Neuronomodulation of Excitable Neurons / 神经科学通报·英文版

Neuronomodulation refers to the modulation of neural conduction and synaptic transmission (i.e., the conduction process involved in synaptic transmission) of excitable neurons via changes in the membrane potential in response to chemical substances, from spillover neurotransmitters to paracrine or endocrine hormones circulating in the blood. Neuronomodulation can be direct or indirect, depending on the transduction pathways from the ligand binding site to the ion pore, either on the same molecule, i.e. the ion channel, or through an intermediate step on different molecules. The major players in direct neuronomodulation are ligand-gated or voltage-gated ion channels. The key process of direct neuronomodulation is the binding and chemoactivation of ligand-gated or voltage-gated ion channels, either orthosterically or allosterically, by various ligands. Indirect neuronomodulation involves metabotropic receptor-mediated slow potentials, where steroid hormones, cytokines, and chemokines can implement these actions. Elucidating neuronomodulation is of great significance for understanding the physiological mechanisms of brain function, and the occurrence and treatment of diseases.

Historia y principios básicos de la estimulación magnética transcraneal

La estimulación magnética transcraneal (EMT) es una técnica no invasiva que consiste en la utilización de campos magnéticos para estimular a las neuronas de la corteza cerebral. Si bien la electricidad se ha pretendido emplear previamente en el campo de la medicina, la historia de la EMT se remonta al descubrimiento de la inducción electromagnética, por Faraday, en el siglo XIX. Sin embargo, no fue hasta la década de 1980 cuando Anthony Barker, en la Universidad de Sheffield, desarrolló el primer dispositivo de EMT. La EMT funciona mediante una bobina colocada en el cuero cabelludo, la cual produce un campo magnético que puede atravesar el cráneo y estimular las neuronas corticales. La intensidad y la frecuencia del campo magnético pueden ajustarse para dirigirse a zonas específicas del cerebro y producir efectos excitatorios e inhibitorios. Los principios de la EMT se basan en el concepto de neuroplasticidad, que se refiere a la capacidad del cerebro para cambiar y adaptarse en respuesta a nuevas experiencias y estímulos. Al estimular las neuronas del cerebro con la EMT, es posible inducir cambios en la actividad neuronal y la conectividad, lo que a su vez puede provocar cambios cognitivos y en el estado de ánimo.

Transcranial magnetic stimulation (TMS) is a noninvasive technique that uses magnetic fields to stimulate neurons in the cerebral cortex. While electricity has previously been intended to be used in the medical field, the history of TMS dates back to the discovery of electromagnetic induction by Faraday in the 19th century. However, it was not until the 1980s when Anthony Barker developed the first TMS device at the University of Sheffield. TMS works by means of a coil placed against the scalp, thereby producing a magnetic field. This magnetic field can pass through the skull and stimulate cortical neurons. The intensity and frequency of the magnetic field can be adjusted to target specific areas of the brain and produce excitatory and inhibitory effects. The principles of TMS are based on the concept of neuroplasticity, which refers to the brain's ability to change and adapt in response to new experiences and stimuli. By stimulating neurons in the brain with TMS, it is possible to cause changes in neuronal activity and connectivity, which in turn can lead to cognitive and mood changes.

PTPRN mediates endocytosis of NaV1.2 sodium chan-nels and suppresses epileptogenesis in mice / 中国药理学与毒理学杂志

Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.

Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.@*METHODS@#Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).@*CONCLUSION@#Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Study on after-effect of electroacupuncture with different time intervals on corticospinal excitability in primary motor cortex / 中国针灸

OBJECTIVES@#To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture.@*METHODS@#Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA0 group (received one session of EA), EA6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*).@*RESULTS@#The amplitude of MEPs at T1 and T2 in the EA0 group, at T0* in the EA6h group and at T1, T2 and T3 in the EA48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA0 group and the EA48h group was higher than that in the EA6h group (P<0.001, P<0.01); at T2, it was higher in the EA0 group when compared with that in the EA6h group (P<0.01); at T3, the amplitude in the EA0 group and the EA6h group was lower than that of the EA48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA0 group and the EA48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA6h group (P<0.05); at T2, it was reduced in the EA48h group when compared with that of the EA6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05).@*CONCLUSIONS@#Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.

