Weak Stimulation Research Articles

Impacts of family care for children and the elderly on women's employment: evidence from rural China.

China's traditional culture makes rural women and men take on different family responsibilities. Use "China Family Panel Studies" (CFPS) data and build Logit and propensity score matching models to empirically study the impact of children care and elderly care on rural married women going out to work. And explore the welfare effects of basic education public services in helping rural women take care of their families. The results show that caring for children has a significant hindering effect on rural married women's job hunting. Especially for those in low-income families, the employment inhibition is most significant among women aged 20-30 with multiple children. Contrary to previous cognition, supporting the elderly has a certain weak stimulating effect. The kindergarten public services in rural areas can help women take care of their children and relieve their work pressure. The primary school public services have not played a role in alleviating them. This shows that there are still a large number of female laborers in rural China who are unable to go out to work due to family care. The improvement of rural basic education public services can promote more rural women going out to work. This finding will provide a policy reference for the introduction of a formal care system and the establishment of basic education public services in China.

Long-term depression induction and maintenance across regions of the apical branch of CA1 dendrites.

Well known as the center for learning and memory, hippocampus is the crucial brain region to study synaptic plasticity in the context of cellular fundamental mechanisms such as long-term depression (LTD) and long-term potentiation (LTP). However, despite years of extensive research, the key to our LTD queries and their induction mechanisms has not been fully understood. Previously, we reported the induction of late-LTD (L-LTD) in the distally located synapses of apical branch of hippocampal CA1 dendrites using strong low-frequency stimulation (SLFS). In contrast synapses at the proximal site could not express L-LTD. Thus, in the present study, we wanted to investigate whether or not synapses of apical dendritic branch at the proximal location could induce and maintain LTD and its related properties in in vitro rat hippocampal slices. Results indicated that the SLFS in the distal and proximal region triggered the plasticity related proteins (PRP) synthesis in both regions, as evident by the induction and maintenance of L-LTD in the distal region by virtue of synaptic and cross-tagging. In addition, the application of emetine at the time of proximal input stimulation prevented the transition of early-LTD (E-LTD) into L-LTD at the distal region, proving PRP synthesis at the proximal site. Further, it was observed that weak low-frequency stimulation (WLFS) could induce E-LTD in the proximal region along with LTD-specific tag-setting at the synapses. In conclusion, the current study suggests unique findings that the synaptic and cross-tagging mediate L-LTD expression is maintained in the proximal location of hippocampus apical CA1 dendrites.

Frequency-domain analysis of membrane polarization in two-compartment model neurons with weak alternating electric fields.

Transcranial alternating current stimulation (tACS) is widely used in studying brain functions and the treatment of neuropsychiatric diseases in a frequency-specific manner. However, how tACS works on neuronal activity has been poorly understood. In this paper, we use linear system analysis to investigate how weak alternating electric fields (EFs) affect the membrane polarization of neurons in the frequency domain. Two biophysically realistic conductance-based two-compartment models of cortical pyramidal neurons are developed to simulate subthreshold membrane polarization with weak alternating EFs. We linearize the original nonlinear models at the stable equilibrium points and further simplify them to the two- or three-dimensional linear systems. Thus, we calculate the transfer functions of the low-dimensional linear models to model neuronal polarization patterns. Based on the transfer functions, we compute the amplitude- and phase-frequency characteristics to describe the relationship between weak EFs and membrane polarization. We also computed the parameters (gain, zeros, and poles) and structures (the number of zeros and poles) of transfer functions to reveal how neuronal intrinsic properties affect the parameters and structure of transfer functions and thus the frequency-dependent membrane polarization with alternating EFs. We find that the amplitude and phase of membrane polarization both strongly depended on EF frequency, and these frequency responses are modulated by the intrinsic properties of neurons. The compartment geometry, internal coupling conductance, and ionic currents (except Ih) affect the frequency-dependent polarization by mainly changing the gain and pole of transfer functions. Larger gain contributes to larger amplitude-frequency characteristics. The closer the pole is to the imaginary axis, the lower phase-frequency characteristics. However, Ih changes the structure of transfer function in the dendrite by introducing a new pair of zero-pole points, which decrease the amplitude at low frequencies and thus lead to a visible resonance. These results highlight the effects of passive properties and active ion currents on subthreshold membrane polarization with alternating EFs in the frequency domain, which provide an explainable connection of how intrinsic properties of neurons modulate the neuronal input-output functions with weak EF stimulation.

