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1. Biophysical modeling of the whole-cell dynamics of C. elegans motor and interneurons families

   https://doi.org/10.1371/journal.pone.0298105  

   Nicoletti, Martina; Chiodo, Letizia; Loppini, Alessandro; Liu, Qiang; Folli, Viola; Ruocco, Giancarlo; Filippi, Simonetta (March 2024, PLOS ONE)

   Cymbalyuk, Gennady S (Ed.)

   The nematodeCaenorhabditis elegansis a widely used model organism for neuroscience. Although its nervous system has been fully reconstructed, the physiological bases of single-neuron functioning are still poorly explored. Recently, many efforts have been dedicated to measuring signals fromC.elegansneurons, revealing a rich repertoire of dynamics, including bistable responses, graded responses, and action potentials. Still, biophysical models able to reproduce such a broad range of electrical responses lack. Realistic electrophysiological descriptions started to be developed only recently, merging gene expression data with electrophysiological recordings, but with a large variety of cells yet to be modeled. In this work, we contribute to filling this gap by providing biophysically accurate models of six classes ofC.elegansneurons, the AIY, RIM, and AVA interneurons, and the VA, VB, and VD motor neurons. We test our models by comparing computational and experimental time series and simulate knockout neurons, to identify the biophysical mechanisms at the basis of inter and motor neuron functioning. Our models represent a step forward toward the modeling ofC.elegansneuronal networks and virtual experiments on the nematode nervous system. 

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2. Mitochondrial stress in GABAergic neurons non-cell autonomously regulates organismal health and aging

   https://doi.org/10.1101/2024.03.20.585932  

   Rathor, Laxmi; Curry, Shayla; Park, Youngyong; McElroy, Taylor; Robles, Briana; Sheng, Yi; Chen, Wei-Wen; Min, Kisuk; Xiao, Rui; Lee, Myon Hee; et al (March 2024, bioRxiv)

   Abstract Mitochondrial stress within the nervous system can trigger non-cell autonomous responses in peripheral tissues. However, the specific neurons involved and their impact on organismal aging and health have remained incompletely understood. Here, we demonstrate that mitochondrial stress in γ-aminobutyric acid-producing (GABAergic) neurons inCaenorhabditis elegans(C. elegans) is sufficient to significantly alter organismal lifespan, stress tolerance, and reproductive capabilities. This mitochondrial stress also leads to significant changes in mitochondrial mass, energy production, and levels of reactive oxygen species (ROS). DAF-16/FoxO activity is enhanced by GABAergic neuronal mitochondrial stress and mediates the induction of these non-cell-autonomous effects. Moreover, our findings indicate that GABA signaling operates within the same pathway as mitochondrial stress in GABAergic neurons, resulting in non-cell-autonomous alterations in organismal stress tolerance and longevity. In summary, these data suggest the crucial role of GABAergic neurons in detecting mitochondrial stress and orchestrating non-cell-autonomous changes throughout the organism. 

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3. Systematic generation of biophysically detailed models with generalization capability for non-spiking neurons

   https://doi.org/10.1371/journal.pone.0268380  

   Naudin, Loïs; Jiménez Laredo, Juan Luis; Liu, Qiang; Corson, Nathalie (May 2022, PLOS ONE)

   Guo, Daqing (Ed.)

   Unlike spiking neurons which compress continuous inputs into digital signals for transmitting information via action potentials, non-spiking neurons modulate analog signals through graded potential responses. Such neurons have been found in a large variety of nervous tissues in both vertebrate and invertebrate species, and have been proven to play a central role in neuronal information processing. If general and vast efforts have been made for many years to model spiking neurons using conductance-based models (CBMs), very few methods have been developed for non-spiking neurons. When a CBM is built to characterize the neuron behavior, it should be endowed with generalization capabilities ( i.e . the ability to predict acceptable neuronal responses to different novel stimuli not used during the model’s building). Yet, since CBMs contain a large number of parameters, they may typically suffer from a lack of such a capability. In this paper, we propose a new systematic approach based on multi-objective optimization which builds general non-spiking models with generalization capabilities. The proposed approach only requires macroscopic experimental data from which all the model parameters are simultaneously determined without compromise. Such an approach is applied on three non-spiking neurons of the nematode Caenorhabditis elegans ( C. elegans ), a well-known model organism in neuroscience that predominantly transmits information through non-spiking signals. These three neurons, arbitrarily labeled by convention as RIM, AIY and AFD, represent, to date, the three possible forms of non-spiking neuronal responses of C. elegans . 

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4. A neurotransmitter produced by gut bacteria modulates host sensory behavior.

   https://doi.org/DOI: 10.1038/s41586-020-2395-5  

   O'Donnell, Michael P; Fox, Bennett W; Chao, Pin-Hao; Schroeder, Frank C; Sengupta, Piali (June 2020, Nature)

   Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms1. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts2,3. However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans, the neuromodulator tyramine produced by commensal Providencia bacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine β-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis in Providencia, and show that these genes are necessary for the modulation of host behaviour. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism. 

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5. Computational Methods for Predicting and Understanding Food Judgment

   https://doi.org/10.1177/09567976211043426  

   Gandhi, Natasha; Zou, Wanling; Meyer, Caroline; Bhatia, Sudeep; Walasek, Lukasz (April 2022, Psychological Science)

   People make subjective judgments about the healthiness of different foods every day, and these judgments in turn influence their food choices and health outcomes. Despite the importance of such judgments, there are few quantitative theories about their psychological underpinnings. This article introduces a novel computational approach that can approximate people’s knowledge representations for thousands of common foods. We used these representations to predict how both lay decision-makers (the general population) and experts judge the healthiness of individual foods. We also applied our method to predict the impact of behavioral interventions, such as the provision of front-of-pack nutrient and calorie information. Across multiple studies with data from 846 adults, our models achieved very high accuracy rates ( r 2 = .65–.77) and significantly outperformed competing models based on factual nutritional content. These results illustrate how new computational methods applied to established psychological theory can be used to better predict, understand, and influence health behavior. 

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