Dihydroartemisinin Regulates Neuro-microglia to Relieve Neuropathic Pain / 中国实验方剂学杂志

ObjectiveTo evaluate the intervention effect of dihydroartemisinin （DHA） on hippocampal nerve injury in L5 spinal nerve ligation （SNL） model and tumor necrosis factor-α （TNF-α） hippocampal continuous injection model. In primary cultured microglia-hippocampal neurons， the regulatory pattern of DHA on microglia-hippocampal neuronal interactions was confirmed. MethodThe experimental animals were divided into Sham group， SNL group， and DHA group （16 mg·kg-1）， with 3 mice in each group. The hippocampal CA3 glutamatergic neurons were labeled with adeno-associated virus ［Calmodulin-dependent protein kinase Ⅱ（CaMKⅡ） dTomato AAV］， and their contributions to the hippocampal CA1， prefrontal cortex （Frc）， anterior cortex （ACC）， projections of nucleus accumbens （Nac）， and Basolateral Amygdala （BLA） were traced by immunofluorescence staining. The experimental animals were divided into a Sham group， a TNF-α hippocampus continuous injection model group， DHA-L， DHA-M， and DHA-H groups （4， 8， 16 mg·kg-1）， and pregabalin group （25 mg·kg-1）， with 4 mice in each group. The morphology of pyramidal neurons in the hippocampal CA1 and CA3 regions was counted by Golgi staining. The continuous activation of hippocampal primary neurons and microglia was induced， DHA intervention was given by co-culture， and the cell soma area and the expression of postsynaptic density protein 95 （PSD95） inside and outside the primary and secondary dendritic spines of neurons were counted by immunofluorescence. ResultCompared with the Sham group， the projection of CA3 glutamatergic neurons to CA1 region， Frc， and ACC in the SNL group was significantly reduced （P<0.01）， while the projection to Nac and BLA was significantly increased （P<0.01）. As compared with the SNL group， the projection of hippocampal CA3 glutamatergic neurons to CA1 region， Frc， and ACC was significantly increased in the DHA group （P<0.01）， while the projection to Nac and BLA was significantly reduced （P<0.01）. Golgi staining results showed that as compared with the Sham group， the density of dendritic spines and the number of dendritic branches in the CA1 and CA3 pyramidal neurons in the TNF-α hippocampal continuous injection model group were significantly reduced （P<0.01）. As compared with the TNF-α hippocampal continuous injection model， the density of dendritic spines and the number of dendritic branches in hippocampal CA1 and CA3 pyramidal neurons in the DHA-M and DHA-H groups were significantly increased （P<0.05， P<0.01）. Compared with DHA-M group， the total dendrite length of CA1 pyramidal neurons in hippocampus in DHA-H group was significantly increased （P<0.01）， while the total dendrite length of CA1 neurons and the total dendrite base length of CA3 neurons in DHA-L group was significantly decreased （P<0.01）. Compared with the blank control group， the cell soma area of the glycine group and glutamate group increased significantly （P<0.01）. As compared with the glycine group and glutamate group， the cell area of the glycine + glutamate group was significantly increased （P<0.01）， and as compared with the glutamate group， the cell soma area of the glutamate + DHA group was significantly reduced （P<0.01）. As compared with the glycine acid + glutamate group， the cell soma area of the glycine + glutamate + DHA group was significantly reduced （P<0.01）， and as compared with the glutamate + DHA group， the cell soma area of the glycine + glutamate + DHA group was also significantly reduced （P<0.05）. Compared with the blank control group， the cell soma area of the glutamate group was significantly increased （P<0.01）. As compared with the glutamate group， the cell soma area of the glutamate + DHA-L， glutamate + DHA-M， and glutamate + DHA-H groups was significantly reduced （P<0.01）. As compared with the blank control group， the expression of the resting primary microglia + glycine group in primary and secondary dendritic internal and external postsynaptic density protein 95 （PSD95） was significantly increased （P<0.01）. As compared with the resting primary microglia + glycine group， the expression of PSD95 in the primary and secondary dendritic spinous and external neurons of the activated primary microglia + glycine group was significantly reduced （P<0.01）. As compared with the activated primary microglia + glycine group， the expression of PSD95 in the primary and secondary dendritic spinous and external neurons in the activated primary microglia + glycine + DHA group was significantly increased （P<0.01）. As compared with the activated primary microglia + DHA group， the expression of PSD95 in the primary and secondary dendritic spines and outside neurons in the activated primary microglia + glycine + DHA group was significantly increased （P<0.01）. ConclusionDHA has a significant repair effect on vertebral neuronal damage caused by hippocampal microglia and TNF-α overexpression in NP pathology， and this repair is closely related to the dual inhibition of neuronal-microglia by DHA.

