An Imbalancing Act: Gap Junctions Reduce the Backward Motor Circuit Activity to Bias C. elegans for Forward Locomotion

Abstract

A neural network can sustain and switch between different activity patterns to execute multiple behaviors. By monitoring the decision making for directional locomotion through motor circuit calcium imaging in behaving Caenorhabditis elegans (C. elegans), we reveal that C. elegans determines the directionality of movements by establishing an imbalanced output between the forward and backward motor circuits and that it alters directions by switching between these imbalanced states. We further demonstrate that premotor interneurons modulate endogenous motoneuron activity to establish the output imbalance. Specifically, the UNC-7 and UNC-9 innexin-dependent premotor interneuron-motoneuron coupling prevents a balanced output state that leads to movements without directionality. Moreover, they act as shunts to decrease the backward-circuit activity, establishing a persistent bias for the high forward-circuit output state that results in the inherent preference of C. elegans for forward locomotion. This study demonstrates that imbalanced motoneuron activity underlies directional movement and establishes gap junctions as critical modulators of the properties and outputs of neural circuits.

Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans

“…Nuclear recordings were successfully used previously in two whole-brain imaging studies of anesthetized and immobilized C. elegans, and those works argue that nuclear calcium levels capture the calcium dynamics of the rest of the neuron (11,12). Recordings from the cell body are the most prevalent in the literature and have previously been used to study activity of a number of neurons relating to locomotory behavior (17,18,(25)(26)(27)(28). Because C. elegans nuclei are thought to be porous to calcium and because the nuclei take up a large portion of the cell body, nuclear recordings used here likely capture calcium transients observed in the cell body.…”

“…24 and and then developing rapidly (17,18,(25)(26)(27)(28)(29). One limitation of these freely moving calcium imaging systems is that they are limited to imaging only a very small subset of neurons and lack the ability to distinguish neurons that lie atop one another in the axial direction of the microscope.…”

Pan-neuronal imaging in roaming Caenorhabditis elegans

“…The nematode Caenorhabditis elegans is particularly ideal for optical neurophysiology owing to its small size, optical transparency, compact nervous system, and ease of genetic manipulation. Imaging systems for tracking the activity of small numbers of neurons have been effective in determining their role during nematode locomotion and navigational behaviors like chemotaxis, thermotaxis, and the escape response (1)(2)(3)(4)(5)(6).…”

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

“…In addition, the anatomical wiring diagram of the C. elegans nervous system derived from electron micrographs has ∼600 gap junctions among its 302 neurons, representing about 10% of all synapses (16)(17)(18)(19). Circuit manipulations and genetic studies indicate that gap junctions are essential in locomotion circuits and escape behaviors (20,21). For example, the broadly expressed innexin subunits unc-7 and unc-9 are required for coordinated locomotion and link command interneurons with motor neurons to balance forward and backward movement states (21,22), and unc-7 also mediates electrical coupling between neurons in the gap junction circuit for nose-touch avoidance behavior (23).…”

“…Circuit manipulations and genetic studies indicate that gap junctions are essential in locomotion circuits and escape behaviors (20,21). For example, the broadly expressed innexin subunits unc-7 and unc-9 are required for coordinated locomotion and link command interneurons with motor neurons to balance forward and backward movement states (21,22), and unc-7 also mediates electrical coupling between neurons in the gap junction circuit for nose-touch avoidance behavior (23). However, most neuronal gap junctions are solely predicted by electron micrographs and have not been linked to particular genes or functions.…”