Reciprocal Inhibition Research Articles

Reciprocal inhibition between motor neurons of the tibialis anterior and triceps surae in humans.

Motor neurons innervating antagonist muscles receive reciprocal inhibitory afferent inputs to facilitate the joint movement in the two directions. The present study investigates the mutual transmission of reciprocal inhibitory afferent inputs between the tibialis anterior (TA) and triceps surae (soleus and medial gastrocnemius) motor units. We assessed this mutual mechanism in large populations of motor units for building a statistical distribution of the inhibition amplitudes during standardized input to the motor neuron pools to minimize the effect of modulatory pathways. Single motor unit activities were identified using high-density surface electromyography (HDsEMG) recorded from the TA, soleus (Sol), and medial gastrocnemius (GM) muscles during isometric dorsi- and plantarflexion. Reciprocal inhibition on the antagonist muscle was elicited by electrical stimulation of the tibial (TN) or common peroneal nerves (CPN). The probability density distributions of reflex strength for each muscle were estimated to examine the strength of mutual transmission of reciprocal inhibitory input. The results showed that the strength of reciprocal inhibition in the TA motor units was fourfold greater than for the GM and the Sol motor units. This suggests an asymmetric transmission of reciprocal inhibition between ankle extensor and flexor muscles. This asymmetry cannot be explained by differences in motor unit type composition between the investigated muscles since we sampled low-threshold motor units in all cases. Therefore, the differences observed for the strength of inhibition are presumably due to a differential reciprocal spindle afferent input and the relative contribution of nonreciprocal inhibitory pathways. NEW & NOTEWORTHY We investigated the mutual transmission of reciprocal inhibition in large samples of motor units using a standardized input (electrical stimulation) to the motor neurons. The results demonstrated that the disynaptic reciprocal inhibition exerted between ankle flexor and extensor muscles is asymmetric. The functional implication of asymmetric transmission may be associated with the neural strategies of postural control.

F143 Systemic assessment of motor pathophysiology of corticobasal syndrome

Introduction Corticobasal syndrome (CBS) is a kind of tauopathy with parkinsonism presenting chronic onset of progressive unilateral motor impairment, including subjective weakness, dystonia and parkinsonism, and cognition change, such as apraxia, sensory-motor dysfunction or memory impairment. Although several types of pathophysiology have been reported on CBS, a systemic physiological study on CBS has been lacking. Seeing the symptoms of CBS is a mixture of parkinsonism and other movement disorders, e.g. dystonia, we designed this study to investigate a wide range of motor physiology, including different forms of plasticity, the connection between the premotor cortex (PMd) and M1, and inhibitory circuits in the cortex, brainstem and spinal cord, in patients with CBS. Methods We rolled in 21 patients with CBS diagnosed by Cambridge criteria and age-matched health subjects. All subjects signed informed consent under supervision of approval of the Ethics Board of Chang Gung Memorial Hospital at Linkou. Studied protocols included (1) Motor LTP-like plasticity by cTBSc0: cTBS followed by 1-min slightly voluntary contraction of the contralateral FDI muscle, (2) SICI recruitment curve before and after cTBSc0, (3) depotentiation assessed by cTBSc0 and subsequent 10 s of cTBS (cTBS150), (4) brainstem blink reflex recovery cycle (BR), (5) spinal reciprocal inhibition (RI), and (6) PMd-M1 connectivity by assessing M1 excitability change in response to cTBS given to PMd. Results Although cTBSc0 successfully induced LTP, depotentiation was abnormal in patients with CBS. The SICI recruitment curve shifted to the left as compared to the controls in the baseline, and was moved toward to normal after cTBSc0. The blink reflex recovery curve was identical between CBS patients and healthy controls. RI showed reduced 3rd phase and normal 1st and 2nd phases, and the PMd-M1 connectivity was abnormal in patients with CBS. Conclusion Different from a previous study showing reduced LTP using iTBS, the current study revealed normal motor plasticity in CBS. Similar results were also found in PD patient at the medication ON state, in which cTBSc0, but not iTBS, was able to induce motor plasticity. The abnormal depotentiation in CBS who has not dyskinesia is different from that in PD patients and could be closer to the pathophysiology of dystonia. Abnormal SICI, which was normalized by cTBSc0, abnormal the third, but not other, phase(s) of RI and normal blink reflex recovery curve suggest the pathophysiology is mainly located in the cerebrum, while the brainstem and spinal cord are preserved. The abnormal PMd-M1 connectivity may be unspecific and has been also seen in both PD and dystonia. In summary, patients with CBS show unique presentation in a combination of different physiological assessments, suggesting the possibility of development of physiological biomarker for CBS. Moreover, rTMS over M1 may improve CBS according to the results in SICI.

