Control of Xenopus Tadpole Locomotion via Selective Expression of Ih in Excitatory Interneurons

Summary Locomotion relies on the coordinated activity of rhythmic neurons in the hindbrain and spinal cord and depends critically on the intrinsic properties of excitatory interneurons. Therefore, understanding how ion channels sculpt the properties of these interneurons, and the consequences for circuit function and behavior, is an important task. The hyperpolarization-activated cation current, Ih, is known to play important roles in shaping neuronal properties and for rhythm generation in many neuronal networks. We show in stage 42 Xenopus laevis frog tadpoles that Ih is strongly expressed only in excitatory descending interneurons (dINs), an important ipsilaterally projecting population that drives swimming activity. The voltage-dependent HCN channel blocker ZD7288 completely abolished a prominent depolarizing sag potential in response to hyperpolarization, the hallmark of Ih, and hyperpolarized dINs. ZD7288 also affected dIN post-inhibitory rebound firing, upon which locomotor rhythm generation relies, and disrupted locomotor output. Block of Ih also unmasked an activity-dependent ultraslow afterhyperpolarization (usAHP) in dINs following swimming, mediated by a dynamic Na/K pump current. This usAHP, unmasked in dINs by ZD7288, resulted in suprathreshold stimuli failing to evoke swimming at short inter-swim intervals, indicating an important role for Ih in maintaining swim generation capacity and in setting the post-swim refractory period of the network. Collectively, our data suggest that the selective expression of Ih in dINs determines specific dIN properties that are important for rhythm generation and counteracts an activity-dependent usAHP to ensure that dINs can maintain coordinated swimming over a wide range of inter-swim intervals.
Highlights • Ih is strongly expressed in Xenopus locomotor-rhythm-generating dIN interneurons • Ih is active at rest in dINs, contributing to their distinct electrical properties • dINs normally lack a Na pump-dependent ultra-slow afterhyperpolarization (usAHP) • Ih counterbalances dIN usAHPs to preserve tadpole rhythm generating capacity
Picton et al. reveal that a hyperpolarization-activated current, Ih, selectively affects the electrical properties of locomotor rhythm generating interneurons in the Xenopus tadpole spinal motor circuit. By counterbalancing a dynamic hyperpolarizing Na pump current, Ih preserves rhythm generating capacity at short inter-swim intervals.