Effects of active and sham tDCS on the soleus H-reflex during standing

Weak transcranial direct current stimulation (tDCS) is known to affect corticospinal excitability and enhance motor skill acquisition, whereas its effects on spinal reflexes in actively contracting muscles are yet to be established. Thus, in this study, we examined the acute effects of Active and Sham tDCS on the soleus H-reflex during standing. In fourteen adults without known neurological conditions, the soleus H-reflex was repeatedly elicited at just above M-wave threshold throughout 30 min of Active (N = 7) or Sham (N = 7) 2-mA tDCS over the primary motor cortex in standing. The maximum H-reflex (Hmax) and M-wave (Mmax) were also measured before and immediately after 30 min of tDCS. The soleus H-reflex amplitudes became significantly larger (by 6%) ≈1 min into Active or Sham tDCS and gradually returned toward the pre-tDCS values, on average, within 15 min. With Active tDCS, the amplitude reduction from the initial increase appeared to occur more swiftly than with Sham tDCS. An acute temporary increase in the soleus H-reflex amplitude within the first minute of Active and Sham tDCS found in this study indicates a previously unreported effect of tDCS on the H-reflex excitability. The present study suggests that neurophysiological characterization of Sham tDCS effects is just as important as investigating Active tDCS effects in understanding and defining acute effects of tDCS on the excitability of spinal reflex pathways.

A model of zinc dynamics evoked by intense stimulation at the cleft of hippocampal mossy fiber synapses.

Zinc is a transition metal that is particularly abundant in the mossy fibers of the hippocampal CA3 area. Despite the large number of studies about the zinc role in mossy fibers, the action of zinc in synaptic mechanisms is only partly known. The use of computational models can be a useful tool for this study. In a previous work, a model was developed to evaluate zinc dynamics at the mossy fiber synaptic cleft, following weak stimulation, insufficient to evoke zinc entry into postsynaptic neurons. For intense stimulation, cleft zinc effluxes must be considered. Therefore, the initial model was extended to include postsynaptic zinc effluxes based on the Goldman-Hodgkin-Katz current equation combined with Hodgkin and Huxley conductance changes. These effluxes occur through different postsynaptic escape routes, namely L- and N-types voltage-dependent calcium channels and NMDA receptors. For that purpose, various stimulations were assumed to induce high concentrations of cleft free zinc, named as intense (10μM), very intense (100μM) and extreme (500μM). It was observed that the main postsynaptic escape routes of cleft zinc are the L-type calcium channels, followed by the NMDA receptor channels and by N-type calcium channels. However, their relative contribution for cleft zinc clearance was relatively small and decreased for higher amounts of zinc, most likely due to the blockade action of zinc in postsynaptic receptors and channels. Therefore, it can be concluded that the larger the zinc release, the more predominant the zinc uptake process will be in the cleft zinc clearance.

Asymmetric cell division safeguards memory CD8 T cell development

The strength of Tcell receptor (TCR) stimulation and asymmetric distribution of fate determinants are both implied to affect Tcell differentiation. Here, we uncover asymmetric cell division (ACD) as a safeguard mechanism for memory CD8 Tcell generation specifically upon strong TCR stimulation. Using live imaging approaches, we find that strong TCR stimulation induces elevated ACD rates, and subsequent single-cell-derived colonies comprise both effector and memory precursor cells. The abundance of memory precursor cells emerging from a single activated Tcell positively correlates with first mitosis ACD. Accordingly, preventing ACD by inhibition of protein kinase Cζ (PKCζ) during the first mitosis upon strong TCR stimulation markedly curtails the formation of memory precursor cells. Conversely, no effect of ACD on fate commitment is observed upon weak TCR stimulation. Our data provide relevant mechanistic insights into the role of ACD for CD8 Tcell fate regulation upon different activation conditions.