T80. Alteration of intermuscular coherence in synergistic muscle pairs during actual elbow flexion contractions after cervical spinal cord injury

Introduction During isometric contractions, the level of antagonist muscles activation is increased in people with cervical spinal cord injury (cSCI) in comparison to healthy participants. This alteration of antagonists activation after cSCI has been primarily associated with a lower cortical control of the spinal mechanisms – especially reciprocal inhibition – regulating agonists-antagonists co-activation. Through time-frequency intermuscular coherence analysis, which is likely to reflect the strength of the common neural drive across multiple muscles, this study investigates the influence of a cSCI on the common neural drive regulating the activity of agonist and antagonist muscles pairs. Methods The EMG of elbow flexors (biceps brachii, brachioradialis) and elbow extensors (long and short heads of the triceps brachii) was recorded while 8 participants with cSCI (SCI group) and 10 able-bodied participants (AB group) performed 21 isometric 6-s elbow isometric flexion contractions at 3 force levels (20%, 40% and 60% of MVC). The magnitude of intermuscular coherence between the EMG signals from elbow flexors (AGO-AGO), elbow extensors (ANTAGO-ANTAGO) and all possible pairs of elbow flexors-extensors (AGO-ANTAGO) was quantified in alpha (8–12 Hz), beta (15–30 Hz) and gamma (35–60 Hz) frequency bands. The magnitude of the intermuscular coherence and the mean net joint torque produced around the elbow joint were analyzed over a 2-s stable force production window for all contractions. The effects of the Force level and Group were tested using adequate statistical tests according to the distribution of the dependent variables. Results Results revealed that the net joint torque significantly increased with the Force level in both groups with no significant Group difference. In the beta-band, AGO-ANTAGO intermuscular coherence magnitude was significantly lower in the SCI group than in the AB group. In the gamma-band, the ANTAGO-ANTAGO intermuscular coherence magnitude significantly increased concomitantly with the Force level in both groups. No significant intermuscular coherence was found in the alpha-band, whatever the group and the muscle pair. Conclusion The alteration of AGO-ANTAGO intermuscular coherence magnitude in the beta-band after cSCI could reflect reduced common neural drive influencing the spinal inhibitory mechanisms. This finding may suggest lower common drive to agonist-antagonist muscle pairs in SCI participants, which could take part in the alteration of antagonist muscles co-activation. Increased ANTAGO-ANTAGO coherence magnitude with the force level revealed in the gamma-band could be related to the Piper rhythm phenomenon, which contributes to synchronize muscle activations to gain in efficiency, especially at high force levels. Despite lower intermuscular coupling between agonist and antagonist muscles, our results taken together support that the central mechanisms controlling the modulation of the force level are preserved during actual contractions after cSCI.