Neural Mechanism Underlying Task-Specific Enhancement of Motor Learning by Concurrent Transcranial Direct Current Stimulation / 神经科学通报·英文版

The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm2) during but not before or after the performance of a task. Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS. Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner. Transcranial in vivo Ca2+ imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex (M1). Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance, suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement. Thus, application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.

Effects of repetitive transcranial magnetic stimulation on neuronal excitability and ion channels in hindlimb unloading mice / 生物医学工程学杂志

Weightlessness in the space environment affects astronauts' learning memory and cognitive function. Repetitive transcranial magnetic stimulation has been shown to be effective in improving cognitive dysfunction. In this study, we investigated the effects of repetitive transcranial magnetic stimulation on neural excitability and ion channels in simulated weightlessness mice from a neurophysiological perspective. Young C57 mice were divided into control, hindlimb unloading and magnetic stimulation groups. The mice in the hindlimb unloading and magnetic stimulation groups were treated with hindlimb unloading for 14 days to establish a simulated weightlessness model, while the mice in the magnetic stimulation group were subjected to 14 days of repetitive transcranial magnetic stimulation. Using isolated brain slice patch clamp experiments, the relevant indexes of action potential and the kinetic property changes of voltage-gated sodium and potassium channels were detected to analyze the excitability of neurons and their ion channel mechanisms. The results showed that the behavioral cognitive ability and neuronal excitability of the mice decreased significantly with hindlimb unloading. Repetitive transcranial magnetic stimulation could significantly improve the cognitive impairment and neuroelectrophysiological indexes of the hindlimb unloading mice. Repetitive transcranial magnetic stimulation may change the activation, inactivation and reactivation process of sodium and potassium ion channels by promoting sodium ion outflow and inhibiting potassium ion, and affect the dynamic characteristics of ion channels, so as to enhance the excitability of single neurons and improve the cognitive damage and spatial memory ability of hindlimb unloading mice.

Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal Networks / 神经科学通报·英文版

Acetylcholine (ACh) is an important neuromodulator in various cognitive functions. However, it is unclear how ACh influences neural circuit dynamics by altering cellular properties. Here, we investigated how ACh influences reverberatory activity in cultured neuronal networks. We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses, but to a much lesser extent at high doses. Moreover, high doses of ACh caused a longer duration of evoked reverberation, and a higher occurrence of spontaneous activity. With whole-cell recording from single neurons, we found that ACh inhibited excitatory postsynaptic currents (EPSCs) while elevating neuronal firing in a dose-dependent manner. Furthermore, all ACh-induced cellular and network changes were blocked by muscarinic, but not nicotinic receptor antagonists. With computational modeling, we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations. Thus, ACh modulates network dynamics in a biphasic fashion, probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

Protein Kinase C Controls the Excitability of Cortical Pyramidal Neurons by Regulating Kv2.2 Channel Activity / 神经科学通报·英文版

The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.

Inhibition of intracellular proton-sensitive Ca2+-permeable TRPV3 channels protects against ischemic brain injury

Ischemic brain stroke is pathologically characterized by tissue acidosis, sustained calcium entry and progressive cell death. Previous studies focusing on antagonizing N-methyl-d-aspartate (NMDA) receptors have failed to translate any clinical benefits, suggesting a non-NMDA mechanism involved in the sustained injury after stroke. Here, we report that inhibition of intracellular proton-sensitive Ca2+-permeable transient receptor potential vanilloid 3 (TRPV3) channel protects against cerebral ischemia/reperfusion (I/R) injury. TRPV3 expression is upregulated in mice subjected to cerebral I/R injury. Silencing of TRPV3 reduces intrinsic neuronal excitability, excitatory synaptic transmissions, and also attenuates cerebral I/R injury in mouse model of transient middle cerebral artery occlusion (tMCAO). Conversely, overexpressing or re-expressing TRPV3 increases neuronal excitability, excitatory synaptic transmissions and aggravates cerebral I/R injury. Furthermore, specific inhibition of TRPV3 by natural forsythoside B decreases neural excitability and attenuates cerebral I/R injury. Taken together, our findings for the first time reveal a causative role of neuronal TRPV3 channel in progressive cell death after stroke, and blocking overactive TRPV3 channel may provide therapeutic potential for ischemic brain injury.