TCR/Chimeric Antigen Receptor (CAR) Cross-Antagonism to Fine-Tune CAR-T cell Immunotherapy

Abstract Chimeric antigen receptor (CAR) T cells, are created by extracting T cells from a cancer patient, engineering them to express a CAR targeting a tumor specific molecule, then reintroducing them back into the patient. A patient’s T cells contain their own endogenous T cell receptors (TCRs) however, which could potentially interact with the exogenous CAR inserted into the cell. In this study, we examine how TCR and CAR signals interact upon CAR-T activation. We show that weak TCR stimulation can reduce (antagonize) or increase overall CAR-T response, both in vitro and in vivo, across multiple tumor models, in both mouse and human T cells. We further show that the behavior of these TCR/CAR interactions can be manipulated by changing various characteristics of the TCR, CAR, and associated ligands. While this behavior is complex, we show that it can be described by a single mathematical model based on the adaptive kinetic proofreading scheme of ligand discrimination. We conclude by presenting potential applications for cancer immunotherapy. Intramural Research Program of the National Cancer Institute

Elucidation of the mechanism underlying impaired sensorimotor gating in patients with primary blepharospasm using prepulse inhibition.

We aimed to analyze prepulse inhibition (PPI) impairment of the blink reflex in patients with primary blepharospasm (BSP). We recruited 30 BSP patients and 20 gender- and age-matched healthy controls (HCs). Weak electrical stimulation was applied to the right index finger at interstimulus intervals (ISIs) of 120, 200, and 300 ms before the supraorbital nerve stimulation to investigate PPI size [PPI size = (1 - R2 area at prepulse trials/R2 area at baseline trials) × 100%]. The prepulse stimulus significantly inhibited the R 2 component at the three ISIs in both groups, but less inhibition was shown in the BSP group (p < 0.05). In HCs, the prepulse stimulus induced prolonged R 2 and R 2c latencies at the three ISIs and increased the R 1 amplitude at ISIs of 120 ms; these changes were absent in BSP patients. In the BSP group, patients with sensory tricks showed better PPI than patients without sensory tricks. Disease duration and motor symptom severity showed no significant correlation with PPI size. In BSP patients, PPI was impaired while R 1 facilitation was absent. PPI size did not correlate with the motor symptom severity and disease duration. Patients with sensory tricks showed better PPI than those without sensory tricks.

The phosphatidylinositol-transfer protein Nir3 promotes PI(4,5)P2 replenishment in response to TCR signaling during T cell development and survival

Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phospholipase C-γ (PLCγ1) represents a critical step in T cell antigen receptor (TCR) signaling and subsequent thymocyte and T cell responses. PIP2 replenishment following its depletion in the plasma membrane (PM) is dependent on delivery of its precursor phosphatidylinositol (PI) from the endoplasmic reticulum (ER) to the PM. We show that a PI transfer protein (PITP), Nir3 (Pitpnm2), promotes PIP2 replenishment following TCR stimulation and is important for T cell development. In Nir3–/– T lineage cells, the PIP2 replenishment following TCR stimulation is slower. Nir3 deficiency attenuates calcium mobilization in double-positive (DP) thymocytes in response to weak TCR stimulation. This impaired TCR signaling leads to attenuated thymocyte development at TCRβ selection and positive selection as well as diminished mature T cell fitness in Nir3–/– mice. This study highlights the importance of PIP2 replenishment mediated by PITPs at ER-PM junctions during TCR signaling.

Mechanisms of Action of Noninvasive Brain Stimulation with Weak Non-Constant Current Stimulation Approaches.

Objective: Non-constant current stimulation (NCCS) is a neuromodulatory method in which weak alternating, pulsed or random currents are delivered to the human head via scalp or earlobe electrodes. This approach is widely used in basic and translational studies. However, the underlying mechanisms of NCCS, which lead to biological and behavioral effects in the brain, remain largely unknown. In this review, we characterize NCCS techniques currently being utilized in neuroscience investigations, including transcranial alternating current stimulation (tACS), transcranial pulsed current stimulation (tPCS), transcranial random noise stimulation (tRNS), and cranial electrotherapy stimulation (CES). Method: We unsystematically searched all relevant conference papers, journal articles, chapters, and textbooks on the biological mechanisms of NCCS techniques. Results: The fundamental idea of NCCS is that these low-level currents can interact with neuronal activity, modulate neuroplasticity and entrain cortical networks, thus, modifying cognition and behavior. We elucidate the mechanisms of action for each NCCS technique. These techniques may cause microscopic effects (such as affecting ion channels and neurotransmission systems) and macroscopic effects (such as affecting brain oscillations and functional connectivity) on the brain through different mechanisms of action (such as neural entrainment and stochastic resonance). Conclusion: The appeal of NCCS is its potential to modulate neuroplasticity noninvasively, along with the ease of use and good tolerability. Promising and interesting evidence has been reported for the capacity of NCCS to affect neural circuits and the behaviors under their control. Today, the challenge is to utilize this advancement optimally. Continuing methodological advancements with NCCS approaches will enable researchers to better understand how NCCS can be utilized for the modulation of nervous system activity and subsequent behaviors, with possible applications to non-clinical and clinical practices.

