial details in the existing SSP scenario projections could reduce the uncertainties of AGB assessment, and reasonable land use development and management is a key measure to mitigate the negative impacts of LUCC on the biomass carbon pool.

Application of Coarse-Grained (CG) Models to Explore Conformational Pathway of Large-Scale Protein Machines.

Protein machines are clusters of protein assemblies that function in order to control the transfer of matter and energy in cells. For a specific protein machine, its working mechanisms are not only determined by the static crystal structures, but also related to the conformational transition dynamics and the corresponding energy profiles. With the rapid development of crystallographic techniques, the spatial scale of resolved structures is reaching up to thousands of residues, and the concomitant conformational changes become more and more complicated, posing a great challenge for computational biology research. Previously, a coarse-grained (CG) model aiming at conformational free energy evaluation was developed and showed excellent ability to reproduce the energy profiles by accurate electrostatic interaction calculations. In this study, we extended the application of the CG model to a series of large-scale protein machine systems. The spike protein trimer of SARS-CoV-2, ATP citrate lyase (ACLY) tetramer, and P4-ATPases systems were carefully studied and discussed as examples. It is indicated that the CG model is effective to depict the energy profiles of the conformational pathway between two endpoint structures, especially for large-scale systems. Both the energy change and energy barrier between endpoint structures provide reasonable mechanism explanations for the associated biological processes, including the opening of receptor binding domain (RBD) of spike protein, the phospholipid transportation of P4-ATPase, and the loop translocation of ACLY. Taken together, the CG model provides a suitable alternative in mechanistic studies related to conformational change in large-scale protein machines.

Predicting Mutational Effects on Receptor Binding of the Spike Protein of SARS-CoV-2 Variants.

The pandemic caused by SARS-CoV-2 has cost millions of lives and tremendous social/financial loss. The virus continues to evolve and mutate. In particular, the recently emerged "UK", "South Africa", and Delta variants show higher infectivity and spreading speed. Thus, the relationship between the mutations of certain amino acids and the spreading speed of the virus is a problem of great importance. In this respect, understanding the mutational mechanism is crucial for surveillance and prediction of future mutations as well as antibody/vaccine development. In this work, we used a coarse-grained model (that was used previously in predicting the importance of mutations of N501) to calculate the free energy change of various types of single-site or combined-site mutations. This was done for the UK, South Africa, and Delta mutants. We investigated the underlying mechanisms of the binding affinity changes for mutations at different spike protein domains of SARS-CoV-2 and provided the energy basis for the resistance of the E484 mutant to the antibody m396. Other potential mutation sites were also predicted. Furthermore, the in silico predictions were assessed by functional experiments. The results establish that the faster spreading of recently observed mutants is strongly correlated with the binding-affinity enhancement between virus and human receptor as well as with the reduction of the binding to the m396 antibody. Significantly, the current approach offers a way to predict new variants and to assess the effectiveness of different antibodies toward such variants.

Enhanced CSPR for a multichannel Kramers-Kronig receiver by self-seeded stimulated Brillouin scattering.

We demonstrate carrier-to-signal power ratio (CSPR) enhancement by self-seeded stimulated Brillouin scattering to improve the performance of Kramers-Kronig (KK) detection for multichannel single-sideband (SSB) signals. By virtue of low-CSPR transmission and high-CSPR detection, our proposed scheme effectively advances system performance by reducing propagation-induced distortion while maintaining the minimum phase condition. We experimentally demonstrate the improvement in CSPR and bit error rate of 5×10-Gbaud 16-QAM SSB signals by applying the carrier recovery block after 80-km transmission. Under optimum pump power, the average Q factor improvement of all five channels is 3.0 dB. We also analyze the performances of different channels and the major limiting factor. The results verify that our scheme offers a promising solution to enhance SSB self-coherent KK detection in wavelength-division multiplexing systems.

Control analysis of electrical stimulation for epilepsy waveforms in a thalamocortical network.

Physiological experiments and computational models both show that the thalamic reticular nucleus (RE) participates in inducing various firing patterns of cortex. Absence seizure, featured by 2-4 Hz spike-wave discharges (SWD) oscillation, is a high incidence of disease in children. Lots of electrophysiological experiments have verified the correlation between absence seizures and RE, however, the dynamical mechanisms are not well understood. Based on previous Taylor model, we firstly study the effects of external input and self-inhibition of RE on epilepsy transition. We show that increasing external input and self-inhibition of RE can lead the system from epileptic state to normal state, and vice versa. Next, we explore two stimulus strategies added in RE and various transition behaviors can be induced, such as high saturated state to clonic. Meanwhile, as the intensity of stimulation increasing, they can not only suppress the SWD, but also produce tonic-clonic oscillation. Finally, the control of DBS on single neuron cluster and two neuron clusters are compared and we find stimulating RE and TC simultaneously is a superior mode to stimulate anyone of RE or TC. It is hoped that the results we obtained will have an enlightenment on clinical treatment.

