Flexible motor sequence generation during stereotyped escape responses

Abstract

<jats:p>Complex animal behaviors arise from a flexible combination of stereotyped motor primitives. Here we use the escape responses of the nematode Caenorhabditis elegans to study how a nervous system dynamically explores the action space. The initiation of the escape responses is predictable: the animal moves away from a potential threat, a mechanical or thermal stimulus. But the motor sequence and the timing that follow are variable. We report that a feedforward excitation between neurons encoding distinct motor states underlies robust motor sequence generation, while mutual inhibition between these neurons controls the flexibility of timing in a motor sequence. Electrical synapses contribute to feedforward coupling whereas glutamatergic synapses contribute to inhibition. We conclude that C. elegans generates robust and flexible motor sequences by combining an excitatory coupling and a winner-take-all operation via mutual inhibition between motor modules.</jats:p>

Behavioral control by depolarized and hyperpolarized states of an integrating neuron by

“…Long reversals are more likely to be followed by an omega turn than short reversals (Chalasani et al, 2007; Croll, 1975; Gray et al, 2005; Huang et al, 2006; Wang et al, 2020; Zhao et al, 2003) (Figure 2F). The fraction of reversal omegas was reduced in tdc-1 mutants (Figure 2G, left), while pure reversals that terminate in an immediate forward run increased (Figure 2G, right).…”

“…RIM expresses 11 innexin genes, the most of any neuron (Bhattacharya et al, 2019). RIM gap junctions may depolarize AVA via innexins that are not affected by the unc-1(dn) transgene, such as inx-1 (Hori et al, 2018; Li et al, 2020; Wang et al, 2020). Cell-specific knockout of inx-1 and other innexins should provide deeper understanding of RIM gap junctions in AVA, AIB, AVE, and other neurons.…”

“…Many of its integrating interneurons and motor neurons are active during one or more of three basic motor behaviors – forward runs, reversals, and turns (Figure 1A). A set of interneurons including AIB, AVA, and RIM are active whenever animals reverse (Gordus et al, 2015; Kato et al, 2015; Nguyen et al, 2016; Venkatachalam et al, 2016); a different set, AIY, RIB, and AVB, are active during forward runs (Kaplan et al, 2020; Kato et al, 2015; Li et al, 2014; Nguyen et al, 2016); and a set including AIB, RIB, and RIV are active during sharp omega turns, which typically follow a reversal (Kato et al, 2015; Nguyen et al, 2016; Venkatachalam et al, 2016; Wang et al, 2020). The functional role of each integrating neuron can be evaluated by considering the neuron’s regulation of specific locomotor features, like reversal speed or turn angle, and its influence on locomotor transitions.…”

“…Other neurons in the locomotor circuit are implicated in transition dynamics. For example, altering AIB and RIB activity can change the probability and timing of the reversal-to-turn transition without generating abnormal pause states (Pokala et al, 2014, Wang et al, 2020).…”

“… (A) RIM synapses with interneurons, motor neurons, and muscle implicated in spontaneous foraging behavior (Cook et al, 2019; White et al, 1986). Colors of neurons indicate associated locomotor states based on neural manipulations and functional calcium imaging (Alkema et al, 2005; Gray et al, 2005; Kato et al, 2015; Li et al, 2014; Pokala et al, 2014; Steuer Costa et al, 2019; Wang et al, 2020; Zheng et al, 1999). …”