Journal of neurophysiology最新文献

Growing evidence indicates that activation of cannabinoid type 2 (CB2) receptors protects dopamine neurons in the pathogenesis of Parkinson's disease (PD). However, the mechanisms underlying neuroprotection mediated by CB2 receptors are still elusive. In this study, we investigated the effects of CB2 receptor activation on 6-hydroxydopamine (6-OHDA)-induced dopamine neuron degeneration and iron accumulation in the substantia nigra (SN) of rats. We found that treatment with JWH133, a selective CB2 receptor agonist, significantly improved the apomorphine (APO)-induced rotational behavior in 6-OHDA-treated rats. The decreased numbers of tyrosine hydroxylase (TH)-positive neurons and reduced TH protein expression in the lesioned SN of rats were effectively restored by JWH133. Moreover, we found that JWH133 inhibited the increase of iron-staining cells in the lesioned SN of rats. To explore the protective mechanisms of activation of CB2 receptors on dopamine neurons, we further observed the effect of JWH133 on 1-methyl-4-phenylpyridinium (MPP⁺)-treated primary cultured ventral mesencephalon (VM) neurons from rats. We found that JWH133 significantly inhibited the increase of intracellular reactive oxygen species (ROS), the activation of Caspase-3, the decrease of mitochondrial transmembrane potential (ΔΨm), and the decrease of Bcl-2/Bax protein expression caused by MPP⁺ treatment. JWH133 also inhibited the MPP⁺-induced upregulation of divalent metal transporter-1 (DMT1) and downregulation of ferroportin 1 (FPN1). Furthermore, JWH133 also suppressed the MPP⁺-accelerated iron influx in the VM neurons. These results suggest that activation of CB2 receptor suppresses MPP⁺-induced cellular iron accumulation and prevents neurodegeneration.NEW & NOTEWORTHY Expression of cannabinoid type 2 receptors (CB2Rs) was discovered on dopamine neurons in recent years. The role of CB2R expressed on dopamine neurons in the pathogenesis of Parkinson's disease (PD) has not been fully elucidated. The content of iron accumulation in the brain is closely related to the progress of PD. We verified the inhibitory effect of CB2R on iron deposition in dopamine neurons through experiments, which provided a new idea for the treatment of PD.

Motor adaptation is attenuated when sensory feedback about the movement is uncertain. Although this was initially shown for small visual errors, attenuation seems not to hold when visual errors are larger and the contributions of implicit adaptation are isolated with the error-clamp method, which makes visual feedback task-irrelevant. Here we ask whether adaptation to a similarly large perturbation is attenuated when task-relevant visual feedback is uncertain. In a first experiment, we tested participants on a 30° movement-contingent visuomotor rotation under both low (cursor) and high (cloud of moving dots) visual feedback uncertainty. In line with optimal integration, we found that the early increase in adaptation and final extent of adaptation were reduced with high feedback uncertainty. In a second experiment, we included several blocks of no-feedback trials during the perturbation block to quantify the contribution of implicit adaptation. Results showed that implicit adaptation was smaller with high compared to low feedback uncertainty throughout the perturbation block. The estimated contribution of explicit adaptation was overall small, particularly for high feedback uncertainty. Our results demonstrate an influence of task-relevant visual feedback, and the resulting target errors, on implicit adaptation. We show that our motor system is sensitive to the feedback it receives even for larger error sizes and accordingly adjusts its learning properties when our ability to achieve the task goal is affected.NEW & NOTEWORTHY Motor adaptation is linked to the estimation of our actions. Whereas uncertainty of task-irrelevant visual feedback appears not to influence implicit adaptation for errors beyond a certain size, here we tested whether this is still the case for task-relevant feedback. We show that implicit adaptation is attenuated when task-relevant visual feedback is uncertain, suggesting a dependency on the assessment of not just sensory prediction errors but also target errors.

Alzheimer's disease (AD) was described more than a century ago. However, there are still no effective approaches to its treatment, which may suggest that the search for the cure is not being conducted in the most productive direction. AD begins as selective impairments of declarative memory with no deficits in other cognitive functions. Therefore, understanding of the AD pathogenesis has to include the understanding of this selectivity. Currently, the main efforts aimed at prevention and treatment of AD are based on the dominating hypothesis for the AD pathogenesis: the amyloid hypothesis. But this hypothesis does not explain selective memory impairments since β-amyloid accumulates extracellularly and should be toxic to all types of cerebral neurons, not only to "memory engram neurons." To explain selective memory impairment, I propose the autoimmune hypothesis of AD, based on the analysis of risk factors for AD and molecular mechanisms of memory formation. Memory formation is associated with epigenetic modifications of chromatin in memory engram neurons and, therefore, might be accompanied by the expression of memory-specific proteins recognized by the adaptive immune system as "non-self" antigens. Normally, the brain is protected by the blood-brain barrier (BBB). All risk factors for AD provoke BBB disruptions, possibly leading to an autoimmune reaction against memory engram neurons. This reaction would make them selectively sensitive to tauopathy. If this hypothesis is confirmed, the strategies for AD prevention and treatment would be radically changed.

