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Posttraumatic stress disorder (PTSD), a psychiatric disorder caused by stressful events, is characterized by long-lasting fear memory. The nucleus accumbens shell (NAcS) is a key brain region that regulates fear-associated behavior. Small-conductance calcium-activated potassium channels (SK channels) play a key role in regulating the excitability of NAcS medium spiny neurons (MSNs) but their mechanisms of action in fear freezing are unclear. We established an animal model of traumatic memory using conditioned fear freezing paradigm, and investigated the alterations in SK channels of NAc MSNs subsequent to fear conditioning in mice. We then utilized an adeno-associated virus (AAV) transfection system to overexpress the SK3 subunit and explore the function of the NAcS MSNs SK3 channel in conditioned fear freezing. Fear conditioning activated NAcS MSNs with enhanced excitability and reduced the SK channel-mediated medium after-hyperpolarization (mAHP) amplitude. The expression of NAcS SK3 were also reduced time-dependently. The overexpression of NAcS SK3 impaired conditioned fear consolidation without affecting conditioned fear expression, and blocked fear conditioning-induced alterations in NAcS MSNs excitability and mAHP amplitude. Additionally, the amplitudes of mEPSC, AMPAR/NMDAR ratio, and membrane surface GluA1/A2 expression in NAcS MSNs was increased by fear conditioning and returned to normal levels upon SK3 overexpression, indicating that fear conditioning-induced decrease of SK3 expression caused postsynaptic excitation by facilitating AMPAR transmission to the membrane. These findings show that the NAcS MSNs SK3 channel plays a critical role in conditioned fear consolidation and that it may influence PTSD pathogenesis, making it a potential therapeutic target against PTSD. [Display omitted] [ABSTRACT FROM AUTHOR]

This article proposes a novel model predictive control for a three-phase permanent-magnet synchronous motor (PMSM) with enhanced robustness against parameter variation and higher current control precision. First, the extended set of voltage vectors are adopted to increase the current control precision. Then, the parameter sensitivity problem is avoided in the first stage using an indirect reference vector strategy for the sake of computation time reduction. Subsequently, the inductance disturbance observer is adopted in the current prediction process to enhance the robustness against machine parameter mismatch. The intrinsic connection between the discrete control sets precision and disturbance observer is analyzed. The proposed method improves the robustness against parameter mismatch and current control precision simultaneously. Experimentations are conducted to verify the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

This paper presents a model predictive control for a six-phase permanent magnet synchronous machine (PMSM) with a reduced-dimension cost function. Only the variables in the harmonic subspace are included into the cost function, while the energy conversion related variables are excluded. This is achieved by using the deadbeat direct torque and flux control method to obtain a reference voltage vector and then to track the torque and stator flux properly in the energy conversion related subspace. Then, according to the position of the reference vector, the appropriate prediction vectors can be determined. Subsequently, a reduced-dimension cost function including only the harmonic constraints is defined to evaluate the feasible prediction vectors. In this way, the predictive model and the cost function are simplified without redundant constraints. Meanwhile, the torque and flux can be regulated satisfactorily, and the harmonic currents are suppressed effectively. Finally, experimental results of the proposed method and the conventional model predictive torque control are presented in this paper to verify the validity of the proposed method. [ABSTRACT FROM AUTHOR]

This paper proposes a multi-vector-based model predictive torque control with fixed switching frequency for a six-phase permanent-magnet synchronous machine to improve its steady-state performance. First, two active vectors are synthesized in each control period to suppress the stator current harmonics in x–y subspace. For the sake of easy implementation in the real-time system, the vectors are artfully synthesized in two different manners. Second, to achieve the fixed switching frequency, two null vectors are inserted along with the synthesized vector. The duty ratio of the null vectors is determined based on the principle of deadbeat torque control. In the meantime, the synthesized vector and its duty ratio are evaluated simultaneously by the cost function. In this way, the torque ripple can be reduced considerably. Thus, with the proposed method, both the current harmonics and the torque ripple are reduced effectively. Also, the proposed methodology can be readily implemented practically under the constant switching frequency. Finally, the experimentation is carried out to verify the validity of the proposed method. [ABSTRACT FROM AUTHOR]

