Passive limb training modulates respiratory rhythmic bursts

Abstract

Exercise modifies respiratory functions mainly through the afferent feedback provided by exercising limbs and the descending input from suprapontine areas, two contributions that are still underestimated in vitro. To better characterize the role of limb afferents in modulating respiration during physical activity, we designed a novel experimental in vitro platform. The whole central nervous system was isolated from neonatal rodents and kept with hindlimbs attached to an ad-hoc robot (Bipedal Induced Kinetic Exercise, BIKE) driving passive pedaling at calibrated speeds. This setting allowed extracellular recordings of a stable spontaneous respiratory rhythm for more than 4 h, from all cervical ventral roots. BIKE reversibly reduced the duration of single respiratory bursts even at lower pedaling speeds (2 Hz), though only an intense exercise (3.5 Hz) modulated the frequency of breathing. Moreover, brief sessions (5 min) of BIKE at 3.5 Hz augmented the respiratory rate of preparations with slow bursting in control (slower breathers) but did not change the speed of faster breathers. When spontaneous breathing was accelerated by high concentrations of potassium, BIKE reduced bursting frequency. Regardless of the baseline respiratory rhythm, BIKE at 3.5 Hz always decreased duration of single bursts. Surgical ablation of suprapontine structures completely prevented modulation of breathing after intense training. Albeit the variability in baseline breathing rates, intense passive cyclic movement tuned fictive respiration toward a common frequency range and shortened all respiratory events through the involvement of suprapontine areas. These observations contribute to better define how the respiratory system integrates sensory input from moving limbs during development, opening new rehabilitation perspectives.

A focal traumatic injury to the spinal cord causes an immediate and massive spreading depolarization sustained by chloride ions, with transient network dysfunction and remote cortical glia changes

“…Spontaneous rhythmic motor discharges recorded from cervical VRs, with a period of 24.27 ± 16.13 s, were attributed to respiratory bursts that were also derived synchronous among bilateral lumbar VRs (Mohammadshirazi et al, 2023;Apicella and Taccola, 2023). The coefficient of variation (CV), an indicator of response consistency, was determined by the ratio between standard deviation and mean value (Taccola et al, 2020).…”

“…Furthermore, in the same sample experiment, spontaneous rhythmic bursts (0.02 ± 0.01 Hz) originating from respiratory networks in the brainstem (Mohammadshirazi et al, 2023;Apicella and Taccola, 2023) were simultaneously recorded in control from cervical and lumbar VRs (Fig. 4 C, left).…”

“…To monitor the respiratory rhythm originated by neuronal networks located in the brainstem (Del Negro et al, 2018), spontaneous rhythmic bursts were recorded from cervical VRs of the isolated CNS (Mohammadshirazi et al, 2023;Apicella and Taccola, 2023). The respiratory rhythm can also be recorded from lumbar VRs, which drive the recruitment of chest muscles to assist the expiratory phase (Giraudin et al, 2008).…”

“…This temporal limitation sums up to the effects of anesthetics that depress neuronal excitability and are used in preclinical models at the time of the physical trauma. A solution to avoid any technical artifacts, as well as any consequences of anesthetics, is the adoption of the neonatal preparation of the entire central nervous system in vitro (CNS; (Mohammadshirazi et al, 2023;Apicella and Taccola, 2023)), which does not require the administration of any drugs. In addition, the rodent spinal cord can be optimally damaged through a low-noise calibrated micro impactor recently designed in the laboratory.…”