F189. Reciprocal excitation: A hidden component of the myotatic stretch reflex

Introduction The Myotatic Reflex (MR) and Reciprocal Inhibition (RI) are well documented phenomena. They fit well into the framework of negative feedback control of muscle length and complementary control of movement by opposite groups of muscles. Reciprocal excitation (RE) has been reported intermittently and controversially, only in patients with spasticity of various forms. While using quantitative measures of the MR, we recorded clear and consistent electrical evidence of RE in normal subjects. Our experiments show that the standard textbook model of the MR is in fact incomplete. In this paper we present experimental evidence confirming the presence of RE as a spinal reflex, in normal subjects. Methods Three methods were used to elicit the MR of the quadriceps muscle: the patellar tendon tap, rapid mechanical flexion at the knee, electrical stimulation of the femoral nerve. The electrical response from the agonist and antagonist muscles were recorded simultaneously using surface EMG. Following the stretch of the quadriceps, the reflex excitation from the quadriceps and a smaller excitation from the hamstrings was recorded. Mechanical artefacts and cross-pickup from neighbouring muscles were excluded. Data from 28 normal subjects was processed and analysed with custom programs in Python. The mechanical stretch stimulus was the flexion at the knee lasting roughly 100 ms making it difficult to identify a single time-point of stretch stimulus. On electrical stimulation of the femoral nerve in the femoral triangle it was difficult to separate the reflex wave from the stimulation artefact as most subjects required strong stimulus. Results Excitation of the heteronymous group of muscles as a component of the MR in normal subjects has been clearly observed in our experiments. Though this excitation is around 10% of the primary reflex excitation, its latency and reproducibility confirm its physiological origin as a spinal reflex. The patellar tendon tap latency(ms) and amplitude(mV) ranges averaged over 25 trials for each of the 28 subjects, seen distinct from background noise are, respectively: Rectusfemoris = 15–22, 0.0473–2.1503; Bicepsfemoris = 17–33, 0.0076–0.3462, Semitendinosus = 17–33, 0.003–0.2015. The recordings with mechanical stretch and electrical stimulation of the femoral nerve confirm distinct RE in the hamstrings. Conclusion There are a few reports of RE in spasticity. We have demonstrated its presence in normal subjects. The coexcitation of the antagonist at the same time as the agonist may play an important role in providing stability around a joint to prevent injuries when there is rapid stretch of the agonist. Our data suggests that further studies are required to understand its neuronal pathway, relevance and potential clinical use in normal subjects and pathology.

Mutual suppression of miR-125a and Lin28b in human hepatocellular carcinoma cells

MicroRNA-125a exhibits an antiproliferative activity and is downregulated in several types of tumors, including hepatocellular carcinoma where it targets sirtuin-7, matrix metalloproteinase-11, and c-Raf. Another target of miR-125a is Lin28, a pluripotency factor that is generally undetectable in differentiated cells but is often upregulated/reactivated in tumors where it acts as an oncogenic factor promoting cell proliferation and tumor progression. In this study we show that downregulation of Lin28b by miR-125a partially accounts for its antiproliferative activity toward hepatocellular carcinoma cells. We also found that Lin28b is able to bind a conserved GGAG motif of pre-miR-125a and to inhibit its maturation in hepatocellular carcinoma cells. Reciprocal inhibition between miR-125a and Lin28b reasonably generates a positive feedback loop where reactivation of Lin-28b inhibits the expression of both miR-125a and let-7, reinforcing its own expression and leading to a marked overexpression of the mitogenic targets of the two miRNAs. On the other hand, perturbation of these circuits by overexpression of miR-125a suppresses Lin28b leading to a decreased cell proliferation. Overall, these data support a tumor suppressive role for miR-125a and contribute to the elucidation of its molecular targets.

Effects of wrist position on reciprocal inhibition and cutaneous reflex amplitudes in forearm muscles

In the leg, amplitudes of cutaneous reflexes and reciprocal inhibition are significantly affected by joint and limb position. Comparatively little is known about such modulation in the arm. In this study, amplitudes of reciprocal inhibition (from median nerve stimulation near elbow) and cutaneous reflexes (from median or superficial radial nerve stimulation at the wrist) were measured in forearm muscle extensor carpi radialis with the hand pronated or neutral during graded voluntary activation. Significant correlations with muscle activation were found for reciprocal inhibition and cutaneous reflex amplitudes at both positions. Only cutaneous reflexes from superficial radial nerve were modulated by wrist position. This study reveals that effect of limb position is nerve-specific in cutaneous reflexes and not significant on reciprocal inhibition in the arm. This has implications for measurement and study design in those who have mobility and motor activation challenges (e.g. neurotrauma) that affect hand function.

