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

2020 ◽  
Author(s):  
Shankar Ramachandran ◽  
Navonil Banerjee ◽  
Raja Bhattacharya ◽  
Denis Touroutine ◽  
Christopher M. Lambert ◽  
...  

SUMMARYNeuromodulators promote adaptive behaviors in response to either environmental or internal physiological changes. These responses are often complex and may involve concerted activity changes across circuits that are not physically connected. It is not well understood how neuromodulatory systems act across circuits to elicit complex behavioral responses. Here we show that the C. elegans NLP-12 neuropeptide system shapes responses to food availability by selectively modulating the activity of head and body wall motor neurons. NLP-12 modulation of the head and body wall motor circuits is generated through conditional involvement of alternate GPCR targets. The CKR-1 GPCR is highly expressed in the head motor circuit, and functions to enhance head bending and increase trajectory reorientations during local food searching, primarily through stimulatory actions on SMD head motor neurons. In contrast, NLP-12 activation of CKR-1 and CKR-2 GPCRs regulates body bending under basal conditions, primarily through actions on body wall motor neurons. Thus, locomotor responses to changing environmental conditions emerge from conditional NLP-12 stimulation of head or body wall motor neuron targets.

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Shankar Ramachandran ◽  
Navonil Banerjee ◽  
Raja Bhattacharya ◽  
Michele L Lemons ◽  
Jeremy Florman ◽  
...  

Neuromodulators promote adaptive behaviors that are often complex and involve concerted activity changes across circuits that are often not physically connected. It is not well understood how neuromodulatory systems accomplish these tasks. Here we show that the C. elegans NLP-12 neuropeptide system shapes responses to food availability by modulating the activity of head and body wall motor neurons through alternate G-protein coupled receptor (GPCR) targets, CKR-1 and CKR-2. We show ckr-2 deletion reduces body bend depth during movement under basal conditions. We demonstrate CKR-1 is a functional NLP-12 receptor and define its expression in the nervous system. In contrast to basal locomotion, biased CKR-1 GPCR stimulation of head motor neurons promotes turning during local searching. Deletion of ckr-1 reduces head neuron activity and diminishes turning while specific ckr-1 overexpression or head neuron activation promote turning. Thus, our studies suggest locomotor responses to changing food availability are regulated through conditional NLP-12 stimulation of head or body wall motor circuits.


2021 ◽  
Vol 15 ◽  
Author(s):  
Sydney Popsuj ◽  
Alberto Stolfi

Conserved transcription factors termed “terminal selectors” regulate neuronal sub-type specification and differentiation through combinatorial transcriptional regulation of terminal differentiation genes. The unique combinations of terminal differentiation gene products in turn contribute to the functional identities of each neuron. One well-characterized terminal selector is COE (Collier/Olf/Ebf), which has been shown to activate cholinergic gene batteries in C. elegans motor neurons. However, its functions in other metazoans, particularly chordates, is less clear. Here we show that the sole COE ortholog in the non-vertebrate chordate Ciona robusta, Ebf, controls the expression of the cholinergic locus VAChT/ChAT in a single dorsal interneuron of the larval Motor Ganglion, which is presumed to be homologous to the vertebrate spinal cord. We propose that, while the function of Ebf as a regulator of cholinergic neuron identity conserved across bilaterians, its exact role may have diverged in different cholinergic neuron subtypes (e.g., interneurons vs. motor neurons) in chordate-specific motor circuits.


2021 ◽  
Author(s):  
Yangning Lu ◽  
Tosif Ahamed ◽  
Ben Mulcahy ◽  
Daniel Witvliet ◽  
Sihui Asuka Guan ◽  
...  

Bilaterians generate motor patterns with symmetries that correspond to their body plans. This is thought to arise from wiring symmetries in their motor circuitries. We show that juvenile C. elegans larva has an asymmetrically wired motor circuit, but they still generate bending pattern with dorsal-ventral symmetry. In this juvenile circuit, wiring between excitatory and inhibitory motor neurons drives and coordinates contraction of dorsal muscles with relaxation of ventral muscles, producing dorsal bends. Ventral bending is not driven by its own circuitry. Instead, ventral muscles are excited uniformly by premotor interneurons through extrasynaptic signaling, and ventral bends occur in entrainment to the activity of motor neurons for dorsal bends. During maturation, the juvenile motor circuit is replaced by two homologous motor circuits that separately generate dorsal and ventral bending. Our modeling reveals that the juvenile circuit configuration provides an adequate solution for an immature motor circuit to drive functional gait long before the animal matures.