DNA-binding mechanisms of human and mouse cGAS: a comparative MD and MM/GBSA study.

Cyclic GMP-AMP synthase (cGAS) can detect the presence of cytoplasmic DNA and activate the innate immune system via the cGAS-STING pathway. Although several structures of cGAS-DNA complexes were resolved recently, the molecular mechanism of cGAS in its recognition of DNA has not yet been fully understood. In order to reveal the subtle differences between human and mouse cGAS in terms of their DNA-binding mechanisms, four systems, both human and mouse cGAS in complex with two different DNA sequences of equal length, were studied by molecular dynamics simulations and molecular mechanics/generalized Born surface area analysis. Several residues, including ARG176/ARG161, ARG195/ARG180, ASN210/ASN196, LYS384/LYS372, CYM397/CYM385, LYS403/LYS391, LYS407/LYS395, and LYS411/LYS399, were identified to be the common key residues in the recognition of DNA for cGAS in both humans and mice. In addition, four residue pairs LYS173/ARG158, ASP177/LYS162, CYS199/LYS184, and GLU398/SER387 were suggested to be the major residues that make human cGAS and mouse cGAS different in terms of their binding to DNA. Besides the well-known zinc-thumb domain, two residues at the kink of the spine helix were also proposed for the first time to be the major binding motifs in cGAS-DNA interaction.

Dynamic Transitions of Epilepsy Waveforms Induced by Astrocyte Dysfunction and Electrical Stimulation.

Experimental studies have shown that astrocytes participate in epilepsy through inducing the release of glutamate. Meanwhile, considering the disinhibition circuit among inhibitory neuronal populations with different time scales and the feedforward inhibition connection from thalamic relay nucleus to cortical inhibitory neuronal population, here, we propose a modified thalamocortical field model to systematically investigate the mechanism of epilepsy. Firstly, our results show that rich firing activities can be induced by astrocyte dysfunction, including high or low saturated state, high- or low-frequency clonic, spike-wave discharge (SWD), and tonic. More importantly, with the enhancement of feedforward inhibition connection, SWD and tonic oscillations will disappear. In other words, all these pathological waveforms can be suppressed or eliminated. Then, we explore the control effects after different external stimulations applying to thalamic neuronal population. We find that single-pulse stimulation can not only suppress but also induce pathological firing patterns, such as SWD, tonic, and clonic oscillations. And we further verify that deep brain stimulation can control absence epilepsy by regulating the amplitude and pulse width of stimulation. In addition, based on our modified model, 3 : 2 coordinated reset stimulation strategies with different intensities are compared and a more effective and safer stimulation mode is proposed. Our conclusions are expected to give more theoretical insights into the treatment of epilepsy.

Do obesity and low levels of physical activity increase the risk for developing type 2 diabetes mellitus among women with prior gestational diabetes in rural China?

Moderate-to-vigorous intensity physical activity (MVPA) and obesity play important roles in the development of type 2 diabetes mellitus (T2DM) among women with prior gestational diabetes mellitus (GDM). Yet, how MVPA affects the risk of developing T2DM among women with prior GDM across the different categories of obesity indicators is unclear. This study aimed to describe the levels of postpartum abnormal glucose tolerance (AGT), obesity indicators (body mass index [BMI] and waist circumference [WC]), and MVPA and to explore the independent effect and joint effect of MVPA and obesity indicators (BMI and WC) on the risk for developing AGT among women with prior GDM in rural China. A total of 425 women with prior GDM were recruited from two county-level hospitals in Western and Eastern Hunan, China. Data were collected with self-reported measurements on sociodemographics and clinical factors as well as postpartum weight-related behaviors (physical activity and dietary intake). The 75-g oral glucose tolerance test, weight, height, and WC were measured on site. Binary logistic regression models and multiplitive interaction models were used to explore the independent and joint associations of BMI and MVPA as well as WC and MVPA on AGT, respectively. One-fifth (20.9%) of the sample women had AGT. The obesity indicators were significantly associated with an increased risk of postpartum AGT, but MVPA was not. In joint effect analyses, larger WC and insufficient MVPA were not significantly associated with increased risk of AGT compared with normal WC and sufficient MVPA (mutually adjusted odds ratio [OR], 1.43; 95% confidence interval [CI], 0.46-4.43; p > .05). In joint effect analyses of MVPA and BMI, the mutually adjusted OR for developing AGT in women who were obese and had insufficient MVPA was 4.49 (95% CI, 1.35-14.92; p < .05) compared with normal weight and sufficient MVPA. Adequate weight management and increased MVPA are warranted for Chinese women with prior GDM to prevent T2DM.

