Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice.

Information transfer within neuronal circuits depends on the balance and recurrent activity of excitatory and inhibitory neurotransmission. Chloride (Cl-) is the major central nervous system (CNS) anion mediating inhibitory neurotransmission. Astrocytes are key homoeostatic glial cells populating the CNS, although the role of these cells in regulating excitatory-inhibitory balance remains unexplored. Here we show that astrocytes act as a dynamic Cl- reservoir regulating Cl- homoeostasis in the CNS. We found that intracellular chloride concentration ([Cl-]i) in astrocytes is high and stable during sleep. In awake mice astrocytic [Cl-]i is lower and exhibits large fluctuation in response to both sensory input and motor activity. Optogenetic manipulation of astrocytic [Cl-]i directly modulates neuronal activity during locomotion or whisker stimulation. Astrocytes thus serve as a dynamic source of extracellular Cl- available for GABAergic transmission in awake mice, which represents a mechanism for modulation of the inhibitory tone during sustained neuronal activity.

The Effect of Hyperoxia on Central and Peripheral Factors of Arm Flexor Muscles Fatigue Following Maximal Ergometer Rowing in Men.

PURPOSE: This study evaluates the effect of hyperoxia on cerebral oxygenation and neuromuscular fatigue mechanisms of the elbow flexor muscles following ergometer rowing. METHODS: In 11 competitive male rowers (age, 30 ± 4 years), we measured near-infrared spectroscopy determined frontal lobe oxygenation (ScO2) and transcranial Doppler ultrasound determined middle cerebral artery mean flow velocity (MCA V mean) combined with maximal voluntary force (MVC), peak resting twitch force (P tw) and cortical voluntary activation (VATMS) of the elbow flexor muscles using electrical motor point and magnetic motor cortex stimulation, respectively, before, during, and immediately after 2,000 m all-out effort on rowing ergometer with normoxia and hyperoxia (30% O2). RESULTS: Arterial hemoglobin O2 saturation was reduced to 92.5 ± 0.2% during exercise with normoxia but maintained at 98.9 ± 0.2% with hyperoxia. The MCA V mean increased by 38% (p < 0.05) with hyperoxia, while only marginally increased with normoxia. Similarly, ScO2 was not affected with hyperoxia but decreased by 7.0 ± 4.8% from rest (p = 0.04) with normoxia. The MVC and P tw were reduced (7 ± 3% and 31 ± 9%, respectively, p = 0.014), while VATMS was not affected by the rowing effort in normoxia. With hyperoxia, the deficit in MVC and P tw was attenuated, while VATMS was unchanged. CONCLUSION: These data indicate that even though hyperoxia restores frontal lobe oxygenation the resultant attenuation of arm muscle fatigue following maximal rowing is peripherally rather than centrally mediated.

Grid-climbing Behaviour as a Pain Measure for Cancer-induced Bone Pain and Neuropathic Pain.

Despite affecting millions of people, chronic pain is generally treated insufficiently. A major point of focus has been the lack of translation from preclinical data to clinical results, with the predictive value of chronic pain models being a major concern. In contrast to current focus on stimulus-based nociceptive responses in preclinical research, development of behavioural tests designed to quantify suspension of normal behaviour is likely a more equivalent readout for human pain-assessment tests. In this study, we quantified grid-climbing behaviour as a non-stimulus-evoked behavioural test for potential use as a measure of neuropathic and cancer-induced bone pain in mice. In both models, the grid-climbing test demonstrated pain-related sparing of the affected leg during climbing. In both models, the behaviour was reversed by administration of morphine, suggesting that the observed behaviour was pain-specific.

Gait variability and motor control in people with knee osteoarthritis.

Knee osteoarthritis (OA) is a common disease that impairs walking ability and function. We compared the temporal gait variability and motor control in people with knee OA with healthy controls. The purpose was to test the hypothesis that the temporal gait variability would reflect a more stereotypic pattern in people with knee OA compared with healthy age-matched subjects. To assess the gait variability the temporal structure of the ankle and knee joint kinematics was quantified by the largest Lyapunov exponent and the stride time fluctuations were quantified by sample entropy and detrended fluctuation analysis. The motor control was assessed by the soleus (SO) Hoffmann (H)-reflex modulation and muscle co-activation during walking. The results showed no statistically significant mean group differences in any of the gait variability measures or muscle co-activation levels. The SO H-reflex amplitude was significantly higher in the knee OA group around heel strike when compared with the controls. The mean group difference in the H-reflex in the initial part of the stance phase (control-knee OA) was -6.6% Mmax (95% CI: -10.4 to -2.7, p=0.041). The present OA group reported relatively small impact of their disease. These results suggest that the OA group in general sustained a normal gait pattern with natural variability but with suggestions of facilitated SO H-reflex in the swing to stance phase transition. We speculate that the difference in SO H-reflex modulation reflects that the OA group increased the excitability of the soleus stretch reflex as a preparatory mechanism to avoid sudden collapse of the knee joint which is not uncommon in knee OA.

Movement behavior of high-heeled walking: how does the nervous system control the ankle joint during an unstable walking condition?