2020 ◽  
Author(s):  
Richard J. Kopchock ◽  
Bhavya Ravi ◽  
Addys Bode ◽  
Kevin M. Collins

AbstractSuccessful execution of behavior requires the coordinated activity and communication between multiple cell types. Studies using the relatively simple neural circuits of invertebrates have helped to uncover how conserved molecular and cellular signaling events shape animal behavior. To understand the mechanisms underlying neural circuit activity and behavior, we have been studying a simple circuit that drives egg-laying behavior in the nematode worm C. elegans. Here we show that the female-specific, Ventral C (VC) motoneurons are required for vulval muscle contractility and egg laying in response to serotonin. Ca2+ imaging experiments show the VCs are active during times of vulval muscle contraction and vulval opening, and optogenetic stimulation of the VCs promotes vulval muscle Ca2+ activity. However, while silencing of the VCs does not grossly affect steady-state egg-laying behavior, VC silencing does block egg laying in response to serotonin and increases the failure rate of egg-laying attempts. Signaling from the VCs facilitates full vulval muscle contraction and opening of the vulva for efficient egg laying. We also find the VCs are mechanically activated in response to vulval opening. Optogenetic stimulation of the vulval muscles is sufficient to drive VC Ca2+ activity and requires muscle contractility, showing the presynaptic VCs and the postsynaptic vulval muscles can mutually excite each other. Together, our results demonstrate that the VC neurons facilitate efficient execution of egg-laying behavior by coordinating postsynaptic muscle contractility in response to serotonin and mechanosensory feedback.


2019 ◽  
Author(s):  
Negin Azimi Hashemi ◽  
Amelie C. F. Bergs ◽  
Rebecca Scheiwe ◽  
Wagner Steuer Costa ◽  
Jana F. Liewald ◽  
...  

AbstractGenetically encoded voltage indicators (GEVIs) based on microbial rhodopsins utilize the voltage-sensitive fluorescence of the all-trans retinal (ATR) cofactor, while in electrochromic (eFRET) sensors, donor fluorescence drops when the rhodopsin acts as depolarization-sensitive acceptor. We systematically assessed Arch(D95N), Archon, and QuasAr, as well as the eFRET sensors MacQ-mCitrine and QuasAr-mOrange, in C. elegans. ATR-bearing rhodopsins reported on voltage changes in body wall muscles (BWMs) and the pharynx, the feeding organ, where Arch(D95N) showed ca. 125 % ΔF/F increase per 100 mV. The ATR fluorescence is very dim, however, using the retinal analog dimethylaminoretinal (DMAR), it was boosted 250-fold. eFRET sensors provided sensitivities of 45 % to 78 % ΔF/F per 100 mV, induced by BWM action potentials (APs). All sensors reported differences in muscle depolarization induced by a voltage-gated Ca2+-channel mutant. Optogenetically evoked de-or hyperpolarization of motor neurons increased or eliminated AP activity and caused a rise or drop in BWM sensor fluorescence. Last, we could analyze voltage dynamics across the entire pharynx, showing uniform depolarization but compartmentalized repolarization of anterior and posterior parts. Our work establishes all-optical, non-invasive electrophysiology in intact C. elegans.


2021 ◽  
Vol 413 (8) ◽  
pp. 2091-2102
Author(s):  
Michael Witting ◽  
Ulrike Schmidt ◽  
Hans-Joachim Knölker

AbstractLipid identification is one of the current bottlenecks in lipidomics and lipid profiling, especially for novel lipid classes, and requires multidimensional data for correct annotation. We used the combination of chromatographic and ion mobility separation together with data-independent acquisition (DIA) of tandem mass spectrometric data for the analysis of lipids in the biomedical model organism Caenorhabditis elegans. C. elegans reacts to harsh environmental conditions by interrupting its normal life cycle and entering an alternative developmental stage called dauer stage. Dauer larvae show distinct changes in metabolism and morphology to survive unfavorable environmental conditions and are able to survive for a long time without feeding. Only at this developmental stage, dauer larvae produce a specific class of glycolipids called maradolipids. We performed an analysis of maradolipids using ultrahigh performance liquid chromatography-ion mobility spectrometry-quadrupole-time of flight-mass spectrometry (UHPLC-IM-Q-ToFMS) using drift tube ion mobility to showcase how the integration of retention times, collisional cross sections, and DIA fragmentation data can be used for lipid identification. The obtained results show that combination of UHPLC and IM separation together with DIA represents a valuable tool for initial lipid identification. Using this analytical tool, a total of 45 marado- and lysomaradolipids have been putatively identified and 10 confirmed by authentic standards directly from C. elegans dauer larvae lipid extracts without the further need for further purification of glycolipids. Furthermore, we putatively identified two isomers of a lysomaradolipid not known so far. Graphical abstract


Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 211-224 ◽  
Author(s):  
Joseph H Chou ◽  
Cornelia I Bargmann ◽  
Piali Sengupta

Abstract Caenorhabditis elegans odr-2 mutants are defective in the ability to chemotax to odorants that are recognized by the two AWC olfactory neurons. Like many other olfactory mutants, they retain responses to high concentrations of AWC-sensed odors; we show here that these residual responses are caused by the ability of other olfactory neurons (the AWA neurons) to be recruited at high odor concentrations. odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signaling proteins and is the founding member of a C. elegans gene family with at least seven other members. Alternative splicing of odr-2 yields three predicted proteins that differ only at the extreme amino terminus. The three isoforms have different promoters, and one isoform may have a unique role in olfaction. An epitope-tagged ODR-2 protein is expressed at high levels in sensory neurons, motor neurons, and interneurons and is enriched in axons. The AWC neurons are superficially normal in their development and structure in odr-2 mutants, but their function is impaired. Our results suggest that ODR-2 may regulate AWC signaling within the neuronal network required for chemotaxis.


1984 ◽  
Vol 52 (1) ◽  
pp. 54-73 ◽  
Author(s):  
D. F. Russell ◽  
D. K. Hartline

The properties of neurons in the stomatogastric ganglion (STG) participating in the pattern generator for the gastric mill rhythm were studied by intracellular current injection under several conditions: during ongoing gastric rhythms, in the nonrhythmic isolated STG, after stimulation of the nerve carrying central nervous system (CNS) inputs to the STG, or under Ba2+ or Sr2+. Slow regenerative depolarizations during ongoing rhythms were demonstrated in the anterior median, cardiopyloric, lateral cardiac, gastropyloric, and continuous inhibitor (AM, CP, LC, GP, and CI) neurons according to criteria such as voltage dependency, burst triggering, and termination by brief current pulses, etc. Experiments showed that regenerative-like behavior was not due to synaptic network interactions. The slow regenerative responses were abolished by isolating the stomatogastric ganglion but could be reestablished by stimulating the input nerve. This indicates that certain CNS inputs synaptically induce the regenerative property in specific gastric neurons. Slow regenerative depolarizations were not demonstrable in gastric mill (GM) motor neurons. Their burst oscillations and firing rate were instead proportional to injected current. CNS inputs evoked a prolonged depolarization in GM motor neurons, apparently by a nonregenerative mechanism. All the gastric cells showed prolonged regenerative potentials under 0.5-1.5 mM Ba2+. We conclude that the gastric neurons of the STG can be divided into three types according to their properties: those with a regenerative capability, a repetitively firing type, and a nonregenerative "proportional" type. The cells are strongly influenced by several types of CNS inputs, including "gastric command fibers."


Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1611-1622 ◽  
Author(s):  
Go Shioi ◽  
Michinari Shoji ◽  
Masashi Nakamura ◽  
Takeshi Ishihara ◽  
Isao Katsura ◽  
...  

Abstract Using a pan-neuronal GFP marker, a morphological screen was performed to detect Caenorhabditis elegans larval lethal mutants with severely disorganized major nerve cords. We recovered and characterized 21 mutants that displayed displacement or detachment of the ventral nerve cord from the body wall (Ven: ventral cord abnormal). Six mutations defined three novel genetic loci: ven-1, ven-2, and ven-3. Fifteen mutations proved to be alleles of previously identified muscle attachment/positioning genes, mup-4, mua-1, mua-5, and mua-6. All the mutants also displayed muscle attachment/positioning defects characteristic of mua/mup mutants. The pan-neuronal GFP marker also revealed that mutants of other mua/mup loci, such as mup-1, mup-2, and mua-2, exhibited the Ven defect. The hypodermis, the excretory canal, and the gonad were morphologically abnormal in some of the mutants. The pleiotropic nature of the defects indicates that ven and mua/mup genes are required generally for the maintenance of attachment of tissues to the body wall in C. elegans.


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