Modulation of Neural Circuits in Crustacea

Recent research has shown that neuromodulators play importantroles in shaping simple behaviors. They act at many differentsites within the animal in a coordinated fashion, modulatingthe motor circuits in the central nervous system, altering motoneuronexcitability, and modulating muscle response to motoneuron input.Within the central circuits that co-ordinate simple movements,neuromodulators play a dramatic sculpting role, changing thecells that participate in the circuit, altering their intrinsicproperties, and affecting the strength of synaptic interactionsthat form the "wiring diagram" of the circuit. As a result,they are able to shape a family of related circuits out of asingle anatomically identified network, each driving a uniquevariant on the basic motor theme. Examples of these actionsfrom the Crustacea are described in this paper, focussing onthe modulation of posture in the lobster, and on modulationof rhythmic motor programs for stomach movements in the stomatogastricganglion of lobsters and crabs.     

Modulation of Inhibitory Synaptic Transmission in the Cat Motor Cortex Related to Realization of an Operant Reflex Evoked by a Complex of Stimuli

In non-anesthetized cats, we examined the effects of iontophoretic microinjections of GABA, a blocker of GABAergic synaptic transmission, and modulators of noradrenergic transmission on impulse activity (IA) generated by motor cortex neurons in the course of realization of an operant motor reflex to the action of a complex of stimuli (warning and imperative ones). We tried to elucidate the role of different membrane receptors in modulation of spiking of cortical neurons. Microiontophoretic applications of GABA and noradrenaline resulted in decreases in the frequency of background IA of cortical neurons and suppression of their reactions related to realization of the operant reflex. The use of selective adrenoactive substances showed that applications of an α1 agonist, Mezaton, suppressed background spiking and impulsation generated within an interspike interval and in the course of the movement. An α2 blocker, yohimbine, exerted an opposite effect; the neuronal IA was intensified within the background period and other examined time intervals. There are reasons to believe that noradrenergic modulation of IA of cortical neurons is realized via direct effects on pyramidal neurons and also indirectly, through changes in the activity of inhibitory cortical interneurons.     

Mixed Signal Learning by Spike Correlation Propagation in Feedback Inhibitory Circuits

The brain can learn and detect mixed input signals masked by various types of noise, and spike-timing-dependent plasticity (STDP) is the candidate synaptic level mechanism. Because sensory inputs typically have spike correlation, and local circuits have dense feedback connections, input spikes cause the propagation of spike correlation in lateral circuits; however, it is largely unknown how this secondary correlation generated by lateral circuits influences learning processes through STDP, or whether it is beneficial to achieve efficient spike-based learning from uncertain stimuli. To explore the answers to these questions, we construct models of feedforward networks with lateral inhibitory circuits and study how propagated correlation influences STDP learning, and what kind of learning algorithm such circuits achieve. We derive analytical conditions at which neurons detect minor signals with STDP, and show that depending on the origin of the noise, different correlation timescales are useful for learning. In particular, we show that non-precise spike correlation is beneficial for learning in the presence of cross-talk noise. We also show that by considering excitatory and inhibitory STDP at lateral connections, the circuit can acquire a lateral structure optimal for signal detection. In addition, we demonstrate that the model performs blind source separation in a manner similar to the sequential sampling approximation of the Bayesian independent component analysis algorithm. Our results provide a basic understanding of STDP learning in feedback circuits by integrating analyses from both dynamical systems and information theory.     

Differential Modulation of Corticospinal Excitability by Different Current Densities of Anodal Transcranial Direct Current Stimulation

Background

Novel non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have been developed in recent years. TDCS-induced corticospinal excitability changes depend on two important factors current intensity and stimulation duration. Despite clinical success with existing tDCS parameters, optimal protocols are still not entirely set.

Objective/hypothesis

The current study aimed to investigate the effects of four different anodal tDCS (a-tDCS) current densities on corticospinal excitability.

Methods

Four current intensities of 0.3, 0.7, 1.4 and 2 mA resulting in current densities (CDs) of 0.013, 0.029, 0.058 and 0.083 mA/cm² were applied on twelve right-handed (mean age 34.5±10.32 yrs) healthy individuals in different sessions at least 48 hours apart. a-tDCS was applied continuously for 10 minute, with constant active and reference electrode sizes of 24 and 35 cm² respectively. The corticospinal excitability of the extensor carpi radialis muscle (ECR) was measured before and immediately after the intervention and at 10, 20 and 30 minutes thereafter.