A tetravalent vaccine comprising hexon-chimeric adenoviruses elicits balanced protective immunity against human adenovirus types 3, 7, 14 and 55

Human adenovirus (Ad) species B contains several of the most important types associated with acute respiratory diseases, Ad3, -7, -14 and -55, which often lead to severe lower respiratory tract diseases and epidemic outbreaks. However, there is currently no Ad vaccine approved for general use. The major capsid protein, hexon, is the primary determinant recognized by neutralizing antibodies (NAbs). In this study, four recombinant Ads that have the same genome sequence as Ad3 with the exception of the hexon genes, rAd3EGFP, rAd3H7, rAd3H14 and rAd3H55, were combined as a tetravalent Ad candidate vaccine against Ad3, -7, -14 and -55. The replication efficiencies of chimeric rAd3H14, rAd3H7 and rAd3H55 were similar to that of rAd3EGFP. Recombinant rAd3EGFP, rAd3H7, rAd3H14 and rAd3H55 induced high titers of NAbs against Ad3, -7, -14 and -55, respectively, which were comparable to those induced by wild-type Ads. The mixture of the four recombinant Ads in equal proportions, rAdMix, or rAdMix inactivated by β-propiolactone, induced balanced NAb responses against Ad3, -7, -14 and -55 in mice without reciprocal immunological interference. In co-culture the four recombinant Ads replicated with a similar efficiency without reciprocal inhibition, and the progeny virions may be chimeric. Purified co-culture, rAdMix-C, also elicited balanced immune responses, suggesting a simple method for multivalent vaccine production. These results indicate the possible advantage of the four Ads as a live combined vaccine. Importantly, pre-immunization with rAdMix conferred protection against Ad3, -7, -14 or -55 challenge in mice in vivo. Thus, this research provides a novel tetravalent Ad vaccine candidate against Ad3, -7, -14 and -55.

Dishevelled has YAP nuclear export function in a tumour suppressor context dependent manner

The Hippo signaling is an evolutionary conserved pathway that inhibits cell proliferation by contact inhibition, and whose loss leads to organ growth and cancer development. The Yes‐associated protein (YAP) transcription co‐activator is a key regulator of the Hippo pathway. Phosphorylation‐dependent YAP translocation is a well‐known intracellular mechanism of the Hippo pathway, however the responsible molecular effectors by which the YAP leads cytosolic translocation remain undefined. Recent findings indicate that oncogenic YAP paradoxically suppresses canonical Wnt activity.We found that DVL, a scaffolding protein of the Wnt pathway as well as a key regulator of Wnt‐independent epithelial polarity, is a molecular effector for nuclear‐cytoplasmic shuttling of YAP in a YAP‐phosphorylation dependent manner. Mutational inactivation of the nuclear export signal in DVL leads to nuclear YAP retention, with increases TEAD transcriptional activity. DVL is also required for YAP intracellular dynamics induced by E‐cadherin, α‐catenin, or AMPK activation. Importantly, the nuclear‐cytoplasmic trafficking is largely dependent on the p53‐Lats2 or LKB1‐AMPK tumor suppressor axes, which determine YAP phosphorylation status. Conversely, loss of p53 or LKB1 relieves DVL‐linked reciprocal inhibition between the canonical Wnt pathway and nuclear YAP activity. Our observations provide novel mechanistic insights into controlled proliferation coupled with epithelial polarity during development and human cancer.Support or Funding InformationNFR‐2017R1A2B3002241 funded by the Korean government (MSIP) andBK 21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