The human locomotor system is flexible and enables humans to move without falling even under less than optimal conditions. Walking with high-heeled shoes constitutes an unstable condition and here we ask how the nervous system controls the ankle joint in this situation? We investigated the movement behavior of high-heeled and barefooted walking in eleven female subjects. The movement variability was quantified by calculation of approximate entropy (ApEn) in the ankle joint angle and the standard deviation (SD) of the stride time intervals. Electromyography (EMG) of the soleus (SO) and tibialis anterior (TA) muscles and the soleus Hoffmann (H-) reflex were measured at 4.0 km/h on a motor driven treadmill to reveal the underlying motor strategies in each walking condition. The ApEn of the ankle joint angle was significantly higher (p<0.01) during high-heeled (0.38±0.08) than during barefooted walking (0.28±0.07). During high-heeled walking, coactivation between the SO and TA muscles increased towards heel strike and the H-reflex was significantly increased in terminal swing by 40% (p<0.01). These observations show that high-heeled walking is characterized by a more complex and less predictable pattern than barefooted walking. Increased coactivation about the ankle joint together with increased excitability of the SO H-reflex in terminal swing phase indicates that the motor strategy was changed during high-heeled walking. Although, the participants were young, healthy and accustomed to high-heeled walking the results demonstrate that that walking on high-heels needs to be controlled differently from barefooted walking. We suggest that the higher variability reflects an adjusted neural strategy of the nervous system to control the ankle joint during high-heeled walking.

Origin of the low-level EMG during the silent period following transcranial magnetic stimulation.

OBJECTIVE: The cortical silent period refers to a period of near silence in the electromyogram (EMG) after transcranial magnetic stimulation (TMS) of the motor cortex during contraction. However, low-level EMG of unknown origin is often present. We hypothesised that it arises through spinal reflexes. Sudden lengthening of the muscle as force drops during the silent period could excite muscle spindles and facilitate motoneurones. METHODS: Subjects (n = 8) performed maximal isometric, shortening and lengthening contractions of the elbow flexors during which TMS (90-100% output) was delivered over the motor cortex. The rate of flexion during shortening contractions reduced muscle lengthening caused by muscle relaxation. Surface EMG was recorded from biceps brachii and brachioradialis, and the low-level EMG during silent periods produced by TMS was measured. RESULTS: Low-level EMG activity was reduced on average by 68% in biceps and 63% in brachioradialis in the shortening contraction compared to all other contraction conditions (p < 0.001). Levels of pre-stimulus EMG were similar between conditions. CONCLUSIONS: Muscle lengthening contributes to low-level EMG activity in the silent period, through spinal reflex facilitation by muscle spindle afferents. SIGNIFICANCE: The silent period depth is not only dependent on cortical output but also reflex effects evoked by muscle lengthening.

Neck pain and postural balance among workers with high postural demands - a cross-sectional study.

BACKGROUND: Neck pain is related to impaired postural balance among patients and is highly prevalent among workers with high postural demands, for example, cleaners. We therefore hypothesised, that cleaners with neck pain suffer from postural dysfunction. This cross-sectional study tested if cleaners with neck pain have an impaired postural balance compared with cleaners without neck pain. METHODS: Postural balance of 194 cleaners with (n = 85) and without (N = 109) neck pain was studied using three different tests. Success or failure to maintain the standing position for 30 s in unilateral stance was recorded. Participants were asked to stand on a force platform for 30 s in the Romberg position with eyes open and closed. The centre of pressure of the sway was calculated, and separated into a slow (rambling) and fast (trembling) component. Subsequently, the 95% confidence ellipse area (CEA) was calculated. Furthermore a perturbation test was performed. RESULTS: More cleaners with neck pain (81%) failed the unilateral stance compared with cleaners without neck pain (61%) (p < 0.01). However, the risk of failure in unilateral stance was statistically elevated in cleaners with concurrent neck/low back pain compared to cleaners without neck/low back pain (p < 0.01), whereas pain at only neck or only low back did not increase the risk. Impaired postural balance, measured as CEA (p < 0.01), rambling (p < 0.05) and trembling (p < 0.05) was observed among cleaners with neck pain in comparison with cleaners without neck pain in the Romberg position with eyes closed, but not with eyes open. CONCLUSIONS: Postural balance is impaired among cleaners with neck pain and the current study suggests a particular role of the slow component of postural sway. Furthermore, the unilateral stance test is a simple test to illustrate functional impairment among cleaners with concurrent neck and low back pain. TRIAL REGISTRATION: ISRCTN96241850.

Differential effects of low-intensity motor cortical stimulation on the inspiratory activity in scalene muscles during voluntary and involuntary breathing.

To assess the cortical contribution to breathing, low-intensity transcranial magnetic stimulation (TMS) was delivered over the motor cortex in 10 subjects during: (i) voluntary static inspiratory efforts, (ii) hypocapnic voluntary ventilation (end-tidal CO(2), 2.7±0.4% mean±SD), and (iii) hypercapnic involuntary ventilation (end-tidal CO(2), 6.0±0.7%). Electromyographic activity (EMG) was recorded from the scalene muscles (obligatory inspiratory muscles) and was significantly suppressed by TMS at short latency (17.2±1.7ms). The scalene EMG was reduced to 76±8% and 76±7% in voluntary breathing and the static inspiratory effort, respectively, but only to 91±10% during the involuntary ventilation, significantly less than during the two voluntary tasks (p<0.005). Thus, with differences in chemical drive to breathe, TMS shows differences in the cortical contribution to inspiratory activity in scalene muscles. Voluntary breathing showed larger suppression than involuntary breathing, when the suppression was marginal. The results strongly suggest that drive from fast-conducting corticospinal neurones contributes to inspiratory activity in scalenes during voluntary breathing but is not required during involuntary breathing.