This paper proposes a low-complexity model predictive flux control (MPFC) with current harmonics and torque ripple reduced for a six-phase permanent magnet synchronous machine (PMSM) motor. First, the virtual vectors in two different magnitudes are adopted for the sake of harmonic currents and torque ripple reduction, as well as simplifying the predictive model by eliminating the z1–z2 variables from the cost function. Then, a look-up table is developed to exclude the useless voltage vectors in advance. In this way, the number of prediction vectors is reduced and heavy computation burden is alleviated. Moreover, to avoid the tedious tuning work of the weighting factor in the cost function, the torque and flux amplitude are transformed into an equivalent reference flux vector. Thus, the complexity of the cost function is significantly reduced. Meanwhile, the current and torque performance are highly improved using the proposed method. Also, the fast dynamic response of predictive control is retained. Finally, simulation and experimental results are offered to verify the effectiveness of the proposed MPFC method. [ABSTRACT FROM AUTHOR]

This paper proposes a novel deadbeat current control (DBCC)-based model predictive control for an asymmetrical six-phase permanent magnet synchronous machine. First, the solution of DBCC is adopted to obtain the expected reference voltage vector (RVV). Then, two groups of virtual vectors, in the total number of 24 with different magnitudes, are defined for the sake of current harmonics suppression. Subsequently, two in-phase virtual vectors which are closest to the RVV are selected as the prediction vectors. The next step is to define a cost function which is composed of the error between the RVV and the available prediction vectors. Then, the selected two virtual vectors are evaluated and the one that minimizes the cost function will be applied in the next instant. In this way, only two prediction vectors need to be evaluated and the computation burden is highly alleviated. In the meantime, the weighting factor involved in predictive torque control is avoided. In addition, to achieve the readily implementation with standard pulsewidth modulation switching sequence, 18 virtual vectors are artfully replaced by their corresponding equivalent virtual vectors. Finally, the proposed method is comparatively studied and compared with other benchmark methods. Simulation and experimental results are offered to confirm the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

This paper presents a novel model predictive torque control with discrete duty ratio optimization for a six-phase PMSM machine with high robustness against weighting factor variation. First, a two-step lookup table is developed to initially select the optimal voltage vector, which is to regulate the torque and flux in the energy conversion related subspace, as well as suppress the harmonic currents in the x–y subspace. Then, a null vector is inserted along with the selected optimal voltage vector to adjust the duty ratio with a set of value to avoid the complicated derivation. Subsequently, the optimal duty ratio is determined by a cost function to minimize the torque and flux error. So by using the proposed method, the torque ripple is reduced and even applying an improper weighting factor will not deteriorate the machine performance severely. Finally, experimentations are carried out to verify the validity of the proposed method. [ABSTRACT FROM AUTHOR]

This paper proposes a model predictive control scheme based remedial control for the single-phase open-circuit fault of an asymmetrical six-phase PMSM machine. The proposed strategy adopts the normal vector space decomposition transformation matrix without reconfiguring the controller topology. The key is to derive the perturbation term of the prediction vectors in α-β and x-y subspace, which is based on the difference of the faulty phase voltage under healthy and faulty condition. Through the compensation of the prediction vectors, the predictive model can be accurately described in the faulty condition. Thus, the current variables in the next instant is accurately predicted and the torque fluctuation is suppressed. Finally, the experimental results are provided to verify the validity of the proposed method on pre- and post-fault tolerant operation. [ABSTRACT FROM AUTHOR]