Revealing the Precise Role of Calretinin Neurons in Epilepsy: We Are on the Way / 神经科学通报·英文版

Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain. Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons. Calretinin (CR) is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons. The functions of CR and its role in neural excitability are still unknown. Recent data suggest that CR neurons have diverse neurotransmitters, morphologies, distributions, and functions in different brain regions across various species. Notably, CR neurons in the hippocampus, amygdala, neocortex, and thalamus are extremely susceptible to excitotoxicity in the epileptic brain, but the causal relationship is unknown. In this review, we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy. Importantly, we provide perspectives on future investigations of the role of CR neurons in epilepsy.

At the crossroads of epilepsy and sleep: some issues / Na encruzilhada da epilepsia e do sono: algumas questões

There is a close association between sleep and epilepsy, and this literature review aims to raise issues regarding sleep time control, circadian and ultradian rhythms, epilepsy and its interaction with sleep and circadian rhythm, epilepsy and sleep disorders, and finally epilepsy management and medications. It is mentioned that sleep may provide a hypersynchronous state, as occurs in non-rapid eye movement sleep (NREM), and hyperexcitability, in cyclic alternating pattern (CAP), allowing more frequent interictal epileptiform abnormalities and seizures. In some epilepsy syndromes, seizures occur broadly / or entirely during sleep or on awakening, mainly in childhood, and maybe exacerbated in adults during the sleep or sleep-deprived, and there are the so-called Sleep-related epilepsies that are divided as sleep-associated, sleep-accentuated and arousal/awakening related. Sleep quality may be reduced in patients with epilepsy also due to nocturnal seizures or concomitant sleep disorders. Sleep disorders are common in patients with epilepsy and treatment of them mainly sleep-disordered breathing may improve seizure control. Besides, some parasomnias may mimic seizures, and also they can adversely affect the quality and quantity of sleep whereas antiepileptic therapy can have a negative or positive effect on sleep. Nocturnal epileptic seizures may be challenging to discern from parasomnias, in particular NREM parasomnias such as night terrors, sleepwalking and confusional arousals.

Há uma estreita associação entre sono e epilepsia, e esta revisão de literatura tem como objetivo levantar questões relacionadas ao controle do tempo do sono, ritmos circadianos e ultradianos, epilepsia e sua interação com sono e ritmo circadiano, epilepsia e transtornos do sono e, finalmente, o tratamento e medicamentos para epilepsia. Menciona-se que o sono pode proporcionar um estado hipersincrônico, como ocorre no sono "non-rapid eye movement" (NREM), e hiperexcitabilidade, no "cyclic alternating pattern" (CAP), permitindo anormalidades epileptiformes interictais e crises epilépticas mais frequentes. Em algumas síndromes epilépticas, as crises ocorrem ampla / ou inteiramente durante o sono ou despertar, principalmente na infância, e podem ser exacerbadas em adultos durante o sono ou privação de sono, e as chamadas epilepsias relacionadas ao sono se dividem em sono associadas, sono acentuadas e relacionadas com o despertar. A qualidade do sono pode ser reduzida em pacientes com epilepsia também devido a crises epilépticas noturnas ou transtornos do sono concomitantes. Esses são comuns em pacientes com epilepsia e o seu tratamento, principalmente dos transtornos respiratórios do sono, pode melhorar o controle das crises epilépticas. Além disso, algumas parassonias podem mimetizar crises epilépticas, e também elas podem afetar adversamente a qualidade e a quantidade do sono, enquanto a terapia antiepiléptica pode ter um efeito negativo ou positivo sobre o sono. Pode ser difícil discernir as crises epilépticas noturnas das parassonias, em particular das parassonias NREM, como terrores noturnos, crises de sonambulismo e despertares confusionais.