Results

Post hoc comparisons showed significant differences in corticospinal excitability changes for CDs of 0.013 mA/cm² and 0.029 mA/cm² (P = 0.003). There were no significant differences between excitability changes for the 0.013 mA/cm² and 0.058 mA/cm² (P = 0.080) or 0.013 mA/cm² and 0.083 mA/cm² (P = 0.484) conditions.

Conclusion

This study found that a-tDCS with a current density of 0.013 mA/cm² induces significantly larger corticospinal excitability changes than CDs of 0.029 mA/cm². The implication is that might help to avoid applying unwanted amount of current to the cortical areas.     

苦参碱对哇巴因诱导钠电流改变的调节作用

目的:探讨苦参碱拮抗哇巴因诱导的心律失常的作用机制。方法:应用全细胞膜片钳技术记录哇巴因对单个豚鼠心室肌细胞的Na+电流和动作电位时程作用后,观察苦参碱对哇巴因诱导Na+电流和动作电位时程改变的恢复作用。结果:1 5μmol·L-1哇巴因延长APD50从给药前476±40.7 ms增加到744±62.9 ms(n=6,P0.05),APD90从给药前499±84.9 ms增加到775±87.7 ms(n=6,P0.01),100μmol·L-1苦参碱恢复APD50至603±79.0 ms(n=6,P0.05),APD90至630±81.6 ms(n=6,P0.05);2 5μmol·L-1哇巴因可增加钠电流的峰值,在-20 m V电压条件下,5μmol·L-1哇巴因增加INa,由正常-40.9±2.32 p A/p F增加到-55.2±2.26 p A/p F(n=8,P0.05),100μmol·L-1苦参碱减少INa至-34.6±2.14 p A/p F(n=8,P0.05);5μmol·L-1哇巴因右移钠通道的激活曲线,并左移钠通道的失活曲线从而改变通道动力学特性;100μmol·L-1苦参碱可抑制哇巴因诱导的INa的增加,并恢复Na+通道动力学特性接近正常。结论:苦参碱拮抗哇巴因诱导的心律失常机制与其抑制哇巴因诱发细胞水平Na+电流的增加,缩短哇巴因诱发APD的延长有关。     

Excitability Changes in Intracortical Neural Circuits Induced by Differentially Controlled Walking Patterns

Our previous single-pulse transcranial magnetic stimulation (TMS) study revealed that excitability in the motor cortex can be altered by conscious control of walking relative to less conscious normal walking. However, substantial elements and underlying mechanisms for inducing walking-related cortical plasticity are still unknown. Hence, in this study we aimed to examine the characteristics of electromyographic (EMG) recordings obtained during different walking conditions, namely, symmetrical walking (SW), asymmetrical walking 1 (AW1), and asymmetrical walking 2 (AW2), with left to right stance duration ratios of 1:1, 1:2, and 2:1, respectively. Furthermore, we investigated the influence of three types of walking control on subsequent changes in the intracortical neural circuits. Prior to each type of 7-min walking task, EMG analyses of the left tibialis anterior (TA) and soleus (SOL) muscles during walking were performed following approximately 3 min of preparative walking. Paired-pulse TMS was used to measure short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in the left TA and SOL at baseline, immediately after the 7-min walking task, and 30 min post-task. EMG activity in the TA was significantly increased during AW1 and AW2 compared to during SW, whereas a significant difference in EMG activity of the SOL was observed only between AW1 and AW2. As for intracortical excitability, there was a significant alteration in SICI in the TA between SW and AW1, but not between SW and AW2. For the same amount of walking exercise, we found that the different methods used to control walking patterns induced different excitability changes in SICI. Our research shows that activation patterns associated with controlled leg muscles can alter post-exercise excitability in intracortical circuits. Therefore, how leg muscles are activated in a clinical setting could influence the outcome of walking in patients with stroke.     

