The ability of animals to process dynamic sensory information facilitates foraging in an ever-changing environment. However, molecular and neural mechanisms underlying such ability remain elusive. ...The ClC anion channels/transporters play a pivotal role in cellular ion homeostasis across all phyla. Here, we find a ClC chloride channel is involved in salt concentration chemotaxis of
. Genetic screening identified two altered-function mutations of
that disrupt experience-dependent salt chemotaxis. Using genetically encoded fluorescent sensors, we demonstrate that CLH-1 contributes to regulation of intracellular anion and calcium dynamics of salt-sensing neuron, ASER. The mutant CLH-1 reduced responsiveness of ASER to salt stimuli in terms of both temporal resolution and intensity, which disrupted navigation strategies for approaching preferred salt concentrations. Furthermore, other ClC genes appeared to act redundantly in salt chemotaxis. These findings provide insights into the regulatory mechanism of neuronal responsivity by ClCs that contribute to modulation of navigation behavior.
Addiction has become a profound societal problem worldwide, and few effective treatments are available. The nematode
(
) is an excellent invertebrate model to study neurobiological disease states.
...reportedly developed a preference for cues that had previously been paired with addictive drugs, similar to place conditioning findings in rodents. Moreover, several recent studies discovered and reported the existence of an opioid-like system in
. Still unclear, however, is whether
exhibits addictive-like behaviors for opioids, such as morphine. In the present study, we found that
exhibited dose-dependent preference for morphine using the conditioned chemosensory-cue preference (CCP) test. This preference was blocked by co-treatment with the opioid receptor antagonist naloxone.
also exhibited aversion to naloxone-precipitated withdrawal from chronic morphine exposure. The expression of morphine-induced CCP and morphine withdrawal were abolished in worms that lacked the opioid-like receptor NPR-17. Dopamine-deficient mutant (
) worms also did not exhibit morphine-induced CCP. These results indicate that the addictive function of the opioid system exists in
, which may serve as a useful model of opioid addiction.
In the field of neuroscience, neural modules and circuits that control biological functions have been found throughout entire neural networks. Correlations in neural activity can be used to identify ...such neural modules. Recent technological advances enable us to measure whole-brain neural activity with single-cell resolution in several species including Formula: see text. Because current neural activity data in C. elegans contain many missing data points, it is necessary to merge results from as many animals as possible to obtain more reliable functional modules.
In this work, we developed a new time-series clustering method, WormTensor, to identify functional modules using whole-brain activity data from C. elegans. WormTensor uses a distance measure, modified shape-based distance to account for the lags and the mutual inhibition of cell-cell interactions and applies the tensor decomposition algorithm multi-view clustering based on matrix integration using the higher orthogonal iteration of tensors (HOOI) algorithm (MC-MI-HOOI), which can estimate both the weight to account for the reliability of data from each animal and the clusters that are common across animals.
We applied the method to 24 individual C. elegans and successfully found some known functional modules. Compared with a widely used consensus clustering method to aggregate multiple clustering results, WormTensor showed higher silhouette coefficients. Our simulation also showed that WormTensor is robust to contamination from noisy data. WormTensor is freely available as an R/CRAN package https://cran.r-project.org/web/packages/WormTensor .
Optimization of the types and timing of avoidance behaviors depending on the intensity of a noxious stimulus is essential for survival; however, processing in the central nervous system and its ...developmental basis are largely unknown. Here, we report that Caenorhabditis elegans preferentially selects one of three different types of avoidance behaviors depending on the strength of the noxious stimulus. We screened 210 neuronal transcription factors using a combination of optogenetics and RNA interference methods and identified 19 candidates required for avoidance behaviors. One candidate, gene lin-32 (abnormal cell LINeage 32), which encodes an atonal homolog, is required for the neural fate determination of AIB interneurons and functions by regulating the expression of electrical and chemical synapse genes, namely, inx-1 (innexin 1) and AMPA-type ionotropic glutamate receptor glr-1. When examined by Ca imaging, AIB showed an OFF calcium increase to the noxious stimulus. The OFF calcium increase was provoked only by strong stimulation, suggesting a role for optimization of the avoidance behavior. However, lin-32 mutants showed an impaired AIB OFF calcium increase, concomitant with a reduced occurrence of the dynamic avoidance behavior called the "omega turn". The AIB neural responses may be transferred to downstream inter/motor neurons projecting to the neck muscles via electrical synapses comprising inx-1. Finally, we found a correlation between powerful contractions of the neck muscles and omega turns. Thus, the central regulation of the magnitude and timing of activation of the AIB interneurons optimizes the probability of omega turn depending on the stimulus context.
Memorizing the intensity of sensory stimuli enables animals to successfully deal with changing environmental conditions and contributes to cognitive functions such as auditory and visual working ...memory. However, how nervous systems process past and current stimulus intensity is largely unknown at the molecular level. Here, we employ in vivo diacylglycerol (DAG) imaging in the ASER taste neuron of Caenorhabditis elegans and demonstrate that associative learning between ambient salt concentrations and food can be explained by changes in presynaptic DAG. The abundance of DAG is regulated in response to external salt concentration changes via sensory transduction in ASER and can encode differences between past and current salt concentrations. The DAG dynamics are modulated downstream of the synaptic insulin/phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which regulates the behavioral plasticity induced by starvation. These results provide insights into how a single neuron stores past input intensity and generates appropriate behavioral responses.
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•Presynaptic DAG is monitored in a taste neuron of C. elegans•Salt concentration shifts cause presynaptic DAG changes in fed worms•DAG is modulated downstream of the synaptic insulin/PI3K/Akt pathway•Presynaptic DAG dynamics are predictive of taste learning behavior
Animals adapt to environmental changes by memorizing the intensity of sensory stimuli. By employing diacylglycerol imaging and behavioral analyses, Ohno et al. show the in vivo dynamics of neuronal diacylglycerol and present insights into how a single neuron processes past and current stimulus intensity.
