Journal of neurophysiology最新文献

Propriospinal interneurons in the spinal cord integrate multiple modalities of supraspinal and sensory inputs to modulate motor activity and facilitate complex motor behaviors, such as locomotion, skilled reaching, or grasping. The important ability of modulating motor activity in response to changes in the environment is partly mediated by a population of spinal interneurons marked by the expression Isl1, called dI3 neurons. These dI3 neurons are located throughout the cervical and lumbar spinal cord, receive cutaneous and proprioceptive feedback, and project to motoneurons. Previous work has demonstrated that dI3s are implicated in cutaneous-evoked reflexes and play a role in behaviors such as locomotion and grip strength, as well as motor recovery after spinal cord injury; however, it is unclear how different dI3 populations are connected to motor networks across the spinal cord to facilitate these diverse and complex functions. Through optogenetic activation of individual dI3 subpopulations located in different segments of the spinal cord, we mapped the functional connectivity of dI3 premotor circuits across the lumbar and cervical enlargements. We demonstrate that individual dI3 subpopulations have unique connectivity patterns and together form short and long propriospinal circuits that are either ipsilateral or commissural. Our findings suggest that dI3 subpopulations modulate the activity of distinct motor pools to differentially modulate complex motor functions such as grasping or locomotion.NEW & NOTEWORTHY We used an isolated mouse spinal cord preparation to optogenetically stimulate individual subpopulations of dI3 neurons. We investigated for the first time the specific connectivity patterns of dI3 neurons and demonstrated that they activate premotor circuits beyond their local segment, including short propriospinal, long propriospinal, and commissural circuits.

Adaptation to consistently occurring sensorimotor errors is considered obligatory in nature. We probed the robustness of this finding by asking if humans can selectively attenuate adaptation based on the task-relevance of error signals. Subjects made planar reaches to three different targets: an arc (experiment 1), a bar (experiment 2), and a point (experiment 3). During the reach, perturbations in extent (visuomotor gain), direction (visuomotor rotation), or both simultaneously were employed. In experiment 1, subjects showed robust adaptation to the rotation when reaching to the arc, even though the presence of this perturbation was irrelevant for the achievement of the task goal. Interestingly, however, rotation adaptation was strongly attenuated when it was presented simultaneously with a task-relevant gain perturbation. In experiment 2, which involved reaches to the bar, again, subjects successfully adapted to the task-irrelevant gain perturbation when it occurred in isolation. However, adaptation was attenuated when the gain co-occurred with a task-relevant rotation. Experiment 3 revealed that the attenuation observed in the first two experiments was not due to an inability to adapt to co-occurring rotation and gain perturbations. Collectively, our results suggest that the sensorimotor system selectively tunes learning in the presence of multiple error signals, a finding that can potentially be explained by a biased competition mechanism. That is, given limited processing capacity, a salient attribute-the relevance of the error to the task goal in this case-is prioritized for processing and drives subsequent adaptive changes in motor output.NEW & NOTEWORTHY The motor system continuously uses error feedback to recalibrate movements in response to changes in body and environmental conditions. Such error-based adaptation is thought to be obligatory, occurring whenever error signals are present, and even if the learning interferes with the achievement of the task goal. Contrary to this classical view, we demonstrate selective modulation of motor adaptation in the presence of multiple error signals based on their task-relevance.

Intracortical microstimulation (ICMS) is a technique to provide tactile sensations for a somatosensory brain-machine interface (BMI). A viable BMI must function within the rich, multisensory environment of the real world, but how ICMS is integrated with other sensory modalities is poorly understood. To investigate how ICMS percepts are integrated with visual information, ICMS and visual stimuli were delivered at varying times relative to one another. Both visual context and ICMS current amplitude were found to bias the qualitative experience of ICMS. In two tetraplegic participants, ICMS and visual stimuli were more likely to be experienced as occurring simultaneously in a realistic visual condition compared with an abstract one, demonstrating an effect of visual context on the temporal binding window. The peak of the temporal binding window varied but was consistently offset from zero, suggesting that multisensory integration with ICMS can suffer from temporal misalignment. Recordings from primary somatosensory cortex (S1) during catch trials where visual stimuli were delivered without ICMS demonstrated that S1 represents visual information related to ICMS across visual contexts. This study was a part of a clinical trial (NCT01964261).NEW & NOTEWORTHY Little is known about how the brain integrates tactile sensations elicited through intracortical microstimulation (ICMS) with visual information. This work investigates how visual cues affect the perception of tactile sensations from ICMS in two human participants. The results suggest that visual context can influence the perceived timing and the qualitative nature of artificial sensations, which is directly relevant to the implementation of a viable brain-machine interface (BMI) for individuals with tactile impairments.

