Induction and Cancellation of Self-Motion Misperception by Asymmetric Rotation in the Light.

Asymmetrical sinusoidal whole-body rotation sequences with half-cycles at different velocities induce self-motion misperception. This is due to an adaptive process of the vestibular system that progressively reduces the perception of slow motion and increases that of fast motion. It was found that perceptual responses were conditioned by four previous cycles of asymmetric rotation in the dark, as the perception of self-motion during slow and fast rotations remained altered for several minutes. Surprisingly, this conditioned misperception remained even when asymmetric stimulation was performed in the light, a state in which vision completely cancels out the perceptual error. This suggests that vision is unable to cancel the misadaptation in the vestibular system but corrects it downstream in the central perceptual processing. Interestingly, the internal vestibular perceptual misperception can be cancelled by a sequence of asymmetric rotations with fast/slow half-cycles in a direction opposite to that of the conditioning asymmetric rotations.

Electromechanical coupling of the Kv1.1 voltage-gated K+ channel is fine-tuned by the simplest amino acid residue in the S4-S5 linker.

Investigating the Shaker-related K+ channel Kv1.1, the dysfunction of which is responsible for episodic ataxia 1 (EA1), at the functional and molecular level provides valuable understandings on normal channel dynamics, structural correlates underlying voltage-gating, and disease-causing mechanisms. Most studies focused on apparently functional amino acid residues composing voltage-gated K+ channels, neglecting the simplest ones. Glycine at position 311 of Kv1.1 is highly conserved both evolutionarily and within the Kv channel superfamily, is located in a region functionally relevant (the S4-S5 linker), and results in overt disease when mutated (p.G311D). By mutating the G311 residue to aspartate, we show here that the channel voltage-gating, activation, deactivation, inactivation, and window currents are markedly affected. In silico, modeling shows this glycine residue is strategically placed at one end of the linker helix which must be free to both bend and move past other portions of the protein during the channel's opening and closing. This is befitting of a glycine residue as its small neutral side chain allows for movement unhindered by interaction with any other amino acid. Results presented reveal the crucial importance of a distinct glycine residue, within the S4-S5 linker, in the voltage-dependent electromechanical coupling that control channel gating.

Long-lasting effects of neck muscle vibration and contraction on self-motion perception of vestibular origin.

OBJECTIVE: To show that neck proprioceptive input can induce long-term effects on vestibular-dependent self-motion perception. METHODS: Motion perception was assessed by measuring the subject's error in tracking in the dark the remembered position of a fixed target during whole-body yaw asymmetric rotation of a supporting platform, consisting in a fast rightward half-cycle and a slow leftward half-cycle returning the subject to the initial position. Neck muscles were relaxed or voluntarily contracted, and/or vibrated. Whole-body rotation was administered during or at various intervals after the vibration train. The tracking position error (TPE) at the end of the platform rotation was measured during and after the muscle conditioning maneuvers. RESULTS: Neck input produced immediate and sustained changes in the vestibular perceptual response to whole-body rotation. Vibration of the left sterno-cleido-mastoideus (SCM) or right splenius capitis (SC) or isometric neck muscle effort to rotate the head to the right enhanced the TPE by decreasing the perception of the slow rotation. The reverse effect was observed by activating the contralateral muscle. The effects persisted after the end of SCM conditioning, and slowly vanished within several hours, as tested by late asymmetric rotations. The aftereffect increased in amplitude and persistence by extending the duration of the vibration train (from 1 to 10min), augmenting the vibration frequency (from 5 to 100Hz) or contracting the vibrated muscle. Symmetric yaw rotation elicited a negligible TPE, upon which neck muscle vibrations were ineffective. CONCLUSIONS: Neck proprioceptive input induces enduring changes in vestibular-dependent self-motion perception, conditional on the vestibular stimulus feature, and on the side and the characteristics of vibration and status of vibrated muscles. This shows that our perception of whole-body yaw-rotation is not only dependent on accurate vestibular information, but is modulated by proprioceptive information related to previously experienced position of head with respect to trunk. SIGNIFICANCE: Tonic proprioceptive inflow, as might occur as a consequence of enduring or permanent head postures, can induce adaptive plastic changes in vestibular-dependent motion sensitiveness. These changes might be counteracted by vibration of selected neck muscles.

Selective contribution of each hamstring muscle to anterior cruciate ligament protection and tibiofemoral joint stability in leg-extension exercise: a simulation study.

A biomechanical model was developed to simulate the selective effect of the co-contraction force provided by each hamstring muscle on the shear and compressive tibiofemoral joint reaction forces, during open kinetic-chain knee-extension exercises. This model accounts for instantaneous values of knee flexion angle [Formula: see text], angular velocity and acceleration, and for changes in magnitude, orientation, and application point of external resistance. The tibiofemoral shear force (TFSF) largely determines the tensile force on anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL). Biceps femoris is the most effective hamstring muscle in decreasing the ACL-loading TFSF developed by quadriceps contractions for [Formula: see text]. In this range, the semimembranosus generates the dominant tibiofemoral compressive force, which enhances joint stability, opposes anterior/posterior tibial translations, and protects cruciate ligaments. The semitendinosus force provides the greatest decreasing gradient of ACL-loading TFSF for [Formula: see text], and the greatest increasing gradient of tibiofemoral compressive force for [Formula: see text]. However, semitendinosus efficacy is strongly limited by its small physiological section. Hamstring muscles behave as a unique muscle in enhancing the PCL-loading TFSF produced by quadriceps contractions for [Formula: see text]. The levels of hamstrings co-activation that suppress the ACL-loading TFSF considerably shift when the knee angular acceleration is changed while maintaining the same level of knee extensor torque by a concurrent adjustment in the magnitude of external resistance. The knowledge of the specific role and the optimal activation level of each hamstring muscle in ACL protection and tibiofemoral stability are fundamental for planning safe and effective rehabilitative knee-extension exercises.

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature.

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K(+) channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here, we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during fatigue or ischemic insult.

Self-motion perception and vestibulo-ocular reflex during whole body yaw rotation in standing subjects: the role of head position and neck proprioception.

Self-motion perception and vestibulo-ocular reflex (VOR) were studied during whole body yaw rotation in the dark at different static head positions. Rotations consisted of four cycles of symmetric sinusoidal and asymmetric oscillations. Self-motion perception was evaluated by measuring the ability of subjects to manually track a static remembered target. VOR was recorded separately and the slow phase eye position (SPEP) was computed. Three different head static yaw deviations (active and passive) relative to the trunk (0°, 45° to right and 45° to left) were examined. Active head deviations had a significant effect during asymmetric oscillation: the movement perception was enhanced when the head was kept turned toward the side of body rotation and decreased in the opposite direction. Conversely, passive head deviations had no effect on movement perception. Further, vibration (100 Hz) of the neck muscles splenius capitis and sternocleidomastoideus remarkably influenced perceived rotation during asymmetric oscillation. On the other hand, SPEP of VOR was modulated by active head deviation, but was not influenced by neck muscle vibration. Through its effects on motion perception and reflex gain, head position improved gaze stability and enhanced self-motion perception in the direction of the head deviation.