Effect of electroacupuncture combined with motor training on motor learning and motor cortex excitability / 中国针灸

OBJECTIVE@#To compare the effect of electroacupuncture (EA), motor training (MT) and EA combined with MT on motor learning and motor cortex excitability in healthy subjects, and to explore the effect of EA combined with MT on synaptic metaplasticity.@*METHODS@#Using self-control design, 12 healthy subjects were assigned into an EA group, a motor training group (MT group) and an EA plus motor training group (EA+MT group) successively, wash-out period of at least 2 weeks was required between each group. EA was applied at left Hegu (LI 4) in the EA group for 30 min, with continuous wave, 2 Hz in frequency and 0.5-1 mA in density. Motor training of left hand was adopted in the MT group for 30 min. EA and motor training were adopted in the EA+MT group successively. The time of finishing grooved pegboard test (GPT) was observed, and the average amplitude of motor evoked potentials (MEPs), the rest motor threshold (rMT) and the latency were recorded by transcranial magnetic stimulation technique before intervention (T0), after intervention (T1) and 30 min after EA (T3) in the EA group and the EA+MT group, T0 and T1 in the MT group.@*RESULTS@#Compared with T0, the time of finishing GPT was shortened at T1 in the MT group and at T2 in the EA group and the EA+MT group (@*CONCLUSION@#In physiological state, electroacupuncture combined with motor training have a synergistic effect on motor learning, while have no such effect on excitability of cerebral motor cortex.

Hyperpolarization-activated cyclic nucleotide gated cation channels and substances addiction / 中华行为医学与脑科学杂志

Substances addiction is one of the important factors that deeply affect human health.At present, there is still lack of effective treatment drugs in the clinic.Exploring mechanisms of substances addiction, finding new therapeutic targets and developing effective therapeutic drugs are important issues to be solved.Hyperpolarization-activated cyclic nucleotide gated cation channels (HCN channels) participate in many advanced brain activities and are closely related to the occurrence and progression of various brain diseases.Among them, the researches on the role and mechanism of HCN channels in substances addiction are gradually gaining attention.Reviewing the researches regarding substances addiction, abnormal function and abnormal expression of HCN channels were observed in many brain regions under the condition of psychoactive substances addiction.However, it has not yet been able to fully understand the mechanism and the behavioral consequences of this change.Therefore, we review the neurobiological mechanisms of HCN channels in substances addiction induced by opioids, cocaine, cannabis, amphetamines, alcohol and tobacco, in order to provide new ideas for the mechanism researches and treatment of substance addiction.

Mutation in ε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice / 神经科学通报·英文版

Myoclonus dystonia syndrome (MDS) is an inherited movement disorder, and most MDS-related mutations have so far been found in the ε-sarcoglycan (SGCE) coding gene. By generating SGCE-knockout (KO) and human 237 C > T mutation knock-in (KI) mice, we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients. SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro. Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology. Indeed, using a zebrafish MDS model, we found that among 1700 screened chemical compounds, Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models. Our study strengthens the notion that mutations of SGCE lead to MDS and most likely, SGCE functions to brake synaptogenesis in the CNS.

Advance in Neural Control in Eccentric Exercise (review) / 中国康复理论与实践

The nervous system controls eccentric exercise in a special way. During eccentric exercise, excitability increases in cortex, and inhibition decreases, causing excitability decrease in spinal cords. In another hand, increased cortical excitability results in extra excitatory compensation for spinal inhibition. The excitability of the corticospinal pathway depends on the balance between excitability and inhibition of the spinal cord level finally, which usually decreases. Many factors, such as the intensity of contraction, can affect the balance of corticospinal excitability. There is a cross-over effect in eccentric exercise, which promotes corticospinal excitability in untrained limbs. However, the effects and mechanisms of muscle length, fatigue and training duration are still unclear, and current researches have focused in the healthy populations. More researches are needed to explore the effects of eccentric exercise on ill populations.