Merkel cells are excitable cells in the skin and the whisker hair follicles that detect tactile stimuli, leading to the sense of touch. Previous studies have identified Piezo2 channels as mechanical transducers in Merkel cells, and their activation excites Merkel cells to fire Ca²⁺ action potentials (APs), which subsequently transmit the tactile signal to Aβ-afferent terminals. However, ion channels involving the electrophysiological properties of Merkel cells remain incompletely studied. Here, we performed patch-clamp recordings from Merkel cells in rat whisker hair follicles to investigate K⁺ channels and their roles in the electrophysiological properties of Merkel cells. Robust outward currents could be evoked by depolarizing Merkel cells, which could be markedly inhibited by the voltage-gated K⁺ channel blocker tetraethylammonium (TEA). The outward currents were also significantly blocked by iberiotoxin, a big-conductance voltage- and calcium-activated K⁺ (BK) channel blocker, suggesting that BK channels contribute to the outward K⁺ currents in Merkel cells. Furthermore, the outward currents also consist of a rapidly inactivating current (IA), which could be inhibited by stromatoxin-1 and phrixotoxin-2, the Kv4.2 channel blockers. This indicates that Kv4.2 channels mediate the IA currents in Merkel cells. TEA and iberiotoxin significantly prolonged AP duration, indicating that BK channels play a role in AP repolarization in Merkel cells. Stromatoxin-1 depolarized the resting membrane potentials, indicating a role of Kv4.2 in the resting membrane potentials in Merkel cells. Collectively, our findings reveal the essential roles of BK channels and Kv4.2 channels in the intrinsic electrophysiological properties of Merkel cells, which may be essential in tactile signaling by Merkel cells.NEW & NOTEWORTHY Patch-clamp recordings were made from Merkel cells in rat whisker hair follicles. Big-conductance voltage- and calcium-activated K⁺ (BK) channels and Kv4.2 voltage-gated K⁺ channels were identified in Merkel cells. BK and Kv4.2 channels were involved in Merkel cell action potential repolarization and resting membrane potentials, respectively. By controlling the intrinsic electrophysiological properties of Merkel cells, BK and Kv4.2 channels may play a significant role in tactile encoding.

The ventral lateral nucleus (VL) in the human ventral group exhibits activity associated with active and passive limb movements, and pathological movements found in patients with movement disorders. This group includes the anterior (VLa) and posterior (VLp) nuclei, which receive excitatory inputs from the deep cerebellar nuclei and inhibitory inputs from the internal segment of the globus pallidus (GPi). These nuclei primarily project to the primary and supplementary motor cortices. Despite differences in input sources, neurons in VLa and VLp often show similar activity patterns during active movements. In contrast, neurons in the cerebellar receiving nucleus respond more frequently during active movements, and microstimulation of these regions induces peripheral movements in monkeys, presumably due to their connections with the motor cortices. Neuronal activity in patients with movement disorders often mirrors the frequency of electromyographic (EMG) activity during disordered movements, with a cross-correlation observed between neuronal firing and EMG signals. A long history of research demonstrates that stereotactic ablation of the VL nucleus can lead to sustained improvements in some movement disorders, similar to the effects achieved through high-frequency stimulation of the VL nucleus through implanted deep brain stimulation (DBS) devices.NEW & NOTEWORTHY This review provides a comprehensive overview of the neurophysiology of the motor functions of the ventral lateral thalamus from recordings in patients and nonhuman primates. The results show that the diagnoses of movement disorders are associated with different, and discrete, anatomic and functional dimensions of movement.