New insights into a decerebrate feline model of swallow‐breathing coordination

In the medulla, the swallow and respiratory central pattern generators (CPGs) interact to coordinate swallow initiation and permit swallow execution during the expiratory phase of breathing. Disruption of swallow‐breathing coordination can result in dysphagia, which is a major cause of morbidity and mortality in many neuro‐muscular diseases, especially stroke. Despite extensive study, the precise mechanisms of swallow‐breathing coordination are not known. We tested the hypothesis that both central inspiratory activity and vagal feedback from the lungs are key elements for effective swallow‐breathing coordination. Swallows were triggered by electrical stimulation of the superior laryngeal nerves (SLN) or by injection of water into the pharyngeal cavity in decerebrate, paralyzed and artificially ventilated cats while motor activities were recorded from phrenic, hypoglossal, lumbar and vagal nerves. Mechanical ventilation was either triggered by central inspiratory activity or set independently from the phrenic activity to alter the timing of bronchopulmonary vagal afferent input and allow analysis of its influence on swallow‐breathing coordination. We observed two types of swallows that produced opposite effects on central respiratory‐rhythm resetting across all conditions: post‐Inspiratory type swallows disrupted central I activity without affecting expiration, whereas expiratory type swallows prolonged expiration without affecting central inspiratory activity. Repetitive swallows observed during apnea reset the E2 phase of central respiration and produced facilitation of swallow motor output. Moreover, swallow initiation was negatively modulated by vagal feedback and was reset by lung inflation. Collectively, these findings support a reciprocal inhibition between central inspiration and the swallow CPG and they are consistent with a role for pulmonary stretch receptors in the coordination between brainstem CPGs for breathing and swallowing. They may also prove relevant for healthcare management of dysphagia.Support or Funding InformationOT2OD023854‐01, HL109025This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

An Interneuron Circuit Reproducing Essential Spectral Features of Field Potentials.

Recent advances in engineering and signal processing have renewed the interest in invasive and surface brain recordings, yet many features of cortical field potentials remain incompletely understood. In the computational study that follows, we show that a model circuit of interneurons, coupled via both GABAA receptor synapses and electrical synapses, reproduces many essential features of the power spectrum of local field potential (LFP) recordings, such as 1/ f power scaling at low frequency (below 10 Hz), power accumulation in the γ-frequency band (30-100 Hz), and a robust α rhythm in the absence of stimulation. The low-frequency 1/ f power scaling depends on strong reciprocal inhibition, whereas the α rhythm is generated by electrical coupling of intrinsically active neurons. As in previous studies, the γ power arises through the amplification of single-neuron spectral properties, owing to the refractory period, by parameters that favor neuronal synchrony, such as delayed inhibition. This study also confirms that both synaptic and voltage-gated membrane currents contribute substantially to the LFP and that high-frequency signals such as action potentials quickly taper off with distance. Given the ubiquity of electrically coupled interneuron circuits in the mammalian brain, they may be major determinants of the recorded potentials.

The Elicitation of Relaxation and Interoceptive Awareness Using Floatation Therapy in Individuals With High Anxiety Sensitivity

BackgroundFloatation-REST (Reduced Environmental Stimulation Therapy), an intervention that attenuates exteroceptive sensory input to the nervous system, has recently been found to reduce state anxiety across a diverse clinical sample with high levels of anxiety sensitivity (AS). To further examine this anxiolytic effect, the present study investigated the affective and physiological changes induced by Floatation-REST and assessed whether individuals with high AS experienced any alterations in their awareness for interoceptive sensation while immersed in an environment lacking exteroceptive sensation. MethodsUsing a within-subject crossover design, 31 participants with high AS were randomly assigned to undergo a 90-minute session of Floatation-REST or an exteroceptive comparison condition. Measures of self-reported affect and interoceptive awareness were collected before and after each session, and blood pressure was measured during each session. ResultsRelative to the comparison condition, Floatation-REST generated a significant anxiolytic effect characterized by reductions in state anxiety and muscle tension and increases in feelings of relaxation and serenity (p < .001 for all variables). Significant blood pressure reductions were evident throughout the float session and reached the lowest point during the diastole phase (average reduction >12 mm Hg). The float environment also significantly enhanced awareness and attention for cardiorespiratory sensations. ConclusionsFloatation-REST induced a state of relaxation and heightened interoceptive awareness in a clinical sample with high AS. The paradoxical nature of the anxiolytic effect in this sample is discussed in relation to Wolpe’s theory of reciprocal inhibition and the regulation of distress via sustained attention to present moment visceral sensations such as the breath.