Does the selection of virtual reality video matter? A laboratory experimental study of the influences of arousal

Despite the increasing number of studies on virtual tourism, there is currently little knowledge regarding the significance of the selection of appropriate virtual reality video (e.g., content stimulus) to marketing. This study explored how virtual reality video stimulation (arousal) elicited user flow experience and subsequent satisfaction using the stimulus-organism-response (SOR) paradigm. Analysis of the data revealed that self-reported arousal had a statistically significant impact on enjoyment, time distortion, and focused attention. Similar effects on enjoyment and time distortion were found by respiration rate. The results also demonstrated that user satisfaction was influenced by enjoyment and control. The PLS-SEM analysis further demonstrated that enjoyment partially mediated the effects of self-reported arousal and respiration rate on satisfaction. According to multigroup analysis, self-reported arousal (heart rate) exhibited a greater influence on enjoyment (time distortion) across two groups (weak versus strong stimulation). Theoretical and practical implications of these findings were discussed.

Self-forming electroactive dynamic membrane for enhancing the decolorization of methyl orange by weak electrical stimulation

An electroactive dynamic membrane (EADM), which enabled simultaneous solid-liquid separation and contaminants removal, has been developed by electrostimulation using domestic wastewater as inoculum. Results showed that both the control dynamic membrane (CDM), without electrical stimulation, and the EADM systems exhibited stable removal performance with chemical oxygen demand (COD), and a robustness in responding to a fluctuating organic load. With the introduction of a weak electrical field, the EADM transmembrane pressure (TMP) was significantly reduced (0.02 kPa/d) compared with the control (0.20 kPa/d). In the treatment of methyl orange (MO), the EADM system achieved a decolorization efficiency of 85.87 %, much higher than the control dynamic membrane (CDM) system (58.84 %), which can be attributed to electrical stimulation and H2 production on cathode. Microbial analysis has established that electrostimulation enriched the electroactive bacteria in the dynamic biofilm, and shaped the microbial structure, with improved contaminant removal. The results of this study highlight the potential of regulating the microbial community and creating a beneficial biofilm as a dynamic layer to facilitate contaminant removal.

Resistance of &lt;i&gt;Rhodococcus ruber&lt;/i&gt; biofilms to CuO nanoparticles depending on exopolymer matrix composition

Background. The widespread use of copper oxide nanoparticles (CuO NPs) increases their release into the environment, which leads to accumulation in trophic chains. Bacterial biofilms are more resistant to physico-chemical factors compared to planktonic cells due to an exopolymer matrix (EPM) consisting of polysaccharides, proteins, lipids and nucleic acids. Rhodococcus actinobacteria are promising for environmental biotechnology due to biodegradation of petroleum products, pesticides and other organic pollutants, as well as bioaccumulation of heavy metals. The aim. To investigate effects of CuO NPs on the viability of Rhodococcus ruber IEGM 231 cells in biofilms and the dynamics of EPM components. Methods. R. ruber biofilms were grown on microscopy cover glass with CuO NPs and EPM components were studied using confocal laser scanning microscopy (CLSM) by differentiating staining with LIVE/DEAD to determine the number of living and dead cells, Nile Red for lipids, FITC for proteins and Calcofluor White for betapolysaccharides. Results. It was found that R. ruber biofilms grown in a mineral medium with1.0 vol.% n-hexadecane are more resistant to CuO NPs compared to biofilms growing in a rich culture medium (meat-peptone broth). This was due to more intensive EPM formation, which plays a major role in protecting cells from the bactericidal action of nanometals. A weak stimulating effect of a low (0.001 g/l) concentration of CuO NPs on biofilm formation was registered. Dynamics and localization of main EPM components were monitored during prolonged (24–72 h) biofilm cultivation with CuO NPs. When exposed to high (0.01–0.1 g/l) concentrations of CuO NPs, a consistently high lipid content and an increase in concentrations of polysaccharides and proteins were revealed. Conclusion. Understanding the complex interaction mechanisms of nanometals and biofilms will contribute to the development of effective biocatalysts based on immobilized bacterial cells. Also, the obtained data can be used to combat unwanted biofilms with the help of metal nanoparticles.