Humans can acquire and maintain motor skills throughout their lives through motor learning. Motor learning and skill acquisition are essential for rehabilitation after neurological disease or injury. Adaptation, the initial stage of motor learning, involves short-term changes in motor performance in response to a new demand in the person's environment. Repeated adaptation can improve skill performance and result in long-term skill retention. Locomotor adaptation has been extensively studied with split-belt treadmill paradigms. In this study we explored whether bidirectional walking (BDW) on a split-belt treadmill can induce short-term gait adaptations. Twelve healthy volunteers participated in our single session, starting with 2 min of forward walking (FW), followed by four 5-min blocks of BDW with a 1-min passive rest in between blocks, and ending with another 2-min block of FW. We recorded body kinematics and ground reaction forces throughout the experiment. Participants modified both temporal (interlimb phasing, double stance duration) and spatial (step length) aspects of gait to meet the mechanical demands of backward dual walking (BDW). Adaptation occurred rapidly, with bilateral reductions in step length, adjustments in stance and swing phase timing, alterations in interlimb phasing, and decreased double stance duration in the limb walking backward. Notably, only the backward-walking limb (right) exhibited persistent aftereffects upon return to FW. These results demonstrate that BDW elicits adaptations in both spatial and temporal gait parameters, with transient aftereffects consistent with short-term motor learning. To our knowledge, this is the first report characterizing such spatiotemporal adaptations during BDW.NEW & NOTEWORTHY In this study, we demonstrate that bidirectional walking, i.e. walking with symmetrical limb speeds but in opposite directions, induces spatiotemporal adjustments and adaptations that persist for several minutes upon returning to forward walking. This study serves to validate bidirectional walking as a complementary paradigm to other split-belt training paradigms with unique biomechanical characteristics to investigate locomotor adaptation and learning.

Activation of airway sensory afferent nerves causes respiratory and autonomic reflexes. Most airway afferents are activated by noxious stimuli, such as inflammation, irritants, and pollutants. Activation evokes protective reflexes such as cough, bronchospasm, and changes in respiration and cardiovascular function. Airway nociceptors, projecting from the vagal ganglia (nodose and jugular ganglion), are heterogeneous with respect to gene expression and neuroanatomy. Here, we have characterized the cardiorespiratory reflexes in conscious mice evoked by activation of specific afferent subsets by inhaled stimuli. Capsaicin (TRPV1 agonist) and allyl isothiocyanate (AITC, TRPA1 agonist) evoked bradypnea associated with increased tidal volume and increased time of inspiration (T_I), expiration (T_E), and respiratory pause (T_P). AITC evoked greater bradycardia than capsaicin. AITC-evoked bradycardia was abolished by muscarinic inhibitor atropine, implicating a parasympathetic-mediated reflex. We expressed the chemogenetic hM3Dq DREADD receptor under the control of TRPV1^Cre (nociceptive), TRPV1^Flp (nociceptive), P2X2^Cre (nodose), or Tac1^cre (peptidergic) genes using various combinations of mouse models and intraganglionic injections of adeno-associated viral vectors. hM3Dq-expressing airway afferents were activated by inhalation of clozapine-N-oxide (CNO). CNO activation of TRPV1⁺ afferents evoked bradycardia and bradypnea, associated with increased T_I, T_E, and T_P. CNO activation of P2X2⁺ and vagal P2X2⁺TRPV1⁺ afferents evoked bradycardia and bradypnea, associated with increased T_P. CNO activation of Tac1⁺ afferents evoked bradycardia, whereas activation of vagal Tac1⁺TRPV1⁺ afferents evoked bradycardia and bradypnea, associated with increased T_E but not increased T_P. Our data suggest that multiple functionally distinct subsets of vagal nociceptors innervate the airways that can differentially regulate cardiorespiratory function.NEW & NOTEWORTHY This study uses intersectional chemogenetics, radiotelemetry, and whole body plethysmography to determine the effect of selective stimulation of distinct sensory nerve subsets on cardiorespiratory function in awake mice. We show that TRPA1⁺ afferents evoke greater reflex bradycardia than TRPV1⁺ afferents. We show that P2X2⁺ (nodose) afferents induce bradypnea through an increased time of pause, whereas Tac1⁺TRPV1⁺ (jugular nociceptive) afferents induce bradypnea through prolongation of expiration. Thus, distinct afferent subsets can differentially regulate cardiorespiratory function.

