A mechanism for graded motor control encoded in the channel properties of the muscle ACh receptor

Abstract

The larva of the invertebrate chordate Ciona intestinalis possesses only 36 striated muscle cells and lacks body segmentation. It can swim, however, like a vertebrate tadpole, and how its simple body achieves such sophisticated motor control remains puzzling. We found that muscle contractions in Ciona larvae are variable and can be changed by sensory stimuli, so that neuromuscular transmission can convert the variable neural inputs into graded muscle activity. We characterized the molecular nature of the nicotinic acetylcholine receptor (nAChR) at neuromuscular synapses. When heterologously expressed in Xenopus oocytes, this nAChR channel exhibited two biophysical features resembling vertebrate neuronal nAChRs rather than the muscle type: inward rectification and high Ca 2+ permeability. Both of these properties were abolished by a simple mutation at the channel pore in one of the non-α subunits, called BGDE3, so as to adopt the sequence of related subunits in vertebrates, γ and ε. In vivo exchange of native BGDE3 with this mutant severely disrupted graded motor control, producing instead sporadic all-or-none-like flexions. The graded nature of excitation-contraction (E-C) coupling in this organism is based on the traits of the nAChR channel pore, which confer fine controllability on such a coarse motor architecture.ascidian larva | muscle physiology | locomotion | neuromuscular junction I n tailed aquatic vertebrates such as fish and amphibian tadpoles, swimming undulations are generated by sequential activation of the myotomal segments. These segments contain multiple classes of muscle fibers, including slow, fast, and intermediate types, with distinct mechanical and metabolic properties that constitute a "gearing" system adjustable to a wide range of speeds. The activity of a given segment is mostly independent of the others, and when, which, and how many fibers will be activated are determined by a neural network in the spinal cord (1-3). This neural mechanism by which contraction magnitude is varied is based on the logic for recruiting motor neurons into the active population, called the size principle (1-4). This control system for compound muscle fibers is likely a key innovation in vertebrates, but how far this basis can be traced back in invertebrate systems is poorly understood.Ascidians are marine invertebrates that constitute a sister clade of the vertebrates (5, 6). The larva of the ascidian Ciona intestinalis (L) is tadpole shaped and possesses bilateral muscle bands, a dorsal neural tube supported by an axial notochord, and sensory organs including a photoreceptive ocellus (Fig. 1A and Fig. S1A). Despite this suite of organs, the body of the Ciona larva is quite simple. The muscle band on each side lacks a segmental plan and is composed of only 18 cells arranged in a single layer (Fig. 1A and Fig. S1). The 4-5 pairs of cholinergic motor neurons located in the motor ganglion (or the visceral ganglion) have accounted for the swimming behavior (Fig. S1) (7-10). These cholinergic neurons project axons...

Modification of the larval swimming behavior in Oikopleura dioica, a chordate with a miniaturized central nervous system by dsRNA injection into fertilized eggs

“…The strong but partial paralysis of Oikopleura observed following ChAT/VAChT knockdown supports the current assumption that excitatory neuromuscular transmission in tunicates is cholinergic as in vertebrates (Ohmori and Sasaki, , Søviknes et al, Nishino et al, ), although there is also immunohistochemical evidence for a neuromuscular function of GABA (Bollner et al, , and see below). A significant drop of acetylcholine production and vesicular storage is expected from the observed fourfold reduction of ChAT transcripts and twofold reduction of VAChT transcripts.…”

Cellular identity and Ca2+signaling activity of the non-reproductive GnRH system in theCionalarva

“…In this study, we identified cell types of gnrh2-expressing cells and visualized their activity in the Ciona larva. Previously, the cells expressing GnRH-encoding genes had been only partially Cholinergic neurons in the motor ganglion have been implicated in the regulation of tail muscle contraction (Horie et al 2010;Nishino et al 2010Nishino et al , 2011Kusakabe 2017). Here we show that one subtype of cholinergic neurons in the motor ganglion expresses gnrh2 (Fig.…”

Ascidians as excellent chordate models for studying the development of the nervous system during embryogenesis and metamorphosis

“…; Nishino et al . , ). Improvements in the functional analyses of neurons have been reported in model organisms for which transgenes are devised for visualizing and controlling the physiology of neurons, as exemplified by calcium indicators, neurotoxins and optogenetic tools (Sweeney et al .…”