This study presents a finite‐control‐set model predictive current control (FCS‐MPCC) with phase shift compensation for a cost‐effective voltage source inverter. Firstly, the FCS‐MPCC algorithm uses the discrete‐time model of the inverter to predict the coming value of the load current. In addition, a cost function is defined to evaluate all possible voltage vectors from the inverter, where the cost function is selected. Moreover, a pulse computation module is developed to obtain the final switching signals for insulated‐gate bipolar transistors. In addition, the problem of current distortion caused by phase shift is solved by employing a time interval compensation factor. Furthermore, a comparison between the hysteresis control, pulse‐width modulation control, and proposed predictive control is presented in terms of the steady‐state and dynamic performances. Both simulation and experiment are conducted, which confirm the validity of the proposed control scheme of FCS‐MPCC. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that gut microbiota and its metabolites can influence the brain function and the related behaviors. Trimethylamine N-oxide (TMAO), an indirect metabolite of gut microbiota, has been linked to aging, cognitive impairment, and many brain disorders. However, the potential effects of TMAO on social behaviors remain elusive. The present study investigated the effects of early life systemic TMAO exposure and intra-hippocampal TMAO infusion during adulthood on social behaviors in mice. We also analyzed the effects of intra-hippocampus infusion of TMAO during adulthood on levels of metabolites. The results showed that both systemic TMAO exposure in the post-weaning period and intra-hippocampal TMAO infusion during adulthood decreased social rank and reduced sexual preference in adult mice. Data from LC-MS metabolomics analysis showed that intra-hippocampal TMAO infusion induced a total 207 differential metabolites, which belongs to several metabolic or signaling pathways, especially FoxO signaling pathway and retrograde endocannabinoid signaling pathway. These data suggest that TMAO may affect social behaviors by regulating metabolites in the hippocampus, which may provide a new insight into the role of gut microbiota in regulating social behaviors. • Long-lasting effects of postweaning TMAO exposure on mice were observed. • Intra-hippocampal TMAO infusion affects social behaviors of adult mice. • TMAO can induce abnormal sexual preference and lower social dominance of mice. • Hippocampal metabolism is involved in behavioral abnormalities caused by TMAO. [ABSTRACT FROM AUTHOR]

Recent studies found that non‐coding RNAs (ncRNAs) played crucial roles in drug addiction through epigenetic regulation of gene expression and underlying drug‐induced neuroadaptations. In this study, we characterized lncRNA transcriptome profiles in the nucleus accumbens (NAc) of mice exhibiting morphine‐conditioned place preference (CPP) and explored the prospective roles of novel differentially expressed lncRNA, lncLingo2 and its derived miR‐876‐5p in the acquisition of opioids‐associated behaviours. We found that the lncLingo2 was downregulated within the NAc core (NAcC) but not in the NAc shell (NAcS). This downregulation was found to be associated with the development of morphine CPP and heroin intravenous self‐administration (IVSA). As Mfold software revealed that the secondary structures of lncLingo2 contained the sequence of pre‐miR‐876, transfection of LV‐lncLingo2 into HEK293 cells significantly upregulated miR‐876 expression and the changes of mature miR‐876 are positively correlated with lncLingo2 expression in NAcC of morphine CPP trained mice. Delivering miR‐876‐5p mimics into NAcC also inhibited the acquisition of morphine CPP. Furthermore, bioinformatics analysis and dual‐luciferase assay confirmed that miR‐876‐5p binds to its target gene, Kcnn3, selectively and regulates morphine CPP training‐induced alteration of Kcnn3 expression. Lastly, the electrophysiological analysis indicated that the currents of small conductance calcium‐activated potassium (SK) channel was increased, which led to low neuronal excitability in NAcC after CPP training, and these changes were reversed by lncLingo2 overexpression. Collectively, lncLingo2 may function as a precursor of miR‐876‐5p in NAcC, hence modulating the development of opioid‐associated behaviours in mice, which may serve as an underlying biomarker and therapeutic target of opioid addiction. [ABSTRACT FROM AUTHOR]