Able-Bodied Wild Chimpanzees Imitate a Motor Procedure Used by a Disabled Individual to Overcome Handicap

Chimpanzee culture has generated intense recent interest, fueled by the technical complexity of chimpanzee tool-using traditions; yet it is seriously doubted whether chimpanzees are able to learn motor procedures by imitation under natural conditions. Here we take advantage of an unusual chimpanzee population as a ‘natural experiment’ to identify evidence for imitative learning of this kind in wild chimpanzees. The Sonso chimpanzee community has suffered from high levels of snare injury and now has several manually disabled members. Adult male Tinka, with near-total paralysis of both hands, compensates inability to scratch his back manually by employing a distinctive technique of holding a growing liana taut while making side-to-side body movements against it. We found that seven able-bodied young chimpanzees also used this ‘liana-scratch’ technique, although they had no need to. The distribution of the liana-scratch technique was statistically associated with individuals'' range overlap with Tinka and the extent of time they spent in parties with him, confirming that the technique is acquired by social learning. The motivation for able-bodied chimpanzees copying his variant is unknown, but the fact that they do is evidence that the imitative learning of motor procedures from others is a natural trait of wild chimpanzees.     

Modulation of Apoptosis Induced by Tricyclic Antidepressants in Human Peripheral Lymphocytes

We have recently reported that the tricyclic antidepressants (TCAs) imipramine, clomipramine, and citalopram induce apoptosis in human peripheral lymphocytes. This system is well suited for studies on the pathophysiology/physiology of apoptosis regulation. Apoptosis was determined using both DNA gel electrophoresis and flow cytometric analysis. TCA-induced apoptosis in lymphocytes was monitored in the presence of the protein synthesis inhibitor cycloheximide (CHX), the RNA synthesis inhibitor actinomycin D (Act D), the antioxidant reduced glutathione (GSH), the nuclease inhibitor aurintricarboxylic acid (ATA), the cytokine interlukin-2 (IL-2), and the immunostimulator linomide. CHX and Act D failed to prevent and actually enhanced TCA-induced apoptosis in lymphocytes, indicating that protein and RNA syntheses are not required for this process. Exogenous IL-2, GSH, and ATA protected the lymphocytes from apoptosis induced by TCAs in a dose-dependent manner, whereas linomide had no effect on TCA-induced apoptosis under our in vitro conditions. Our data demonstrate that TCA-induced apoptosis in human lymphocytes shares many common features with other stimuli-induced apoptotic processes. © 1997 John Wiley & Sons, Inc. J Biochem Toxicol 12: 115–123, 1998     

The Supplementary Motor Area Exerts a Tonic Excitatory Influence on Corticospinal Projections to Phrenic Motoneurons in Awake Humans

Introduction

In humans, cortical mechanisms can interfere with autonomic breathing. Respiratory-related activation of the supplementary motor area (SMA) has been documented during voluntary breathing and in response to inspiratory constraints. The SMA could therefore participate in the increased resting state of the respiratory motor system during wake (i.e. "wakefulness drive to breathe").

Methods

The SMA was conditioned by continuous theta burst magnetic stimulation (cTBS, inhibitory) and 5 Hz conventional rTMS (5 Hz, excitatory). The ensuing effects were described in terms of the diaphragm motor evoked response (DiMEPs) to single-pulse transcranial magnetic stimulation over the motor cortex. DiMEPs were recorded at baseline, and at 3 time-points ("post1", "post2", "post3") up to 15 minutes following conditioning of the SMA.

Results

cTBS reduced the amplitude of DiMEPs from 327.5±159.8 µV at baseline to 243.3±118.7 µV, 217.8±102.9 µV and 240.6±123.9 µV at post 1, post 2 and post 3, respectively (F = 6.341, p = 0.002). 5 Hz conditioning increased the amplitude of DiMEPs from 184.7±96.5 µV at baseline to 270.7±135.4 µV at post 3 (F = 4.844, p = 0.009).

Conclusions

The corticospinal pathway to the diaphragm can be modulated in both directions by conditioning the SMA. This suggests that the baseline respiratory activity of the SMA represents an equipoise from which it is possible to move in either direction. The resting corticofugal outflow from the SMA to phrenic motoneurones that this study evidences could putatively contribute to the wakefulness drive to breathe.     

Attention-Dependent Modulation of Cortical Taste Circuits Revealed by Granger Causality with Signal-Dependent Noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention.     