Neurostimulation/neurorecording are tools to study, diagnose, and treat neurological/psychiatric conditions. Both techniques depend on volume conduction between scalp and excitable brain tissue. Here, we examine how neurostimulation with transcranial magnetic stimulation (TMS) is affected by hydration status, a physiological variable that can influence the volume of fluid spaces/cells, excitability, and cellular/global brain functioning. Normal healthy adult participants (32, 9 males) had common motor TMS measures taken in a repeated-measures design from dehydrated (12-h overnight fast/thirst) and rehydrated (identical dehydration protocol followed by rehydration with 1 L water in 1 h) testing days. The target region was left primary motor cortex hand area. Response at the target muscle was recorded with electromyography. Urinalysis confirmed hydration status. Motor hotspot shifted in half of participants. Motor threshold decreased in rehydration, indicating increased excitability. Even after redosing/relocalizing TMS to the new threshold/hotspot, rehydration still showed evidence of increased excitability: recruitment curve measures generally shifted upward and the glutamate-dependent paired-pulse protocol, short intracortical facilitation (SICF), was increased. Short intracortical inhibition (SICI), long intracortical inhibition (LICI), long intracortical facilitation (LICF), and cortical silent period (CSP) were relatively unaffected. The hydration perturbations were mild/subclinical based on the magnitude/speed and urinalysis. Motor TMS measures showed evidence of expected physiological changes of osmotic challenges. Rehydration showed signs of macroscopic and microscopic volume changes including decreased scalp-cortex distance (brain closer to stimulator) and astrocyte swelling-induced glutamate release. Hydration may be a source of variability affecting any techniques dependent on brain volumes/volume conduction. These concepts are important for researchers/clinicians using such techniques or dealing with the wide variety of disease processes involving water balance.NEW & NOTEWORTHY Hydration status can affect brain volumes and excitability, which should affect techniques dependent on electrical volume conduction, including neurostimulation/recording. We test the previously unknown effects of hydration on neurostimulation with TMS and briefly review relevant physiology of hydration. Rehydration showed lower motor threshold, shifted motor hotspot, and generally larger responses even after compensating for threshold/hotspot changes. This is important for clinical and research applications of neurostimulation/neurorecording and the many clinical disorders related to water balance.

Postural stabilization is essential to effectively interact with our environment. Humans preemptively adjust their posture to counteract impending disturbances, such as those encountered during interactions with moving objects, a phenomenon known as anticipatory postural adjustments (APAs). APAs are thought to be influenced by predictive models that incorporate object motion via retinal motion and extraretinal signals. Building on our previous work that examined APAs in relation to the perceived momentum of moving objects, here we explored the impact of object motion within different visual field sectors on the human capacity to anticipate motion and prepare APAs for contact between virtual moving objects and the limb. Participants interacted with objects moving toward them under different gaze conditions. In one condition, participants fixated on either a central point (central fixation) or left-right of the moving object (peripheral fixation), whereas in another, they followed the moving object with smooth pursuit eye movements (SPEMs). We found that APAs had the smallest magnitude in the central fixation condition and that no notable differences in APAs were apparent between the SPEM and peripheral fixation conditions. This suggests that the visual system can accurately perceive motion of objects in peripheral vision for posture stabilization. Using Bayesian model averaging, we also evaluated the contribution of different gaze variables, such as eye velocity and gain (ratio of eye and object velocity) and showed that both eye velocity and gain signals were significant predictors of APAs. Taken together, our study underscores the roles of oculomotor signals in the modulation of APAs.NEW & NOTEWORTHY We show that the human visuomotor system can detect motion in peripheral vision and make anticipatory adjustments to posture before contact with moving objects, just as effectively as when the eye movement system tracks those objects with smooth pursuit eye movements. These findings pave the way for research into how age-induced changes in spatial vision, eye movements, and motion perception could affect the control of limb movements and postural stability during motion-mediated interactions with objects.

Reaching movements can be redirected during their progress to handle unexpected visual changes, such as a change in target location. It is important to know when these redirections start, i.e., the online reaction time (oRT), but this information is not readily evident since redirections are embedded within a time-varying baseline movement that differs from trial to trial. The one previous study that evaluated the performance of different oRT identification methods utilized simulated redirections with the exact same onset, rather than a range of onsets as would be typically encountered. We addressed this gap by utilizing batches of "hybrid" trials with temporal spread in their oRTs. Each hybrid trial combined a sampled baseline movement with an idealized corrective response. Two new methods had the most accurate identification of online reaction times: 1) a threshold-aligned grand mean regression, and 2) a template-based approach we term the canonical correction search. The threshold-aligned grand mean regression is simple to implement and effective. The canonical correction search is a more complex procedure but arguably better linked to the underlying response. Applying the two methods to a published dataset revealed more delayed oRTs than was previously reported along with new information such as the width of oRT distributions. Taken together, our results demonstrate the utility of two new methods for dissecting corrective action from ongoing movement.NEW & NOTEWORTHY Advancing our understanding of visual feedback control requires methods that accurately identify the onset of corrective action. We developed a modified regression approach and a template-based approach to identify the online reaction time of single-reaching movements. Both outperform previous methods when challenged by temporal jitter in the response onset and increased background noise.

