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

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.

Intrinsic temporal tuning of neurons in the optic tectum is shaped by multisensory experience

“…Dysregulation of intrinsic plasticity affects the network dynamics (Tien and Kerschensteiner, 2018), and can lead to a loss of function (Marcelin et al, 2009). And yet, with the possible exception of oscillatory networks (Marder and Taylor, 2011;Picton et al, 2018), the exact ways in which intrinsic plasticity contributes to network tuning, remain unclear. We know that neurons adjust their spikiness to match the levels of synaptic activation they experience (Aizenman et al, 2003;Titley et al, 2017), but we also know that intrinsic properties can affect more subtle neuronal tuning to different temporal patterns of activation (Azouz and Gray, 2000;Branco et al, 2010;Fontaine et al, 2014;Jarvis et al, 2018;Ohtsuki and Hansel, 2018;Zbili et al, 2019).…”

Contributions of h- and Na+/K+pump currents to the generation of episodic and continuous rhythmic activities

“…The model was a single CPG composed of two inhibitory half centres, with IPump, Ih, and INaP currents. We derived these parameters from insights based on studies on the dynamic roles of the IPump in the regulation of the leech heartbeat (Kueh et al, 2016;Tobin and Calabrese, 2005) and Xenopus tadpole locomotor CPGs (Picton et al, 2018;Zhang et al, 2015;Zhang and Sillar, 2012).…”

“…Similarly, in the Xenopus tadpole spinal cord CPG, Ih is expressed only in glutamatergic rhythmgenerating interneurons (dINs), where it opposes and cancels out the inhibitory IPump. Further, blockade of Ih disrupts STMM (Picton et al, 2018), suggesting that a balance between IPump and Ih is required for STMM. IPump also interacts with Ih in leech heartbeat neurons, which accounts for the paradoxical speeding up of the rhythm when IPump is increased experimentally with monensin (Kueh et al, 2016).…”

“…Ih plays an important role in a variety of rhythmic networks in both invertebrate (Angstadt and Calabrese, 1989;Peck et al, 2006) and vertebrate systems (Butt et al, 2002;Kjaerulff and Kiehn, 2001;Smith and Perrier, 2006;Takahashi, 1990;Thoby-Brisson and Ramirez, 2000) and dynamically interacts with IPump (Kueh et al, 2016;Picton et al, 2018;Tobin and Calabrese, 2005;Zhang et al, 2017). Leech heart single neuron and HCO studies demonstrated episodic bursting patterns at low IPumpMax strengths (Cymbalyuk, unpublished data).…”

“…The IPump supports homeostatic and dynamic functions based on the varying sensitivities of the alpha-1 and alpha-3 subunits to intracellular Na + concentrations. On the single-cell level, dynamic pump action is linked to the alpha-3 subunit and leads to an usAHP following the intense firing of action potentials (Picton et al, 2018(Picton et al, , 2017Pulver and Griffith, 2010;Tiwari et al, 2018;Zhang et al, 2015;Zhang and Sillar, 2012). In the spinal cord, the usAHP of the membrane potential determines future activity based on past neuronal activity, creating short term motor memory (STMM; Picton et al, 2017;Zhang et al, 2015;Zhang and Sillar, 2012).…”