Functional Motor Recovery from Motoneuron Axotomy Is Compromised in Mice with Defective Corticospinal Projections

Brachial plexus injury (BPI) and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST) is genetically absent. In adult mice, we tore off right C5–C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP) in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs) and reduced peak-to-peak amplitudes in electromyogram (EMG), than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI.     

Functional Corticospinal Projections from Human Supplementary Motor Area Revealed by Corticomuscular Coherence during Precise Grip Force Control

The purpose of the present study was to investigate whether corticospinal projections from human supplementary motor area (SMA) are functional during precise force control with the precision grip (thumb-index opposition). Since beta band corticomuscular coherence (CMC) is well-accepted to reflect efferent corticospinal transmission, we analyzed the beta band CMC obtained with simultaneous recording of electroencephalographic (EEG) and electromyographic (EMG) signals. Subjects performed a bimanual precise visuomotor force tracking task by applying isometric low grip forces with their right hand precision grip on a custom device with strain gauges. Concurrently, they held the device with their left hand precision grip, producing similar grip forces but without any precision constraints, to relieve the right hand. Some subjects also participated in a unimanual control condition in which they performed the task with only the right hand precision grip while the device was held by a mechanical grip. We analyzed whole scalp topographies of beta band CMC between 64 EEG channels and 4 EMG intrinsic hand muscles, 2 for each hand. To compare the different topographies, we performed non-parametric statistical tests based on spatio-spectral clustering. For the right hand, we obtained significant beta band CMC over the contralateral M1 region as well as over the SMA region during static force contraction periods. For the left hand, however, beta band CMC was only found over the contralateral M1. By comparing unimanual and bimanual conditions for right hand muscles, no significant difference was found on beta band CMC over M1 and SMA. We conclude that the beta band CMC found over SMA for right hand muscles results from the precision constraints and not from the bimanual aspect of the task. The result of the present study strongly suggests that the corticospinal projections from human SMA become functional when high precision force control is required.     

亚慢性砷中毒对大鼠肝脏自噬的抑制作用

目的:在建立亚慢性砷暴露模型的基础上,探讨砷暴露对SD大鼠肝脏自噬水平的影响.方法:出生21天断乳雄性SD大鼠分为不同水平砷暴露组,通过饮水给与NaAsO2的方式染毒;全自动生化分析仪检测血清肝功能项目的变化;HE染色检测肝脏组织病理学改变;透射电镜法超微结构的改变.Western blot方法检测自噬相关蛋白Beclin1、LC3表达水平变化.结果:砷暴露组肝脏出现显著的异常,同时伴随肝组织形态学改变.于是此同时,LC3Ⅱ/LC3Ⅰ比值以及beclin1的表达水平均随着砷作用浓度的升高而降低.结论:亚慢性砷暴露在诱导肝脏损伤的同时可伴随自噬水平的抑制,这种水平的改变可能参与了砷的肝脏毒性.     

Modulation of Brain Activity during a Stroop Inhibitory Task by the Kind of Cognitive Control Required

This study used a proportion congruency manipulation in the Stroop task in order to investigate, at the behavioral and brain substrate levels, the predictions derived from the Dual Mechanisms of Control (DMC) account of two distinct modes of cognitive control depending on the task context. Three experimental conditions were created that varied the proportion congruency: mostly incongruent (MI), mostly congruent (MC), and mostly neutral (MN) contexts. A reactive control strategy, which corresponds to transient interference resolution processes after conflict detection, was expected for the rare conflicting stimuli in the MC context, and a proactive strategy, characterized by a sustained task-relevant focus prior to the occurrence of conflict, was expected in the MI context. Results at the behavioral level supported the proactive/reactive distinction, with the replication of the classic proportion congruent effect (i.e., less interference and facilitation effects in the MI context). fMRI data only partially supported our predictions. Whereas reactive control for incongruent trials in the MC context engaged the expected fronto-parietal network including dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex, proactive control in the MI context was not associated with any sustained lateral prefrontal cortex activations, contrary to our hypothesis. Surprisingly, incongruent trials in the MI context elicited transient activation in common with incongruent trials in the MC context, especially in DLPFC, superior parietal lobe, and insula. This lack of sustained activity in MI is discussed in reference to the possible involvement of item-specific rather than list-wide mechanisms of control in the implementation of a high task-relevant focus.     