The size and material appearance of objects affect how much force we use to pick them up. We can also infer physical properties from how objects move when they collide, so it seems plausible that such cues might also affect our actions. To test this, we developed a hybrid virtual-reality/real-object paradigm in which seven participants viewed VR movies of collisions between visually identical spheres that varied only in apparent mass ratios and coefficients of restitution, while co-located real spheres mirrored the virtual objects' final positions. After watching each movie, participants were asked to pick each object up, while we measured the forces they used to do so. Our findings show that indeed lift forces depend on objects' motion after impact. Interestingly, this also caused an illusion of perceived weight, much like the classic size-weight and material-weight illusions. These results show that motion cues alone can shape both how we plan to lift and how heavy we feel an object is.NEW & NOTEWORTHY This study introduces a novel dynamic weight illusion, demonstrating that the sensorimotor system integrates conservation of momentum into both motor planning and perceptual weight judgments. By using a hybrid VR-real object paradigm with millimeter-level motion tracking, we show that dynamic relational cues-not just static object features-bias anticipatory force and explicit perception. These findings reveal a direct perceptual encoding of physical interactions, offering new insight into how intuitive physics is grounded in sensorimotor systems.

The purpose was to assess whether voluntary descending drive is obligatory to reduce maximal motor unit (MU) firing rates following high-intensity muscle fatiguing activation. Maximal MU firing rates were compared following a sustained 60-s maximal voluntary contraction (MVC) and separately following 60 s of maximal tetanic peripheral nerve stimulation (decaying rate 40 to 20 Hz) at high torque levels (initial torque ∼81% MVC). In ten participants, grouped firing rates of 2,290 MUs from the tibialis anterior were recorded with intramuscular tungsten microelectrodes. Baseline MU firing rates during dorsiflexion MVC were 40 ± 11.5 Hz. Immediately (∼2 s) after both tasks, MVC torque (P = 0.08) and maximal MU firing rates (P = 0.14) were depressed equally (all ∼30%, P < 0.001). After 10 min of rest, MVC torque recovered to baseline values following both tasks (P ≥ 0.17) and maximal firing rates recovered similarly (P = 0.12) in both tasks throughout recovery and returned to ∼95% of baseline values (P ≤ 0.02) by 10 min. Furthermore, there were negative correlations (all P ≤ 0.003) between MU firing rates with both electrically evoked doublet half-relaxation time (r = -0.48, r = -0.38) and contraction time (r = -0.39, r = -0.38) during recovery from both fatiguing tasks. These results indicate that factors related to voluntary activation of descending pathways are not directly responsible for the frequently observed reduction of maximal MU firing rates after sustained high-intensity activation. On the contrary, with nonvolitional induced contractile failure, firing rates declined similarly to the voluntary task, providing novel support for peripheral feedback mechanisms as the primary regulator of firing rate during this fatiguing task.NEW & NOTEWORTHY Maximal motor unit firing rates similarly decline and recover following 60 s of sustained maximal voluntary contraction or tetanic peripheral nerve stimulation at high torque levels. Therefore, voluntary activation of descending tracts is not an obligatory contributor to reduction of maximal firing rates after sustained high-intensity activation. On the contrary, with nonvolitional induced contractile failure (i.e., electrical stimulation), firing rates declined similarly to voluntary fatigue, providing novel support for peripheral feedback mechanisms that inhibit MU firing rate.

Spinally projecting serotonergic (5-HTsp) neurons represent a heterogeneous population of brainstem neurons whose relevance to the control of movement has largely been inferred. Numerous studies across multiple species have suggested that 5-HTsp neurons exert a widespread influence on spinal sensorimotor networks, operating at multiple levels (primary afferents, interneurons, and motoneurons) through various serotonin receptor subtypes. However, despite the anatomical and neurochemical complexity of the 5-HTsp system, supporting evidence has been mostly derived from indirect approaches [e.g., exogenous application of serotonin (5-HT) and agonists/antagonists of 5-HT receptors]. Direct demonstrations of specific anatomical and functional connectivity have been limited, occasionally yielding discrepant results. Consequently, as the primary provider of serotonin to the spinal cord, the exact contributions of 5-HTsp neurons remain to be fully elucidated. For this mini-review, we sifted through the literature of the last six decades, starting after the characterization of brainstem raphe nuclei and monoaminergic systems, to provide a clearer picture of the anatomy and influences of different 5-HTsp neuron populations on sensorimotor circuits and motor behaviors. We focused on studies reporting direct manipulation of brainstem 5-HTsp neurons, excluding those targeting 5-HT neurotransmission by exogenous application of 5-HT. This emphasis aims to highlight the urgency of resolving how 5-HTsp neuron subpopulations differentiate anatomically and functionally so they can be integrated as dedicated components in current models of supraspinal control of movement and motor diseases such as Parkinson's and amyotrophic lateral sclerosis. Along the way, we point out gaps in knowledge that may be filled using newly available research tools.