Safety and efficacy of electrical stimulation for lower-extremity muscle weakness in intensive care unit 2019 Novel Coronavirus patients: A phase I double-blinded randomized controlled trial.

Intensive care unit (ICU) prolonged immobilization may lead to lower-extremity muscle deconditioning among critically ill patients, particularly more accentuated in those with 2019 Novel Coronavirus (COVID-19) infection. Electrical stimulation (E-Stim) is known to improve musculoskeletal outcomes. This phase I double-blinded randomized controlled trial examined the safety and efficacy of lower-extremity E-Stim to prevent muscle deconditioning. Critically ill COVID-19 patients admitted to the ICU were randomly assigned to control (CG) or intervention (IG) groups. Both groups received daily E-Stim (1 h) for up to 14 days on both gastrocnemius muscles (GNMs). The device was functional in the IG and non-functional in the CG. Primary outcomes included ankle strength (Ankles) measured by an ankle-dynamometer, and GNM endurance (GNMe) in response to E-Stim assessed with surface electromyography (sEMG). Outcomes were measured at baseline, 3 and 9 days. Thirty-two (IG = 16, CG = 16) lower extremities in 16 patients were independently assessed. The mean time between ICU admission and E-Stim therapy delivery was 1.8 ± 1.9 days (p = 0.29). At 3 days, the IG showed an improvement compared to the CG with medium effect sizes for Ankles (p = 0.06, Cohen's d = 0.77) and GNMe (p = 0.06, d = 0.69). At 9 days, the IG GNMe was significantly higher than the CG (p = 0.04, d = 0.97) with a 6.3% improvement from baseline (p = 0.029). E-Stim did not alter vital signs (i.e., heart/respiratory rate, blood saturation of oxygen), showed no adverse events (i.e., pain, skin damage, discomfort), nor interfere with ICU standard of care procedures (i.e., mechanical ventilation, prone rotation). This study supports the safety and efficacy of early E-Stim therapy to potentially prevent deterioration of lower-extremity muscle conditions in critically ill COVID-19 patients recently admitted to the ICU. If confirmed in a larger sample, E-Stim may be used as a practical adjunctive therapy. [https://clinicaltrials.gov/], identifier [NCT04685213].

Prevention of alloimmune rejection using XBP1-deleted bone marrow-derived dendritic cells in heart transplantation.

Genetically modified dendritic cells (DCs) modulate the alloimmunity of T lymphocytes by regulating antigen presentation. We generated mice with specific deletion of the X-box-binding protein 1 (XBP1) allele in bone marrow cells and cultured bone marrow-derived DCs (Xbp1-/- BMDCs) from these animals. We then tested the phenotype of Xbp1-/- BMDCs, evaluated their capability to activate allogeneic T cells and investigated their mechanistic actions. We developed a mouse model of allogeneic heart transplantation in which recipients received PBS, Xbp1-/- BMDCs, a suboptimal dose of cyclosporine A (CsA), or Xbp1-/- BMDCs combined with a suboptimal dose of CsA to evaluate the effects of Xbp1-/- BMDC transfusion on alloimmunity and on the survival of heart allografts. The deletion of XBP1 in BMDCs exploited the IRE1-dependent decay of TAPBP mRNA to reduce the expression of MHC-I on the cell surface, altered the capability of BMDCs to activate CD8+ T cells, and ultimately suppressed CD8+ T-cell-mediated allogeneic rejection. The adoptive transfer of Xbp1-/- BMDCs inhibited CD8+ T-cell-mediated rejection. In addition, XBP1-deficient BMDCs were weak stimulators of allogeneic CD4+ T cells despite expressing high levels of MHC-II and costimulatory molecules on their cell surface. Moreover, the adoptive transfer of Xbp1-/- BMDCs inhibited the production of circulating donor-specific IgG. The combination of Xbp1-/- BMDCs and CsA treatment significantly prolonged the survival of allografts compared to CsA alone. The deletion of XBP1 induces immunosuppressive BMDCs, and treatment with these immunosuppressive BMDCs prevents alloimmune rejection and improves the outcomes of heart transplantation. This finding provides a promising therapeutic target in combating transplant rejection and expands knowledge of inducing therapeutic DCs.