Modulation of Coordinated Activity across Cortical Layers by Plasticity of Inhibitory Synapses

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Modulation of Motor Area Activity by the Outcome for a Player during Observation of a Baseball Game

Background

Observing competitive games such as sports is a pervasive entertainment among humans. The inclination to watch others play may be based on our social-cognitive ability to understand the internal states of others. The mirror neuron system, which is activated when a subject observes the actions of others, as well as when they perform the same action themselves, seems to play a crucial role in this process. Our previous study showed that activity of the mirror neuron system was modulated by the outcome of the subject''s favored player during observation of a simple competitive game (rock-paper-scissors). However, whether the mirror neuron system responds similarly in a more complex and naturalistic sports game has not yet been fully investigated.

Methodology/Principal Findings

In the present study, we measured the activity of motor areas when the subjects, who were amateur baseball field players (non-pitchers), watched short movie clips of scenes in professional baseball games. The subjects were instructed to support either a batter or a pitcher when observing the movie clip. The results showed that activity in the motor area exhibited a strong interaction between the subject''s supported side (batter or pitcher) and the outcome (a hit or an out). When the subject supported the batter, motor area activity was significantly higher when the batter made an out than when he made a hit. However, such modulation was not apparent when the subject supported the pitcher.

Conclusions/Significance

This result indicates that mirror neuron system activity is modulated by the outcome for a particular player in a competitive game even when observing a complex and naturalistic sports game. We suggest that our inclination to watch competitive games is facilitated by this characteristic of the mirror neuron system.     

Developmental Changes in Task‐Induced Brain Deactivation in Humans Revealed by a Motor Task

Performing tasks activates relevant brain regions in adults while deactivating task‐irrelevant regions. Here, using a well‐controlled motor task, we explored how deactivation is shaped during typical human development and whether deactivation is related to task performance. Healthy right‐handed children (8–11 years), adolescents (12–15 years), and young adults (20–24 years; 20 per group) underwent functional magnetic resonance imaging with their eyes closed while performing a repetitive button‐press task with their right index finger in synchronization with a 1‐Hz sound. Deactivation in the ipsilateral sensorimotor cortex (SM1), bilateral visual and auditory (cross‐modal) areas, and bilateral default mode network (DMN) progressed with development. Specifically, ipsilateral SM1 and lateral occipital deactivation progressed prominently between childhood and adolescence, while medial occipital (including primary visual) and DMN deactivation progressed from adolescence to adulthood. In adults, greater cross‐modal deactivation in the bilateral primary visual cortices was associated with higher button‐press timing accuracy relative to the sound. The region‐specific deactivation progression in a developmental period may underlie the gradual promotion of sensorimotor function segregation required in the task. Task‐induced deactivation might have physiological significance regarding suppressed activity in task‐irrelevant regions. Furthermore, cross‐modal deactivation develops to benefit some aspects of task performance in adults.     

Inhibitory Modulation by Sodium Ions of the N-Methyl-D-Aspartate Recognition Site in Brain Synaptic Membranes

Specific binding of radiolabeled L-glutamic acid (Glu) was examined using rat brain synaptic membranes treated with a low concentration of Triton X-100. The binding drastically increased in proportion to increasing concentrations of the detergent used up to 0.1%. Addition of 100 mM sodium acetate significantly potentiated the binding in membranes not treated with Triton X-100, whereas it markedly inhibited the binding in Triton-treated membranes. The binding in Triton-treated membranes was inversely dependent on incubation temperature and reached a plateau within 10 min after the initiation of incubation at 2 degrees C, whereas the time required to attain equilibrium at 30 degrees C was less than 1 min. Sodium acetate invariably inhibited the binding detected at both temperatures independently of the incubation time via decreasing the affinity for the ligand. The binding was significantly displaced by agonists and antagonists for an N-methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors, but not by those for the other subclasses. Inclusion of sodium acetate reduced the potencies of NMDA agonists to displace the binding without virtually affecting those of NMDA antagonists. Moreover, sodium ions inhibited the ability of Glu to potentiate the binding of N-[3H] [1-(2-thienyl)cyclohexyl]piperidine to open NMDA channels in Triton-treated membranes. These results suggest that sodium ions may play an additional modulatory role in the termination process of neurotransmission mediated by excitatory amino acids via facilitating a transformation of the NMDA recognition site from a state with high affinity for agonists to a state with low affinity.