Abstract
SummaryLocomotion 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
The constituent neurons of neural networks, such as those controlling rhythmic locomotor behaviors, are connected by complex synaptic interactions and express a wide range of ion channels that regulate their intrinsic electrical properties
Larval Excitatory descending interneurons (dINs) Display Unique Properties The rhythmic output from central pattern generator (CPG) networks is usually driven by subpopulations of excitatory interneurons, which often have properties that distinguish them from other network neurons [31]
The dINs are the only neuron in the Xenopus swim network not to display an activity-dependent and Na/K-pump-mediated ultraslow afterhyperpolarization (usAHP) [22, 23]. To test whether these unique characteristics of dINs continue through development and to further reveal the role of dINs in locomotor rhythm generation, we examined dINs at the more mature larval stage 42 [34]
Summary
The constituent neurons of neural networks, such as those controlling rhythmic locomotor behaviors, are connected by complex synaptic interactions and express a wide range of ion channels that regulate their intrinsic electrical properties. These networks are influenced by an assortment of neuromodulators that target and modify specific ionic conductances and synaptic strengths. Ih plays a more complex role, being activated by precisely timed hyperpolarizing inputs, whose resulting activation generates a dynamic depolarization to provide an escape from inhibition that is critical to the rhythmicity of many pacemaker neuron types [4,5,6]. Through its effect on intrinsic properties, Ih currents can shorten the duration of incoming post-synaptic potentials (PSPs), which in turn facilitates precise integration [4,5,6]
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