NPR-9, a Galanin-Like G-Protein Coupled Receptor, and GLR-1 Regulate Interneuronal Circuitry Underlying Multisensory Integration of Environmental Cues in Caenorhabditis elegans

Abstract

C. elegans inhabit environments that require detection of diverse stimuli to modulate locomotion in order to avoid unfavourable conditions. In a mammalian context, a failure to appropriately integrate environmental signals can lead to Parkinson’s, Alzheimer’s, and epilepsy. Provided that the circuitry underlying mammalian sensory integration can be prohibitively complex, we analyzed nematode behavioral responses in differing environmental contexts to evaluate the regulation of context dependent circuit reconfiguration and sensorimotor control. Our work has added to the complexity of a known parallel circuit, mediated by interneurons AVA and AIB, that integrates sensory cues and is responsible for the initiation of backwards locomotion. Our analysis of the galanin-like G-protein coupled receptor NPR-9 in C. elegans revealed that upregulation of galanin signaling impedes the integration of sensory evoked neuronal signals. Although the expression pattern of npr-9 is limited to AIB, upregulation of the receptor appears to impede AIB and AVA circuits to broadly prevent backwards locomotion, i.e. reversals, suggesting that these two pathways functionally interact. Galanin signaling similarly plays a broadly inhibitory role in mammalian models. Moreover, our identification of a mutant, which rarely initiates backwards movement, allowed us to interrogate locomotory mechanisms underlying chemotaxis. In support of the pirouette model of chemotaxis, organisms that did not exhibit reversal behavior were unable to navigate towards an attractant peak. We also assessed ionotropic glutamate receptor GLR-1 cell-specifically within AIB and determined that GLR-1 fine-tunes AIB activity to modify locomotion following reversal events. Our research highlights that signal integration underlying the initiation and fine-tuning of backwards locomotion is AIB and NPR-9 dependent, and has demonstrated the suitability of C. elegans for analysis of multisensory integration and sensorimotor control.

The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons

“…Many of these unc-42- dependent neuropeptides and neuropeptide receptors have been previously shown to be involved in locomotory behavior, and we found that these behavioral defects match subsets of the defects observed in unc-42 mutants. For example, animals lacking flp-18, nlp-15, npr-9, and npr-11 display decreased backwards motion (i.e., decreased reversals) ( Bhardwaj et al, 2018 ; Campbell et al, 2016 ; Chalasani et al, 2010 ; Yemini et al, 2013 ), thereby phenocopying the unc-42 defects that we have described here ( Figure 2 ). Among these, flp-18 and npr-11 are expressed in command interneurons that are responsible for backward locomotion, and we found their expression to be unc-42 dependent in these neurons ( Figure 6C, K ).…”

A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior

“…Restricted expression in cholinergic motor neurons (VNC) 71 Punc-47 All GABAergic neurons 66 Pmyo-3 Muscles Podr-2 (16) SMD, RME 34 Plgc-55 SMD, IL1, AVB, RMD, neck muscles 33 Pgcy-28.d AIA 72 Plim-4(s) (lim-4 promoter fragment from -3328 to -2174 upstream of start) RIV 33 Pnpr-9 AIB 73 Podr-2 (18) RIG, SMB 34 Posm-6 ADE, amphid neurons, AQR, CEM, CEP, HOA, HOB, IL1, IL2, OLL, OLQ, PDE, phasmid neurons. 74…”

FLP-18 Functions through the G-Protein-Coupled Receptors NPR-1 and NPR-4 to Modulate Reversal Length inCaenorhabditis elegans

“…Although a number of studies have highlighted the neurons, molecules, and circuits that are required for the reversal behavior in C. elegans ( Chalfie et al, 1985 ; Kaplan and Horvitz, 1993 ; Hart et al, 1995 ; Maricq et al, 1995 ; Y. Zheng et al, 1999 ; Brockie et al, 2001 ; Zhao et al, 2003 ; Alkema et al, 2005 ; Gray et al, 2005 ; Cohen et al, 2009 ; Piggott et al, 2011 ; Campbell et al, 2016 ), most of these studies were focused on the reversal frequency. The role of neurons in regulating reversal length has to date been elaborated in a single previous study involving laser ablation of neurons ( Gray et al, 2005 ).…”