Target Site of Prepulse Inhibition of the Trigeminal Blink Reflex in Humans.

Despite the clinical significance of prepulse inhibition (PPI), the mechanisms are not well understood. Herein, we present our investigation of PPI in the R1 component of electrically induced blink reflexes. The effect of a prepulse was explored with varying prepulse test intervals (PTIs) of 20-600 ms in 4 females and 12 males. Prepulse-test combinations included the following: stimulation of the supraorbital nerve (SON)-SON [Experiment (Exp) 1], sound-sound (Exp 2), the axon of the facial nerve-SON (Exp 3), sound-SON (Exp 4), and SON-SON with a long trial-trial interval (Exp 5). Results showed that (1) leading weak SON stimulation reduced SON-induced ipsilateral R1 with a maximum effect at a PTI of 140 ms, (2) the sound-sound paradigm resulted in a U-shaped inhibition time course of the auditory startle reflex (ASR) peaking at 140 ms PTI, (3) facial nerve stimulation showed only a weak effect on R1, (4) a weak sound prepulse facilitated R1 but strongly inhibited SON-induced late blink reflexes (LateRs) with a similar U-shaped curve, and (5) LateR in Exp 5 was almost completely absent at PTIs >80 ms. These results indicate that the principal sensory nucleus is responsible for R1 PPI. Inhibition of ASR or LateR occurs at a point in the startle reflex circuit where auditory and somatosensory signals converge. Although the two inhibitions are different in location, their similar time courses suggest similar neural mechanisms. As R1 has a simple circuit and is stable, R1 PPI helps to clarify PPI mechanisms.SIGNIFICANCE STATEMENT Prepulse inhibition (PPI) is a phenomenon in which the startle response induced by a startle stimulus is suppressed by a preceding nonstartle stimulus. This study demonstrated that the R1 component of the trigeminal blink reflex shows clear PPI despite R1 generation within a circuit consisting of the trigeminal and facial nuclei, without startle reflex circuit involvement. Thus, PPI is not specific to the startle reflex. In addition, PPI of R1, the auditory startle reflex, and the trigeminal late blink reflex showed similar time courses in response to the prepulse test interval, suggesting similar mechanisms regardless of inhibition site. R1 PPI, in conjunction with other paradigms with different prepulse-test combinations, would increase understanding of the underlying mechanisms.

Debiasing the Disposition Effect with Noninvasive Brain Stimulation: The Role of Cognitive Control

This study tests whether modulating a brain region associated with cognitive control using noninvasive brain stimulation affects the disposition effect. A participant trades stocks in an experimental asset market while their level of cognitive control is exogenously manipulated by applying weak current stimulation to a control-related cortical region. We find that the stimulation significantly affects the participant’s cognitive control and tendency to exhibit the disposition effect. This result is also obtained for financial professionals. We thus provide evidence that cognitive control is important for the disposition effect. This paper was accepted by Bruno Biais, finance. Funding: X. Niu acknowledges financial support from the National Natural Science Foundation of China [Grant 72203132], Taishan Scholar Program of Shandong Province [Grant tsqn201909013], and Natural Science Foundation of Shandong Province [Grant ZR2022QG048]. J. Li acknowledges financial support from the National Social Science Foundation of China [Grant 20AZD044], Natural Science Foundation of Shandong Province [Grant ZR2022MG068], and Project of Humanities and Social Sciences of Shandong University [Grant 21RWZD15]. Q. Cao acknowledges financial support from the Social Science Foundation of Jiangsu Province [Grant 21GLC006]. The authors also acknowledge financial support from the Major Project of the National Natural Science Foundation of China [Grant 72192842]. Supplemental Material: The data files and online appendix are available at https://doi.org/10.1287/mnsc.2022.4596 .

Different coding characteristics between flight and freezing in dorsal periaqueductal gray of mice during exposure to innate threats.

