AC. elegansneuron both promotes and suppresses motor behavior to fine tune motor output

Abstract

How neural circuits drive behavior is a central question in neuroscience. Proper execution of motor behavior requires the precise coordination of many neurons. Within a motor circuit, individual neurons tend to play discrete roles by promoting or suppressing motor output. How exactly neurons function in specific roles to fine tune motor output is not well understood. In C. elegans, the interneuron RIM plays important yet complex roles in locomotion behavior. Here, we show that RIM both promotes and suppresses distinct features of locomotion behavior to fine tune motor output. This dual function is achieved via the excitation and inhibition of the same motor circuit by electrical and chemical neurotransmission, respectively. Additionally, this bi-directional regulation contributes to motor adaptation in animals placed in novel environments. Our findings reveal that individual neurons within a neural circuit may act in opposing ways to regulate circuit dynamics to fine tune behavioral output.

Behavioral control by depolarized and hyperpolarized states of an integrating neuron

“…RIM glutamate might reinforce the reversal state by depolarizing AVA, while RIM tyramine inhibits the competing forward state via the tyramine-gated chloride channel LGC-55 on AVB ( Pirri et al, 2009 ). AVA also expresses a glutamate-gated chloride channel, avr-14, that inhibits spontaneous reversals; a genetic interaction between avr-14 and an RIM-specific knockdown of eat-4 suggests that this receptor could be a target of RIM glutamate ( Li et al, 2020 ). Since all of these receptors coexist in a circuit rich in positive and negative feedback ( Roberts et al, 2016 ), cell-specific knockouts of receptors as well as neurotransmitters may be needed to define their functions precisely.…”

“…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 ) , which synergizes with unc-9 to promote reversals evoked by optogenetic RIM depolarization ( Li et al, 2020 ). Similarly, the unc-1(dn ) transgene only partly suppresses the effects of RIM hyperpolarization on reversal frequency, suggesting that unc-9 may act with additional innexin subunits to propagate RIM hyperpolarization to AVA.…”

pOpsicle: An all-optical reporter system for synaptic vesicle recycling combining pH-sensitive fluorescent proteins with optogenetic manipulation of neuronal activity

“…The faster release and recycling in cholinergic neurons may be in line with their function in mediating locomotion, and the likely high SV turnover needed, while the slower release rate could be important to the dual role of RIM in regulating reversal behavior (Li et al, 2020;Sordillo and Bargmann, 2021). While RIM promotes reversals through activation of AVA and AVE neurons via gap junctions, glutamate signaling inhibits reversal probability by reducing the amplitude of Ca 2+ spikes within AVA and AVE (Li et al, 2020). A delayed release of glutamate from RIM may thus promote a fast reaction to noxious stimuli by initiation of reversals.…”

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

“…In addition, the AVB and RIB forward-promoting neurons express a number of inhibitory glutamate-gated chloride channels (GluCls), and inhibition of AVB could be a site of RIM glutamate-tyramine convergence (Brockie & Maricq, 2006; Dent et al, 2000; Taylor et al, 2019). However, AIB, AVA, and RIM also express GluCls that regulate reversals (Li et al, 2020), and RIM expresses LGC-55 (Taylor et al, 2019). Since all of these receptors co-exist in a circuit rich in positive and negative feedback (Roberts et al, 2016), cell-specific knockouts of receptors as well as neurotransmitters may be needed to define their functions precisely.…”

“…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.…”