Introduction: Several studies have linked inflammation and oxidative stress with the pathogenesis of depression. Artesunate is a commonly used medication to treat malaria and has been shown to produce antioxidant, anti‐inflammatory, and immunomodulatory effects. However, its prophylactic effects on depression and depression‐related brain pathology are unknown. Methods: In Experiment 1, using a PC12 cell line, we investigated whether artesunate can prevent hydrogen peroxide (H2O2)‐induced oxidative injury that mimics oxidative stress commonly observed in the depressed brain. Next, using lipopolysaccharide (LPS)‐induced mouse model of depression, we investigated whether artesunate can prevent behavioral deficits observed in the open field test, novelty‐suppressed feeding test, sucrose preference test, forced swimming test, and tail suspension procedure. Results: We found that artesunate significantly prevented a H2O2‐induced reduction in PC12 cell activity, suggesting its antioxidant potential. We also found that mice pretreated with artesunate (5, 15 mg/kg) intraperitoneally (i.p.) prior to the LPS (.8 mg/kg, i.p.) treatment showed fewer and less severe depression‐ and anxiety‐like behaviors than the LPS‐treated control mice. Conclusion: Our findings indicate that artesunate produces antioxidant effect, as well as antidepressant and anxiolytic effects. Importantly, our findings first demonstrate that artesunate can prevent LPS‐induced depression‐ and anxiety‐like symptoms, strongly suggesting its prophylactic potential in the treatment of depression and, perhaps, other psychiatric disorders associated with inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Background Drug memories that associate drug-paired stimuli with the effects of abused drugs contribute to relapse. Exposure to drug-associated contexts causes consolidated drug memories to be in a labile state, during which manipulations can be given to impair drug memories. Although substantial evidence demonstrates the crucial role of neuronal signaling in addiction, little is known about the contribution of astrocyte-neuron communication. Methods Rats were trained for cocaine-induced conditioned place preference (CPP) or self-administration and microinjected with the glycogen phosphorylation inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol into the basolateral amygdala (BLA) immediately after retrieval. The concentration of lactate was measured immediately after retrieval via microdialysis, and the CPP score and number of nosepokes were recorded 24 hours later. Furthermore, we used antisense oligodeoxynucleotides to disrupt the expression of astrocytic lactate transporters (monocarboxylate transporters 1 and 2) in the BLA after retrieval, tested the expression of CPP 1 day later, and injected L-lactate into the BLA 15 minutes before retrieval to rescue the effects of the oligodeoxynucleotides. Results Injection of 1,4-dideoxy-1,4-imino-D-arabinitol into the BLA immediately after retrieval prevented the subsequent expression of cocaine-induced CPP, decreased the concentration of lactate in the BLA, and reduced the number of nosepokes for cocaine self-administration. Disrupting the expression of monocarboxylate transporters 1 and 2 in the BLA also caused subsequent deficits in the expression of cocaine-induced CPP, which was rescued by pretreatment with L-lactate. Conclusions Our results suggest that astrocyte-neuron lactate transport in the BLA is critical for the reconsolidation of cocaine memory. [ABSTRACT FROM AUTHOR]

Background Conditioned fear memories can be updated by extinction during reconsolidation, and this effect is specific to the reactivated conditioned stimulus (CS). However, a traumatic event can be associated with several cues, and each cue can potentially trigger recollection of the event. We introduced a technique to target all diverse cues associated with an aversive event that causes fear. Methods In human experiments, 161 subjects underwent modified fear conditioning, in which they were exposed to an unconditioned stimulus (US) or unreinforced CS to reactivate the memory and then underwent extinction, spontaneous recovery, and reinstatement. In animal experiments, 343 rats underwent contextual fear conditioning under a similar protocol as that used in the human experiments. We also explored the molecular alterations after US reactivation in rats. Results Presentation of a lower intensity US before extinction disrupted the associations between the different CS and reactivated US in both humans and rats. This effect persisted for at least 6 months in humans and was selective to the reactivated US. This procedure was also effective for remote memories in both humans and rats. Compared with the CS, the US induced stronger endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptors 1 and 2 and stronger activation of protein kinase A, p70S6 kinase, and cyclic adenosine monophosphate response element binding protein in the dorsal hippocampus in rats. Conclusions These findings demonstrate that a modified US retrieval extinction strategy may have a potential impact on therapeutic approaches to prevent the return of fear. [ABSTRACT FROM AUTHOR]

• Atractylenolide III produces antidepressant- and anxiolytic-like effects in rat models. Atractylenolide III, a major component of the atractylodes macrocephala Koidz, derived from the rhizoma atractylodes , has been reported to produce various pharmacological effects including anti-aging, anti-inflammation, anti-tumor, and other effects. Growing evidence suggests that proinflammatory cytokines, such as interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α, are increased in depressed patients. The present study was aimed at investigating the antidepressant- and anxiolytic-like effects of atractylenolide III in lipopolysaccharide (LPS) challenge and chronic unpredictable mild stress (CUMS) rat model. We found that 30 mg/kg of atractylenolide III administered by oral gavage for 14 days, significantly reduced the immobility time in a forced swimming test (FST), but did not alter the number of crossings in an open field test (OFT), respectively. The results indicated that atractylenolide III has an antidepressant-like effect without affecting locomotor activity. We then used the LPS-induced depression model to assess the effects of atractylenolide III on behaviors in FST, sucrose preference test (SPT), and novelty-suppressed feeding test (NSFT). Interestingly, in addition to the antidepressant-like effects, 30 mg/kg of atractylenolide III also produced an anxiolytic-like effect. To further identify the antidepressant- and anxiolytic-like effects of atractylenolide III, we used the CUMS model with 28 consecutive days of the atractylenolide III treatment, followed by the SPT, FST, and NSFT. Atractylenolide III prevented CUMS-induced depressive- and anxiety-like behaviors in rats. To illustrate the underlying possible mechanisms of action of atractylenolide III, we measured the proinflammatory cytokines levels. The results showed that atractylenolide III decreased the proinflammatory cytokines levels in the hippocampus of CUMS exposed rats. In summary, our findings demonstrated that atractylenolide III produces antidepressant- and anxiolytic-like effects in rats, and these effects appear to be mediated by inhibition of hippocampal neuronal inflammation. [ABSTRACT FROM AUTHOR]