It is poorly understood how sensory systems memorize the intensity of sensory stimulus, compare it with a newly sensed stimulus, and regulate the orientation behaviour based on the memory. Here we ...report that Caenorhabditis elegans memorizes the environmental salt concentration during cultivation and exhibits a strong behavioural preference for this concentration. The right-sided amphid gustatory neuron known as ASER, senses decreases in salt concentration, and this information is transmitted to the postsynaptic AIB interneurons only in the salt concentration range lower than the cultivation concentration. In this range, animals migrate towards higher concentration by promoting turning behaviour upon decreases in salt concentration. These observations provide a mechanism for adjusting the orientation behaviour based on the memory of sensory stimulus using a simple neural circuit.
The nematode Caenorhabditis elegans memorizes various external chemicals, such as ions and odorants, during feeding. Here we find that C. elegans is attracted to the monosaccharides glucose and ...fructose after exposure to these monosaccharides in the presence of food; however, it avoids them without conditioning. The attraction to glucose requires a gustatory neuron called ASEL. ASEL activity increases when glucose concentration decreases. Optogenetic ASEL stimulation promotes forward movements; however, after glucose conditioning, it promotes turning, suggesting that after glucose conditioning, the behavioral output of ASEL activation switches toward glucose. We previously reported that chemotaxis toward sodium ion (Na.sup.+ ), which is sensed by ASEL, increases after Na.sup.+ conditioning in the presence of food. Interestingly, glucose conditioning decreases Na.sup.+ chemotaxis, and conversely, Na.sup.+ conditioning decreases glucose chemotaxis, suggesting the reciprocal inhibition of learned chemotaxis to distinct chemicals. The activation of PKC-1, an nPKC epsilon/eta ortholog, in ASEL promotes glucose chemotaxis and decreases Na.sup.+ chemotaxis after glucose conditioning. Furthermore, genetic screening identified ENSA-1, an ortholog of the protein phosphatase inhibitor ARPP-16/19, which functions in parallel with PKC-1 in glucose-induced chemotactic learning toward distinct chemicals. These findings suggest that kinase-phosphatase signaling regulates the balance between learned behaviors based on glucose conditioning in ASEL, which might contribute to migration toward chemical compositions where the animals were previously fed.
The recent advancements in large-scale activity imaging of neuronal ensembles offer valuable opportunities to comprehend the process involved in generating brain activity patterns and understanding ...how information is transmitted between neurons or neuronal ensembles. However, existing methodologies for extracting the underlying properties that generate overall dynamics are still limited. In this study, we applied previously unexplored methodologies to analyze time-lapse 3D imaging (4D imaging) data of head neurons of the nematode Caenorhabditis elegans. By combining time-delay embedding with the independent component analysis, we successfully decomposed whole-brain activities into a small number of component dynamics. Through the integration of results from multiple samples, we extracted common dynamics from neuronal activities that exhibit apparent divergence across different animals. Notably, while several components show common cooperativity across samples, some component pairs exhibited distinct relationships between individual samples. We further developed time series prediction models of synaptic communications. By combining dimension reduction using the general framework, gradient kernel dimension reduction, and probabilistic modeling, the overall relationships of neural activities were incorporated. By this approach, the stochastic but coordinated dynamics were reproduced in the simulated whole-brain neural network. We found that noise in the nervous system is crucial for generating realistic whole-brain dynamics. Furthermore, by evaluating synaptic interaction properties in the models, strong interactions within the core neural circuit, variable sensory transmission and importance of gap junctions were inferred. Virtual optogenetics can be also performed using the model. These analyses provide a solid foundation for understanding information flow in real neural networks.
Brains regulate behavioral responses with distinct timings. Here we investigate the cellular and molecular mechanisms underlying the timing of decision-making during olfactory navigation in
. We find ...that, based on subtle changes in odor concentrations, the animals appear to choose the appropriate migratory direction from multiple trials as a form of behavioral decision-making. Through optophysiological, mathematical and genetic analyses of neural activity under virtual odor gradients, we further find that odor concentration information is temporally integrated for a decision by a gradual increase in intracellular calcium concentration (Ca
), which occurs via L-type voltage-gated calcium channels in a pair of olfactory neurons. In contrast, for a reflex-like behavioral response, Ca
rapidly increases via multiple types of calcium channels in a pair of nociceptive neurons. Thus, the timing of neuronal responses is determined by cell type-dependent involvement of calcium channels, which may serve as a cellular basis for decision-making.
Peptide signaling controls many processes involving coordinated actions of multiple organs, such as hormone-mediated appetite regulation. However, the extent to which the mode of action of peptide ...signaling is conserved in different animals is largely unknown, because many peptides and receptors remain orphan and many undiscovered peptides still exist. Here, we identify two novel
neuropeptides, LURY-1-1 and LURY-1-2, as endogenous ligands for the neuropeptide receptor-22 (NPR-22). Both peptides derive from the same precursor that is orthologous to invertebrate luqin/arginine-tyrosine-NH
(RYamide) proneuropeptides. LURY-1 peptides are secreted from two classes of pharyngeal neurons and control food-related processes: feeding, lifespan, egg-laying, and locomotory behavior. We propose that LURY-1 peptides transmit food signals to NPR-22 expressed in feeding pacemaker neurons and a serotonergic neuron. Our results identified a critical role for luqin-like RYamides in feeding-related processes and suggested that peptide-mediated negative feedback is important for satiety regulation in
.
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