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Objective: To examine the role of vestibular inputs on respiratory and oromotor systems in healthy preterm infants. Study Design: A total of 27 preterm infants were quasi-randomly assigned to either the VestibuGlide treatment or control groups. VestibuGlide infants were held in a developmentally supportive position, given a pacifier and received a series of vestibular stimuli, counterbalanced across rate and acceleration conditions, 15 min 3 times per day for 10 days. The control infants were also held in a developmentally supportive position, given a pacifier for 15 min 3 times per day for 10 days but did not receive the VestibuGlide stimulation. Result: A multi-level regression model revealed that treatment infants increased their respiratory rate in response to vestibular stimulus, and that the highest level of vestibular acceleration delivered to the infants (0.51 ms −2 ) resulted in a significant increase in breaths per minute. Conclusion: Vestibular stimulation delivered to preterm infants before scheduled feeds effectively modulates respiratory rate and resets the respiratory central pattern generator.

Breathing is a well-described, vital and surprisingly complex behaviour, with behavioural and physiological outputs that are easy to directly measure. Key neural elements for generating breathing pattern are distinct, compact and form a network amenable to detailed interrogation, promising the imminent discovery of molecular, cellular, synaptic and network mechanisms that give rise to the behaviour. Coupled oscillatory microcircuits make up the rhythmic core of the breathing network. Primary among these is the preBötzinger Complex (preBötC), which is composed of excitatory rhythmogenic interneurons and excitatory and inhibitory pattern-forming interneurons that together produce the essential periodic drive for inspiration. The preBötC coordinates all phases of the breathing cycle, coordinates breathing with orofacial behaviours and strongly influences, and is influenced by, emotion and cognition. Here, we review progress towards cracking the inner workings of this vital core.

The central pattern generator (CPG) for locomotion is a set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current ( I NaP ). How they proceed to regulate the locomotor rhythm remained unknown. Here, in neonatal rodents, we identified a persistent potassium current critical in regulating pacemakers and locomotion speed. This current recapitulates features of the M-current ( I M ): a subthreshold noninactivating outward current blocked by 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) and enhanced by N -(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide (ICA73). Immunostaining and mutant mice highlight an important role of Kv7.2-containing channels in mediating I M . Pharmacological modulation of I M regulates the emergence and the frequency regime of both pacemaker and CPG activities and controls the speed of locomotion. Computational models captured these results and showed how an interplay between I M and I NaP endows the locomotor CPG with rhythmogenic properties. Overall, this study provides fundamental insights into how I M and I NaP work in tandem to set the speed of locomotion.

Lumbar central pattern generators (CPGs) control the basic rhythm and coordinate muscle activation underlying hindlimb locomotion in quadrupedal mammals. The existence and function of CPGs in humans have remained controversial. Here, we investigated a case of a male individual with complete thoracic spinal cord injury who presented with a rare form of self-sustained rhythmic spinal myoclonus in the legs and rhythmic activities induced by epidural electrical stimulation (EES). Analysis of muscle activation patterns suggested that the myoclonus tapped into spinal circuits that generate muscle spasms, rather than reflecting locomotor CPG activity as previously thought. The EES-induced patterns were fundamentally different in that they included flexor-extensor and left-right alternations, hallmarks of locomotor CPGs, and showed spontaneous errors in rhythmicity. These motor deletions, with preserved cycle frequency and period when rhythmic activity resumed, were previously reported only in animal studies and suggest a separation between rhythm generation and pattern formation. Spinal myoclonus and the EES-induced activity demonstrate that the human lumbar spinal cord contains distinct mechanisms for generating rhythmic multi-muscle patterns. The existence of dedicated spinal circuits generating locomotion in humans has remained controversial. Here, the authors study distinct forms of spontaneous and induced rhythmic leg activity in a paralyzed individual, providing insight into spinal rhythmogenesis and pattern formation.

The striking similarity between biological locomotion gaits and the evolution of phase patterns in coupled oscillatory network can be traced to the role of central pattern generator located in the spinal cord. Bio-inspired robotics aim at harnessing this control approach for generation of rhythmic patterns for synchronized limb movement. Here, we utilize the phenomenon of synchronization and emergent spatiotemporal pattern from the interaction among coupled oscillators to generate a range of locomotion gait patterns. We experimentally demonstrate a central pattern generator network using capacitively coupled Vanadium Dioxide nano-oscillators. The coupled oscillators exhibit stable limit-cycle oscillations and tunable natural frequencies for real-time programmability of phase-pattern. The ultra-compact 1 Transistor-1 Resistor implementation of oscillator and bidirectional capacitive coupling allow small footprint area and low operating power. Compared to biomimetic CMOS based neuron and synapse models, our design simplifies on-chip implementation and real-time tunability by reducing the number of control parameters. Designing alternative paradigms for bio-inspired analog computing that harnesses collective dynamics remains a challenge. Here, the authors exploit the synchronization dynamics of coupled vanadium dioxide-based insulator-to-metal phase-transition nano-oscillators for adaptive locomotion control.