A progressive increase in drug craving following drug exposure is an important trigger of relapse. CircularRNAs (CircRNAs), key regulators of gene expression, play an important role in neurological diseases. However, the role of circRNAs in drug craving is unclear. In the present study, we trained mice to morphine conditioned place preference (CPP) and collected the nucleus accumbens (NAc) sections on abstinence day 1 (AD1) and day 14 (AD14) for RNA-sequencing. CircTmeff-1, which was highly expressed in the NAc core, was associated with incubation of context-induced morphine craving. The gain- and loss- of function showed that circTmeff-1 was a positive regulator of incubation. Simultaneously, the expression of miR-541–5p and miR-6934–3p were down-regulated in the NAc core during the incubation period. The dual luciferase reporter, RNA pulldown, and fluorescence insitu hybridization assays confirmed that miR-541–5p and miR-6934–3p bind to circTmeff-1 selectively. Furthermore, bioinformatics and western blot analysis suggested that vesicle-associated membrane protein 1 (VAMP1) and neurofascin (NFASC), both overlapping targets of miR-541–5p and miR-6934–3p, were highly expressed during incubation. Lastly, AAV-induced down-regulation of circTmeff-1 decreased VAMP1 and NFASC expression and incubation of morphine craving. These findings suggested that circTmeff-1, a novel circRNA, promotes incubation of context-induced morphine craving by sponging miR-541/miR-6934 in the NAc core. Thus, circTmeff-1 represents a potential therapeutic target for context-induced opioid craving, following prolonged abstinence. [Display omitted] [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is one of the most prevalently used illegal psychostimulants in many countries. Continuous exposure to METH leads to behavioral sensitization in animals, which can be used as a behavioral model with many mechanisms in common with relapse in humans. Molecular hydrogen has recently gained attention for its potential as a novel healthcare product with preventive and therapeutic applicability to a wide range of pathological conditions. However, it remains unclear whether and, if so, how hydrogen regulates METH-induced behavioral abnormalities. In the present study, we investigated the roles of molecular hydrogen on the acquisition and transfer of METH-induced behavioral sensitization and the accompanying changes in ERK phosphorylation and ΔFosB activation in the nucleus accumbens (NAc) of mice. To this end, male C57BL/6 mice received METH (0.1, 0.5 and 1.0 mg/kg, i.p.) injections for 7 days followed by a METH challenge (0.1, 0.5 and 1.0 mg/kg, i.p.) after a 7-day transfer period. Molecular hydrogen, delivered through a hydrogen-rich saline (HRS) injection (10 mL/kg, i.p., 3-h interval), was administered during the acquisition and transfer periods. We found that HRS administration was able to inhibit the acquisition and transfer of 0.1 and 0.5 mg/kg METH-induced behavioral sensitization to a certain extent, thereby attenuating the expression of behavioral sensitization. The HRS injections alone did not induce any obvious changes in locomotor activity in mice. Intriguingly, the increases in pERK and ΔFosB in the NAc, which accompanied the METH-induced behavioral sensitization, were also attenuated by the HRS treatments. Due to the anti-oxidative function of molecular hydrogen, the HRS injections reduced METH-induced reactive oxygen species and malondialdehyde generation in the NAc. These results suggest that molecular hydrogen serves as an anti-oxidative agent with potentially therapeutic applicability to the treatment of METH addicts. • Molecular hydrogen has previously been found to prevent morphine-withdrawal-induced negative affective states. • Molecular hydrogen was able to attenuate behavioral sensitization to a certain extent. • Molecular hydrogen was also shown to attenuate METH-induced accompanying increases of pERK and ΔFosB in NAc. • Molecular hydrogen may serve as an anti-oxidative agent with therapeutic potential in METH addiction. [ABSTRACT FROM AUTHOR]