The efficacy and mechanism of theta burst stimulation for the relief of dysphasia after a stroke / 中华物理医学与康复杂志

Objective:To observe any effect of intermittent theta burst stimulation (iTBS) of the cerebellum on swallowing dysfunction after cerebellar infarction, and to explore its mechanism.Methods:Sixty-two cerebellar stroke survivors with dysphagia were randomly divided into an observation group and a control group, each of 29. In addition to the routine swallowing rehabilitation training, the observation group was treated with iTBS, while the control group was given sham iTBS. The incubation and amplitude of the bilateral suprahyoid muscle motor evoked potential (MEP) were recorded before and after 4 weeks of treatment. The exponential approximate entropy (ApEn) of different brain regions was compared between the two groups during reflex and autonomous swallowing. Swallowing function was evaluated using the penetration-aspiration scale (PAS).Results:MEP incubation in the bilateral suprahyoid muscles had decreased significantly after 4 weeks of treatment in the observation group, and the MEP amplitude in the bilateral suprahyoid muscles of the two groups had increased significantly. The average improvement in the amplitude and incubation in the observation group was significantly greater than in the control group. The average ApEn at C3, C4, P3, P4, T5 and T6 had increased significantly in both groups during both reflex and spontaneous swallowing, with the improvement in the observation group significantly greater. Swallowing function had improved significantly in both groups, but the average PAS grade of the observation group was again significantly better.Conclusions:iTBS can improve the swallowing function of dysphagic cerebellar stroke survivors. This may be due to iTBS improving the excitability of the cerebral cortex and improving motor control of the swallowing muscles.

Correlating cognition and cortical excitability with pain in fibromyalgia: a case control study

Abstract Background: Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal symptoms, primarily attributed to sensitization of somatosensory system carrying pain. Few reports have investigated the impact of fibromyalgia symptoms on cognition, corticomotor excitability, sleepiness, and the sleep quality — all of which can deteriorate the quality of life in fibromyalgia. However, the existing reports are underpowered and have conflicting directions of findings, limiting their generalizability. Therefore, the present study was designed to compare measures of cognition, corticomotor excitability, sleepiness, and sleep quality using standardized instruments in the recruited patients of fibromyalgia with pain-free controls. Methods: Diagnosed cases of fibromyalgia were recruited from the Rheumatology department for the cross-sectional, case-control study. Cognition (Mini-Mental State Examination, Stroop color-word task), corticomotor excitability (Resting motor threshold, Motor evoked potential amplitude), daytime sleepiness (Epworth sleepiness scale), and sleep quality (Pittsburgh sleep quality index) were studied according to the standard procedure. Results: Thirty-four patients of fibromyalgia and 30 pain-free controls were recruited for the study. Patients of fibromyalgia showed decreased cognitive scores (p = 0.05), lowered accuracy in Stroop color-word task (for color: 0.02, for word: 0.01), and prolonged reaction time (< 0.01, < 0.01). Excessive daytime sleepiness in patients were found (< 0.01) and worsened sleep quality (< 0.01) were found. Parameters of corticomotor excitability were comparable between patients of fibromyalgia and pain-free controls. Conclusions: Patients of fibromyalgia made more errors, had significantly increased reaction time for cognitive tasks, marked daytime sleepiness, and impaired quality of sleep. Future treatment strategies may include cognitive deficits and sleep disturbances as an integral part of fibromyalgia management.(AU)

La enfermedad y sus causas en el siglo XIX chileno: La mirada del doctor Guillermo Blest / Disease and its causes in 19th century Chile: Dr. Guillermo Blest's view

Resumen Este artículo analiza el pensamiento médico del doctor Guillermo Blest, expuesto tanto en los informes médicos que envió a las autoridades de gobierno como en un escrito que publicó en 1828 titulado "Ensayo sobre las causas más comunes y activas de las enfermedades que se padecen en Santiago de Chile con indicaciones de los mejores medios para evitar su destructora influencia". En ellos, Blest presenta los principios de irritabilidad (Broussais) y excitabilidad (Brown) como elementos centrales para explicar las causas de las enfermedades. Asimismo, se observa la pervivencia de la teoría miasmática que coexiste con dichos principios explicativos, lo que le permite a Blest configurar un cuadro explicativo de la enfermedad.

Abstract This article aims to analyze the medical thought of Doctor Guillermo Blest, exposed both in the medical reports that he sent to the government authorities and in a document that he published in 1828 entitled "Assay on the most common and active causes of the diseases that are suffered in Santiago de Chile with indications of the best means to avoid its destructive influence". In them, Blest presents the principles of irritability (Broussais) and excitability (Brown) as central elements to explain the causes of diseases. Likewise, the miasmatic theory coexists with these explanatory principles, allowing Blest to configure an explanatory panorama of the disease.