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Persistent sodium currents (INaP) are common in neuronal circuitries and have been implicated in several diseases, such as amyotrophic lateral sclerosis (ALS) and epilepsy. However, the role of INaP in the regulation of specific behaviors is still poorly understood. In this study we have characterized INaP and investigated its role in the swimming and struggling behavior of Xenopus tadpoles. INaP was identified in three groups of neurons, namely, sensory Rohon-Beard neurons (RB neurons), descending interneurons (dINs), and non-dINs (neurons rhythmically active in swimming). All groups of neurons expressed INaP, but the currents differed in decay time constants, amplitudes, and the membrane potential at which INaP peaked. Low concentrations (1 µM) of the INaP blocker riluzole blocked INaP ~30% and decreased the excitability of the three neuron groups without affecting spike amplitudes or cellular input resistances. Riluzole reduced the number of rebound spikes in dINs and depressed repetitive firing in RB neurons and non-dINs. At the behavior level, riluzole at 1 µM shortened fictive swimming episodes. It also reduced the number of action potentials neurons fired on each struggling cycle. The results show that INaP may play important modulatory roles in motor behaviors.NEW & NOTEWORTHY We have characterized persistent sodium currents in three groups of spinal neurons and their role in shaping spiking activity in the Xenopus tadpole. We then attempted to evaluate the role of persistent sodium currents in regulating tadpole swimming and struggling motor outputs by using low concentrations of the persistent sodium current antagonist riluzole.
Fig. 1. Measurements of INaT and INaP in spinal neurons. A: voltage ramp in an RB neuron reveals INaP. B: current-voltage (I-V) curve of INaP in RB neurons measured from the ramp currents (n = 8). C: sodium currents in an RB neuron evoked by a voltage step to −10 mV. The thick gray curve shows the double-exponential fitting of the decay of the currents. D: I-V curves of INaT in RB neurons, dINs, and non-dINs. E: decay time constants of the INaT at steps to different voltages in the 3 neuron groups. F: single-exponential fitting (thick gray curve) of the slowly decaying currents. Dotted line indicates estimation of INaP at the peak of combined sodium currents. G: ratios of INaP to INaT in RB neurons, dINs, and non-dINs. H: current densities for INaT and INaP in RB neurons, dINs, and non-dINs. **P < 0.01.
Fig. 2. Properties of INaP in the 3 neuron groups and the effect of riluzole. A–C: sodium currents in an RB neuron (A), a dIN (B), and a non-dIN (C) in response to voltage step to −40 (black traces), −10, or 0 mV (red traces showing the maximal INaP) and to 30 mV (blue traces). D: averaged I-V curves for the INaP in RB neurons, dINs, and non-dINs. E: decay time constants of INaP at steps to different membrane potentials in RB neurons, dINs, and non-dINs. F: effect of 1 µM riluzole on INaP in an RB neuron. G: blocking effects of 1, 10, and 20 µM riluzole on INaP. H: effect of 1 µM riluzole on INaT in an RB neuron. I: effect of 1, 10, and 20 µM on INaT. *P < 0.05; **P < 0.01.
Fig. 3. Effects of riluzole on firing properties of the 3 different neuron groups. A1: effect of 1 µM riluzole on the rebound firing in a dIN. A2: bar chart summarizing the reduction of rebound spikes in dINs (n = 6). A3: subthreshold depolarization and firing at threshold level in a dIN in control (left), 1 µM riluzole (**P < 0.01; middle), and wash (right). B1: effect of riluzole on an RB neuron with slow, repetitive firing. B2: bar chart showing the reduction of spikes by riluzole (n = 3). B3: subthreshold depolarization and firing at threshold level in an RB neuron in control (left), 1 µM riluzole (middle), and wash (right). C1: effect of riluzole on the repetitive spiking in a non-dIN. C2: reduction of number of spikes by riluzole (n = 9). C3: subthreshold depolarization and firing at threshold in a non-dIN in control (left), 1 µM riluzole (middle), and wash (right). D: effect of riluzole on the spike thresholds in RB neurons (n = 6), dINs (n = 4), and non-dINs (n = 5). *P < 0.05; **P < 0.01; ***P < 0.001. E: lack of effects of riluzole on spike amplitudes in RB neurons, dINs, and non-dINs. F: lack of effects of riluzole on input resistances in RB neurons, dINs, and non-dINs.
Fig. 4. Effects of 1 µM riluzole on fictive swimming and struggling. A: motor nerve (m.n.) recordings during swimming evoked by light dimming in control, 1 µM riluzole, and after washout. B: reduction of the swimming episode duration by 1 µM riluzole (n = 5; *P < 0.05). C: effects of riluzole on the number of spikes on each struggling cycle. Dashed gray lines indicate periods of repetitive skin stimulation at the rostral trunk (40 pulses at 30 Hz), used to evoke fictive struggling. l.m.n., motor nerve recording from left side; l.aIN, ascending interneuron recording from left side. D: riluzole does not affect the firing reliability of neurons in swimming (% of cycles with spiking). E: riluzole reduces the number of spikes per struggling cycle (*P < 0.05). F: struggling frequencies are not affected by riluzole.
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