Facilitation of antagonist motor output through short-latency sensory pathways during postnatal development in the mouse

Reciprocal inhibition of motor neurons via Ia inhibitory interneurons recruited by stimulation of proprioceptive afferents supplying antagonist muscles has been well described. Changes in the efficacy of inhibition, and sometimes even a switch from inhibition to facilitation, have been reported in the literature after disruption of descending pathways. We sought to test whether such facilitation could be expressed in normal animals by evaluating the presence of facilitation in acute preparations from uninjured animals. Using an isolated spinal cord preparation from neonatal mice, changes in the monosynaptic stretch reflex response in knee flexor motor neurons (posterior biceps semitendinosus; PBST) were monitored following conditioning stimulation of proprioceptive sensory afferents in other muscle nerves. As expected for reciprocal inhibition, conditioning by stimulation of quadriceps (knee extensors and PBST antagonists) sensory afferents resulted in inhibition of the stretch reflex response. Facilitation, however, of the stretch reflex response by quadriceps conditioning stimulation was observed when the glycinergic reciprocal inhibitory pathway was blocked by application of strychnine. Facilitation was elicited by low-threshold proprioceptive afferents and occurred at latencies consistent with a disynaptic circuit. The magnitude of facilitation was larger at birth than at one week postnatal. Our results also suggest reciprocal facilitation is restricted to antagonist muscle pairs, as facilitation of PBST responses was not observed when conditioned with the obturator nerve supplying the adductor muscles. Overall, these data suggest the efficacy of facilitation is modulated during the first postnatal week, while the specificity of facilitation is already established by birth.

Voluntary contraction enhances spinal reciprocal inhibition induced by patterned electrical stimulation in patients with stroke.

Reciprocal inhibition (RI) may be important for recovering locomotion after stroke. Patterned electrical stimulation (PES) can modulate RI in a manner that could be enhanced by voluntary muscle contraction (VC). To investigate whether VC enhances the PES-induced spinal RI in patients with stroke. Twelve patients with chronic stroke underwent three 20 min tasks, each on different days: (1) PES (10 pulses, 100 Hz every 2 s) applied to the common peroneal nerve; (2) VC consisting of isometric contraction of the affected-side tibialis anterior muscle; (3) PES combined with VC (PES + VC). RI from the tibialis anterior to the soleus muscle was assessed before, immediately after, and 10, 20, and 30 min after the task. Compared to the baseline, PES + VC significantly increased the changes in reciprocal inhibition at immediately after and 10 min after the task. PES alone significantly increased this change immediately after the task, while VC alone showed no significant increase. VC enhanced the PES-induced plastic changes in RI in patients with stroke. This effect can potentially increase the success rate of newer neurorehabilitative approaches in achieving functional recovery after stroke.

Comparison of a foam rolling session with active joint motion and without joint motion: A randomized controlled trial