Chemoselective P(NMe2)3-Mediated Reductive Epoxidation between Two Different Carbonyl Electrophiles: Synthesis of Highly Functionalized Unsymmetrical Epoxides.

Herein, we report a chemoselective P(NMe2)3-mediated reductive epoxidation of α-dicarbonyl compounds such as isatins, α-keto esters, and α-diketones with aldehydes and ketones, leading to an efficient synthesis of a wide range of highly functionalized unsymmetrical epoxides in moderate to excellent yields and diastereoselectivities. The Kukhtin-Ramirez adduct, which is exclusively generated in situ from an α-dicarbonyl compound and P(NMe2)3, plays a key role in governing the chemoselectivity. It represents the first practical synthesis of unsymmetrical epoxides via direct reductive epoxidation of two different carbonyl electrophiles and also complements the existing methods of generating epoxides.

Predicting seizure by modeling synaptic plasticity based on EEG signals - a case study of inherited epilepsy.

This paper explores the internal dynamical mechanisms of epileptic seizures through quantitative modeling based on full brain electroencephalogram (EEG) signals. Our goal is to provide seizure prediction and facilitate treatment for epileptic patients. Motivated by an earlier mathematical model with incorporated synaptic plasticity, we studied the nonlinear dynamics of inherited seizures through a differential equation model. First, driven by a set of clinical inherited electroencephalogram data recorded from a patient with diagnosed Glucose Transporter Deficiency, we developed a dynamic seizure model on a system of ordinary differential equations. The model was reduced in complexity after considering and removing redundancy of each EEG channel. Then we verified that the proposed model produces qualitatively relevant behavior which matches the basic experimental observations of inherited seizure, including synchronization index and frequency. Meanwhile, the rationality of the connectivity structure hypothesis in the modeling process was verified. Further, through varying the threshold condition and excitation strength of synaptic plasticity, we elucidated the effect of synaptic plasticity to our seizure model. Results suggest that synaptic plasticity has great effect on the duration of seizure activities, which support the plausibility of therapeutic interventions for seizure control.

Traveling Theta Waves in the Human Hippocampus.

The hippocampal theta oscillation is strongly correlated with behaviors such as memory and spatial navigation, but we do not understand its specific functional role. One hint of theta's function came from the discovery in rodents that theta oscillations are traveling waves that allow parts of the hippocampus to simultaneously exhibit separate oscillatory phases. Because hippocampal theta oscillations in humans have different properties compared with rodents, we examined these signals directly using multielectrode recordings from neurosurgical patients. Our findings confirm that human hippocampal theta oscillations are traveling waves, but also show that these oscillations appear at a broader range of frequencies compared with rodents. Human traveling waves showed a distinctive pattern of spatial propagation such that there is a consistent phase spread across the hippocampus regardless of the oscillations' frequency. This suggests that traveling theta oscillations are important functionally in humans because they coordinate phase coding throughout the hippocampus in a consistent manner. Significance statement: We show for the first time in humans that hippocampal theta oscillations are traveling waves, moving along the length of the hippocampus in a posterior-anterior direction. The existence of these traveling theta waves is important for understanding hippocampal neural coding because they cause neurons at separate positions in the hippocampus to experience different theta phases simultaneously. The theta phase that a neuron measures is a key factor in how that cell represents behavioral information. Therefore, the existence of traveling theta waves indicates that, to fully understand how a hippocampal neuron represents information, it is vital to also account for that cell's location in addition to conventional measures of neural activity.

Control effects of stimulus paradigms on characteristic firings of parkinsonism.

Experimental studies have shown that neuron population located in the basal ganglia of parkinsonian primates can exhibit characteristic firings with certain firing rates differing from normal brain activities. Motivated by recent experimental findings, we investigate the effects of various stimulation paradigms on the firing rates of parkinsonism based on the proposed dynamical models. Our results show that the closed-loop deep brain stimulation is superior in ameliorating the firing behaviors of the parkinsonism, and other control strategies have similar effects according to the observation of electrophysiological experiments. In addition, in conformity to physiological experiments, we found that there exists optimal delay of input in the closed-loop GPtrain|M1 paradigm, where more normal behaviors can be obtained. More interestingly, we observed that W-shaped curves of the firing rates always appear as stimulus delay varies. We furthermore verify the robustness of the obtained results by studying three pallidal discharge rates of the parkinsonism based on the conductance-based model, as well as the integrate-and-fire-or-burst model. Finally, we show that short-term plasticity can improve the firing rates and optimize the control effects on parkinsonism. Our conclusions may give more theoretical insight into Parkinson's disease studies.