The mechanisms underlying the mammalian ultradian sleep rhythm—the alternation of rapid-eye-movement (REM) and slow-wave (SW) states—are not well understood but probably depend, at least in part, on circuits in the brainstem 1 , 2 , 3 , 4 , 5 – 6 . Here, we use perturbation experiments to probe this ultradian rhythm in sleeping lizards ( Pogona vitticeps ) 7 , 8 – 9 and test the hypothesis that it originates in a central pattern generator 10 , 11 —circuits that are typically susceptible to phase-dependent reset and entrainment by external stimuli 12 . Using light pulses, we find that Pogona ’s ultradian rhythm 8 can be reset in a phase-dependent manner, with a critical transition from phase delay to phase advance in the middle of SW. The ultradian rhythm frequency can be decreased or increased, within limits, by entrainment with light pulses. During entrainment, Pogona REM (REM P ) can be shortened but not lengthened, whereas SW can be dilated more flexibly. In awake animals, a few alternating light/dark epochs matching natural REM P and SW durations entrain a sleep-like brain rhythm, suggesting the transient activation of an ultradian rhythm generator. In sleeping animals, a light pulse delivered to a single eye causes an immediate ultradian rhythm reset, but only of the contralateral hemisphere; both sides resynchronize spontaneously, indicating that sleep is controlled by paired rhythm-generating circuits linked by functional excitation. Our results indicate that central pattern generators of a type usually known to control motor rhythms may also organize the ultradian sleep rhythm in a vertebrate. Central pattern generators of a type usually known to control motor rhythms may also organize vertebrate ultradian sleep rhythm.

Efficient searching for resources such as food by animals is key to their survival. It has been proposed that diverse animals from insects to sharks and humans adopt searching patterns that resemble a simple Lévy random walk, which is theoretically optimal for ‘blind foragers’ to locate sparse, patchy resources. To test if such patterns are generated intrinsically, or arise via environmental interactions, we tracked free-moving Drosophila larvae with (and without) blocked synaptic activity in the brain, suboesophageal ganglion (SOG) and sensory neurons. In brain-blocked larvae, we found that extended substrate exploration emerges as multi-scale movement paths similar to truncated Lévy walks. Strikingly, power-law exponents of brain/SOG/sensory-blocked larvae averaged 1.96, close to a theoretical optimum (µ ≅ 2.0) for locating sparse resources. Thus, efficient spatial exploration can emerge from autonomous patterns in neural activity. Our results provide the strongest evidence so far for the intrinsic generation of Lévy-like movement patterns.

Underwater walking is one of the most common hydrotherapeutic exercises. Therefore, understanding muscular control during underwater walking is important for optimizing training regimens. The effects of the water environment on walking are mainly related to the hydrostatic and hydrodynamic theories of buoyancy and drag force. To date, muscular control during underwater walking has been investigated at the individual muscle level. However, it is recognized that the human nervous system modularly controls multiple muscles through muscle synergies, which are sets of muscles that work together. We found that the same set of muscle synergies was shared between the two walking tasks. However, some task-dependent modulation was found in the activation combination across muscles and temporal activation patterns of the muscle synergies. The results suggest that the human nervous system modulates activation of lower-limb muscles during water walking by finely tuning basic locomotor muscle synergies that are used during land walking to meet the biomechanical requirements for walking in the water environment.

Within the cervical and lumbar spinal enlargements, central pattern generator (CPG) circuitry produces the rhythmic output necessary for limb coordination during locomotion. Long propriospinal neurons that inter-connect these CPGs are thought to secure hindlimb-forelimb coordination, ensuring that diagonal limb pairs move synchronously while the ipsilateral limb pairs move out-of-phase during stepping. Here, we show that silencing long ascending propriospinal neurons (LAPNs) that inter-connect the lumbar and cervical CPGs disrupts left-right limb coupling of each limb pair in the adult rat during overground locomotion on a high-friction surface. These perturbations occurred independent of the locomotor rhythm, intralimb coordination, and speed-dependent (or any other) principal features of locomotion. Strikingly, the functional consequences of silencing LAPNs are highly context-dependent; the phenotype was not expressed during swimming, treadmill stepping, exploratory locomotion, or walking on an uncoated, slick surface. These data reveal surprising flexibility and context-dependence in the control of interlimb coordination during locomotion.

The presence of synchronized clusters in neuron networks is a hallmark of information transmission and processing. Common approaches to study cluster synchronization in networks of coupled oscillators ground on simplifying assumptions, which often neglect key biological features of neuron networks. Here we propose a general framework to study presence and stability of synchronous clusters in more realistic models of neuron networks, characterized by the presence of delays, different kinds of neurons and synapses. Application of this framework to two examples with different size and features (the directed network of the macaque cerebral cortex and the swim central pattern generator of a mollusc) provides an interpretation key to explain known functional mechanisms emerging from the combination of anatomy and neuron dynamics. The cluster synchronization analysis is carried out also by changing parameters and studying bifurcations. Despite some modeling simplifications in one of the examples, the obtained results are in good agreement with previously reported biological data.