BackgroundFoam rolling has become a popular form of self-myofascial release or roller massage among health and fitness professionals. Due to this popularity, foam roller devices can be found in many clinical and fitness settings. Despite the popularity, there are still several unknowns regarding foam rolling such the optimal technique. Specifically, there is a lack of research analyzing different foam roll techniques such as combining active joint motion with foam rolling. PurposeThe purpose of this study was to compare the effects of a foam rolling session to the left quadriceps with active joint motion and without joint motion on passive knee flexion range of motion (ROM) and pressure pain thresholds (PPT). MethodsThirty healthy adults were randomly allocated to one of two intervention groups: active joint motion and no joint motion. Each foam roll intervention to the left quadriceps lasted a total of 2 min. Dependent variables included passive knee flexion ROM and pressure pain threshold measures (PPT). Statistical analysis included subject demographic calculations and appropriate parametric and non-parametric tests to measure changes within and between intervention groups. ResultsFor left knee ROM, the active joint motion group demonstrated the greatest immediate increase in passive ROM (8°, p < .001) than the non-motion group (5°, p < .001). For PPT, the active joint motion group demonstrated the greatest immediate increase (180 kPa, p < .001) followed by the non-motion group (133 kPa, p < .001). Between group comparisons revealed a significance between groups for passive knee ROM (p < .001) and PPT (p < .001). ConclusionA short session of foam rolling with active joint motion appears to have a greater effect on passive joint ROM and PPT than rolling without motion. These observed changes may be influenced by the agonistic muscle activity during active motion. This activity may modulate activity of the antagonist muscle through reciprocal inhibition and other neural pathways. Future research is needed to confirm these findings.

Adenosine A1 Receptor-Mediated Attenuation of Reciprocal Dendro-Dendritic Inhibition in the Mouse Olfactory Bulb.

It is well described that A1 adenosine receptors inhibit synaptic transmission at excitatory synapses in the brain, but the effect of adenosine on reciprocal synapses has not been studied so far. In the olfactory bulb, the majority of synapses are reciprocal dendro-dendritic synapses mediating recurrent inhibition. We studied the effect of A1 receptor activation on recurrent dendro-dendritic inhibition in mitral cells using whole-cell patch-clamp recordings. Adenosine reduced dendro-dendritic inhibition in wild-type, but not in A1 receptor knock-out mice. Both NMDA receptor-mediated and AMPA receptor-mediated dendro-dendritic inhibition were attenuated by adenosine, indicating that reciprocal synapses between mitral cells and granule cells as well as parvalbumin interneurons were targeted by A1 receptors. Adenosine reduced glutamatergic self-excitation and inhibited N-type and P/Q-type calcium currents, but not L-type calcium currents in mitral cells. Attenuated glutamate release, due to A1 receptor-mediated calcium channel inhibition, resulted in impaired dendro-dendritic inhibition. In behavioral tests we tested the ability of wild-type and A1 receptor knock-out mice to find a hidden piece of food. Knock-out mice were significantly faster in locating the food. Our results indicate that A1 adenosine receptors attenuates dendro-dendritic reciprocal inhibition and suggest that they affect odor information processing.

Deterministic stability regimes and noise-induced quasistable behavior in a pair of reciprocally inhibitory neurons

Reciprocal inhibition is a common motif exploited by neuronal networks; an intuitive and tractable way to examine the behaviors produced by reciprocal inhibition is to consider a pair of neurons that synaptically inhibit each other and receive constant or noisy excitatory driving currents. In this work, we examine reciprocal inhibition using two models (a voltage-based and a current-based integrate-and-fire model with instantaneous or temporally structured input), and we use analytic and computational tools to examine the bifurcations that occur and study the various possible monostable, bistable, and tristable regimes that can exist; we find that, depending on system parameters (and on choice of neuron model), there can exist up to 3 distinct monostable regimes (denoted M0, M1, M2), 3 distinct bistable regimes (denoted B, B1, B2), and a single tristable regime (denoted T). We also find that synaptic inhibition exerts independent control over the two neurons – inhibition from neuron 1 to neuron 2 governs the spiking behavior of neuron 2 but has no impact on the spiking behavior of neuron 1 (and vice versa). The excitatory driving current, however, does not exhibit this property – the excitatory current to neuron 1 affects the spiking behavior of both neurons 1 and 2 (as does the excitatory current to neuron 2). Furthermore, we develop a methodology to examine the behavior of the system when the excitatory driving currents are allowed to be noisy, and we investigate the relationship between the behavior of the noisy system with the stability regime of the corresponding deterministic system.