The effectiveness of activated Ia afferents to discharge α-motoneurons is decreased during passive muscle lengthening compared with static and shortening muscle conditions. Evidence suggests that these regulations are explained by 1) greater postactivation depression induced by homosynaptic postactivation depression (HPAD) and 2) primary afferent depolarization (PAD). It remains uncertain whether muscle length impacts the muscle lengthening-related aspect of regulation of the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and heteronymous Ia facilitation (HF). We conducted a study involving 15 healthy young individuals. We recorded conditioned or nonconditioned soleus Hoffmann (H) reflex with electromyography (EMG) to estimate the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and HF during passive shortening, static, and lengthening muscle conditions at short, intermediate, and long lengths. Our results show that the decrease of effectiveness of activated Ia afferents to discharge α-motoneurons and increase of postactivation depression during passive muscle lengthening occur at all muscle lengths. For PAD and HF, we found that longer muscle length increases the magnitude of regulation related to muscle lengthening. To conclude, our findings support an inhibitory effect (resulting from increased postactivation depression) of muscle lengthening and longer muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons. The increase in postactivation depression associated with muscle lengthening can be attributed to the amplification of Ia afferents discharge.NEW & NOTEWORTHY Original results are that in response to passive muscle lengthening and increased muscle length, inhibition of the effectiveness of activated Ia afferents to discharge α-motoneurons increases, with primary afferent depolarization and homosynaptic postactivation depression mechanisms playing central roles in this regulatory process. Our findings highlight for the first time a cumulative inhibitory effect of muscle lengthening and increased muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons.

We frequently interact with textured surfaces with both our feet and hands. Like texture's importance for grasping, texture perception via the foot sole might provide important signals about the stability of a surface, aiding in maintaining balance. However, how textures are perceived by the foot, and especially under the high forces experienced during walking, is unknown. The current study builds on extensive research investigating texture perception at the hand by presenting everyday textures to the foot while stepping onto them, exploring them with the foot while sitting, and exploring them with the hand. Participants rated each texture along three perceptual dimensions: roughness, hardness, and stickiness. Participants also rated how stable their posture felt when standing upon each texture. Results show that perceptual ratings of each textural dimension were highly correlated across conditions. Hardness exhibited the greatest consistency and stickiness the weakest. Moreover, correlations between stepping and exploration with the foot were lower than those between exploration with the foot and exploration with the hand, suggesting that mode of interaction (high vs. low force) impacts perception more than body region used (foot vs. hand). On an individual level, correlations between conditions were higher than those between participants, suggesting that differences are greater between individuals than between mode of interaction or body region. When investigating the relationship to perceived stability, only hardness contributed significantly, with harder surfaces rated as more stable. Overall, tactile perception appears consistent across body regions and interaction modes, although differences in perception are greater during walking.NEW & NOTEWORTHY We frequently interact with textured surfaces using our feet, but little is known about how textures on the foot sole are perceived as compared with the hand. Here, we show that roughness, hardness, and stickiness ratings are broadly consistent when stepping on textures, exploring them with the foot sole, or with the hand. Hardness also contributes to perceived stability.

We studied simultaneous EMG and midline EEG responses, including over the cerebellum, in 10 standing subjects (35 ± 15 yr; 5 females, 5 males). Recordings were made following repeated taps to the sternum, stimuli known to evoke short-latency EMG responses in leg muscles, consistent with postural reflexes. EEG power had relatively more high-frequency components (>30 Hz) when recorded from electrodes over the cerebellum (Iz and SIz) compared with other midline electrodes. We confirmed a previous report using a similar stimulus that evoked short-latency potentials over the cerebellum. We showed clear midline-evoked EEG potentials occurring at short latency over the cerebellum (P23, N31, N42, and P54) and frontally (N28 and N57) before the previously described perturbation-evoked potential (P1/N1/P2). The P23 response correlated with the subsequent EMG response in the tibialis anterior muscles (r = 0.72, P = 0.018), confirming and extending previous observations. We did not find a correlation with the N1 amplitude. We conclude that early activity occurs from electrodes over the inion in response to a brief tap to the sternum. This is likely to represent cerebellar activity and it appears to modulate short-latency postural EMG responses.NEW & NOTEWORTHY We studied the effects of a brief tap to the sternum in human subjects, known to evoke short-latency postural responses. Using an extended EEG recording system, we showed early evoked responses over the midline cerebellum, including the P23 potential, which correlated with the EMG responses in tibialis anterior, consistent with a cerebellar role in postural reflexes. The stimulus also evoked later EEG responses, including the perturbation potential.