Flight and freezing are two vital defensive behaviors that mice display to avoid natural enemies. When they are exposed to innate threats, visual cues are processed and transmitted by the visual system into the emotional nuclei and finally transmitted to the periaqueductal gray (PAG) to induce defensive behaviors. However, how the dorsal PAG (dPAG) encodes the two defensive behaviors is unclear. Multi-array electrodes were implanted in the dPAG nuclei of C57BL/6 mice. Two kinds of visual stimuli (looming and sweeping) were used to induce defensive behaviors in mice. Neural signals under different defense behaviors were recorded, and the encoding characteristics of the two behaviors were extracted and analyzed from spike firing and frequency oscillations. Finally, synchronization of neural activity during the defense process was analyzed. The neural activity between flight and freezing behaviors showed different firing patterns, and the differences in the inter-spike interval distribution were mainly reflected in the 2-10ms period. The frequency band activities under both defensive behaviors were concentrated in the theta band; the active frequency of flight was ~8 to 10Hz, whereas that of freezing behavior was ~6 to 8Hz. The network connection density under both defense behaviors was significantly higher than the period before and after defensive behavior occurred, indicating that there was a high synchronization of neural activity during the defense process. The dPAG nuclei of mice have different coding features between flight and freezing behaviors; during strong looming stimulation, fast neuro-instinctive decision making is required while encountering weak sweeping stimulation, and computable planning late behavior is predicted in the early stage. The frequency band activities under both defensive behaviors were concentrated in the theta band. There was a high synchronization of neural activity during the defense process, which may be a key factor triggering different defensive behaviors.

Olanzapine enhances adipogenesis and suppresses lipolysis in 3T3‑L1 adipocytes under low‑glucose and weak differentiation/maturation conditions.

Olanzapine, a second-generation antipsychotic used in the treatment of schizophrenia, is classified as a multi-acting receptor-targeted antipsychotic. Abnormal weight gain is one of the most common side effects of this drug, along with an increased appetite and food intake. However, weight gain has also been reported in patients taking olanzapine without an increase in appetite. Olanzapine has been reported to be directly associated with enhanced adipogenesis; however, whether olanzapine increases lipid content in adipocytes under weak stimulus conditions, such as low glucose concentrations and weak differentiation and/or maturation conditions, is poorly understood. The present study examined the stimulatory effect of olanzapine during the differentiation and maturation of 3T3-L1 pre-adipocytes under low-glucose and weak stimulation conditions by evaluating the expression levels of PPARγ by western blotting and oil red O staining. Western blotting revealed that olanzapine suppressed perilipin phosphorylation, which is an important lipolysis step in adipocytes. The findings of the present study provide novel insights to explain weight gain in patients taking olanzapine but not presenting with increased food intake.

In vivo low-intensity magnetic pulses durably alter neocortical neuron excitability and spontaneous activity.

Magnetic brain stimulation is a promising treatment for neurological and psychiatric disorders. However, a better understanding of its effects at the individual neuron level is essential to improve its clinical application. We combined focal low-intensity repetitive transcranial magnetic stimulation (LI-rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neurons in vivo. Continuous 10Hz LI-rTMS reliably evoked firing at ∼4-5Hz during the stimulation period and induced durable attenuation of synaptic activity and spontaneous firing in cortical neurons, through membrane hyperpolarization and a reduced intrinsic excitability. However, inducing firing in individual neurons by repeated intracellular current injection did not reproduce the effects of LI-rTMS on neuronal properties. These data provide a novel understanding of mechanisms underlying magnetic brain stimulation showing that, in addition to inducing biochemical plasticity, even weak magnetic fields can activate neurons and enduringly modulate their excitability. KEY POINTS: Repetitive transcranial magnetic stimulation (rTMS) is a promising technique to alleviate neurological and psychiatric disorders caused by alterations in cortical activity. Our knowledge of the cellular mechanisms underlying rTMS-based therapies remains limited. We combined in vivo focal application of low-intensity rTMS (LI-rTMS) to the rat somatosensory cortex with intracellular recordings of subjacent pyramidal neurons to characterize the effects of weak magnetic fields at single cell level. Ten minutes of LI-rTMS delivered at 10Hz reliably evoked action potentials in cortical neurons during the stimulation period, and induced durable attenuation of their intrinsic excitability, synaptic activity and spontaneous firing. These results help us better understand the mechanisms of weak magnetic stimulation and should allow optimizing the effectiveness of stimulation protocols for clinical use.