Pharmacokinetic Interaction Study of Ketamine and Rhynchophylline in Rat Plasma by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry.

Eighteen Sprague-Dawley rats were randomly divided into three groups: ketamine group, rhynchophylline group, and ketamine combined with rhynchophylline group (n = 6). The rats of two groups received a single intraperitoneal administration of 30 mg/kg ketamine and 30 mg/kg rhynchophylline, respectively, and the third group received combined intraperitoneal administration of 30 mg/kg ketamine and 30 mg/kg rhynchophylline together. After blood sampling at different time points and processing, the concentrations of ketamine and rhynchophylline in rat plasma were determined by the established ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Chromatographic separation was achieved using a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with carbamazepine as an internal standard (IS). The initial mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with gradient elution. Multiple reaction monitoring (MRM) modes of m/z 238.1 → 179.1 for ketamine, m/z 385.3 → 159.8 for rhynchophylline, and m/z 237.3 → 194.3 for carbamazepine (IS) were utilized to conduct quantitative analysis. Calibration curve of ketamine and rhynchophylline in rat plasma demonstrated good linearity in the range of 1-1000 ng/mL (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Moreover, the intra- and interday precision relative standard deviation (RSD) of ketamine and rhynchophylline were less than 11% and 14%, respectively. This sensitive, rapid, and selective UPLC-MS/MS method was successfully applied to pharmacokinetic interaction study of ketamine and rhynchophylline after intraperitoneal administration. The results showed that there may be a reciprocal inhibition between ketamine and rhynchophylline.

Effect of the combination of motor imagery and electrical stimulation on upper extremity motor function in patients with chronic stroke: preliminary results.

Background:The combination of motor imagery (MI) and afferent input with electrical stimulation (ES) enhances the excitability of the corticospinal tract compared with motor imagery alone or electrical stimulation alone. However, its therapeutic effect is unknown in patients with hemiparetic stroke. We performed a preliminary examination of the therapeutic effects of MI + ES on upper extremity (UE) motor function in patients with chronic stroke.Methods:A total of 10 patients with chronic stroke demonstrating severe hemiparesis participated. The imagined task was extension of the affected finger. Peripheral nerve electrical stimulation was applied to the radial nerve at the spiral groove. MI + ES intervention was conducted for 10 days. UE motor function as assessed with the Fugl–Meyer assessment UE motor score (FMA-UE), the amount of the affected UE use in daily life as assessed with a Motor Activity Log (MAL-AOU), and the degree of hypertonia in flexor muscles as assessed with the Modified Ashworth Scale (MAS) were evaluated before and after intervention. To assess the change in spinal neural circuits, reciprocal inhibition between forearm extensor and flexor muscles with the H reflex conditioning-test paradigm at interstimulus intervals (ISIs) of 0, 20, and 100 ms were measured before and after intervention.Results:UE motor function, the amount of the affected UE use, and muscle hypertonia in flexor muscles were significantly improved after MI + ES intervention (FMA-UE: p < 0.01, MAL-AOU: p < 0.01, MAS: p = 0.02). Neurophysiologically, the intervention induced restoration of reciprocal inhibition from the forearm extensor to the flexor muscles (ISI at 0 ms: p = 0.03, ISI at 20 ms: p = 0.03, ISI at 100 ms: p = 0.01).Conclusion:MI + ES intervention was effective for improving UE motor function in patients with severe paralysis.

Effect of Reciprocal inhibition and Post Isometric relaxation; types of muscle energy technique in Piriformis syndrome ? A Comparative study

Effect of Reciprocal inhibition and Post Isometric relaxation; types of muscle energy technique in Piriformis syndrome ? A Comparative study

Autogenic inhibition versus reciprocal inhibition techniques on spastic children

Autogenic inhibition versus reciprocal inhibition techniques on spastic children