Journal of neurophysiology最新文献

Acoustic stimuli where the spectrum is time-varying are ubiquitous in natural sounds, including animal vocalizations, human speech, and music. Early studies of such stimuli involving frequency-modulated sweeps reveal that neurons in the primary auditory cortex of a variety of mammals show differences in firing rates depending on either the direction of the sweep and/or the sweep velocity. Psychophysical studies have also shown that the perception of such time-varying stimulus parameters is quite acute, underscoring the importance of such signals in normal acoustic perception. The responses of auditory neurons in alert primates have been little studied, and there is limited information relating neural activity to the perception of these signals. In this study, we investigated the neural discriminability of sweep direction and velocity for frequency-modulated sweeps presented to alert rhesus macaque monkeys in both core and belt auditory cortical areas. We quantified how well these information-bearing parameters were encoded using spike train pattern discriminators, and compared decoder performance when neural responses were restricted to temporal patterns or firing rates. Decoding accuracy for firing rate alone exceeded chance, and rate-normalized, spike-timing information was essentially equivalent to the complete firing pattern. Although most belt areas showed small decreases in decoding accuracy relative to the primary field, all fields encoded and represented sweeps similarly. Thus, there was little evidence of hierarchical processing between core and belt fields for these stimuli, indicating that frequency modulation sweep direction and velocity are not specifically extracted in the early auditory cortical hierarchy.NEW & NOTEWORTHY We recorded responses of single neurons in core and belt auditory cortical fields in alert macaque monkeys to frequency-modulated sounds, key feature of many natural sounds, including speech and vocalizations. We found that the timing of neural activity, rather than its magnitude, explained decoding accuracy in all cortical areas, and we did not observe compelling evidence of improved discriminability in core or belt fields beyond that seen in the primary auditory cortex.

Motor adaptation is a learning process that enables humans to regain proficiency when sensorimotor conditions are sustainably altered. Many studies have documented the properties of motor adaptation, yet the underlying mechanisms of motor adaptation remain imperfectly understood. In this study, we propose a computational analysis of adaptation to a visuomotor rotation task and examine it through an experiment. Our analysis suggests that two distinct processes contribute to produce adaptation: one which straightens trajectories, and another which redirects trajectories. We designed a visuomotor rotation task in a three-dimensional (3-D) virtual environment where human participants performed a pointing task using a head-mounted display controller represented by a cursor that was visually rotated by an angular deviation relative to its actual position. We observed that: 1) the trajectories were initially curved and misdirected, and became straighter and better directed with learning; 2) the straightening process occurred faster than the redirection process. These findings are consistent with our computational analysis and disclose a new and different perspective on motor adaptation.NEW & NOTEWORTHY This study investigates the visuomotor rotation protocol using a pointing task to compare the adaptation of 1) the movement initial angle, 2) the trajectory length. The experiment shows that these two outcomes adapt on different time scales. To account for this observation, we propose a computational analysis based on the control-estimation framework.

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.