Chronic exercise increases excitability of lamina X neurons through enhancement of persistent inward currents and dendritic development in mice

Chronic exercise has been shown to enhance excitability of spinal interneurons in rodents. However, the mechanisms underlying this enhancement remain unclear. In this study we investigated adaptability of lamina X neurons with 3-week treadmill exercise in mice of P21-P24. Whole-cell patch-clamp recording was performed on the interneurons from slices of T12-L4. The experimental results included the following. (1) Treadmill exercise reduced rheobase by 7.4 ± 2.2 pA (control: 11.3 ± 6.1 pA, n = 12; exercise: 3.8 ± 4.6 pA, n = 13; P = 0.002) and hyperpolarized voltage threshold by 7.1 ± 1.5 mV (control: -36.6 ± 4.6 mV, exercise: -43.7 ± 2.7 mV; P = 0.001). (2) Exercise enhanced persistent inward currents (PICs) with increase of amplitude (control: 140.6 ± 56.3 pA, n = 25; exercise: 225.9 ± 62.5 pA, n = 17; P = 0.001) and hyperpolarization of onset voltage (control: -50.3 ± 3.6 mV, exercise: -56.5 ± 5.5 mV; P = 0.001). (3) PICs consisted of dihydropyridine-sensitive calcium (Ca-PIC) and tetrodotoxin-sensitive sodium (Na-PIC) components. Exercise increased amplitude of both components but hyperpolarized onset voltage of Na-PIC only. (4) Exercise reduced derecruitment current of repetitive firing evoked by a current bi-ramp and prolonged firing in the falling phase of the bi-ramp. The derecruitment reduction was eliminated by bath application of 3 μM riluzole or 25 μM nimodipine, suggesting that both Na-PIC and Ca-PIC contributed to the exercise-prolonged hysteresis of firing. (5) Exercise facilitated dendritic development with significant increase in dendritic length by 285.1 ± 113 μm (control: 457.8 ± 171.8 μm, n = 12; exercise: 742.9 ± 357 μm, n = 14; P = 0.019). We concluded that 3-week treadmill exercise increased excitability of lamina X interneurons through enhancement of PICs and increase of dendritic length. This study provided insight into cellular and channel mechanisms underlying adaptation of the spinal motor system in exercise. KEY POINTS: Chronic exercise alters adaptability of the spinal motor system in rodents; multiple mechanisms are responsible for the adaptation, including regulation of neuronal excitability and change in dendritic morphology. Spinal interneurons in lamina X are a cluster of heterogeneous neurons playing multifunctional roles in the spinal cord; chronic exercise in juvenile mice increased excitability of these interneurons and facilitated dendritic development. Lamina X neurons expressed persistent inward currents (PICs) with calcium (Ca-PIC) and sodium (Na-PIC) components; the exercise-increased excitability of lamina X neurons was mediated by enhancing the Ca-PIC and Na-PIC components and increasing dendritic length. This study unveiled novel morphological and ionic mechanisms underlying adaptation of lamina X neurons in rodents during chronic exercise.