Modular Neural Circuits Underlying Learned Pathogen Avoidance Behavior in C. elegans

Alapfogalmak

Distinct sets of neurons drive the behavioral transitions from attraction to avoidance of pathogenic bacteria in C. elegans, revealing the modular structure of this complex adaptive response to infection.

Kivonat

The study investigates the neural circuits underlying the learned pathogen avoidance behavior in the nematode C. elegans. The key findings are:

Exposure to pathogenic bacteria (P. aeruginosa) causes a behavioral transition in C. elegans, from initial attraction to eventual avoidance of the pathogen. This transition involves two distinct behavioral modules - increased exit from the bacterial lawn and reduced re-entry into the lawn.

Using a compressed sensing-based optogenetic screen, the authors identified specific neuron types that regulate these two behavioral modules. Inhibition of neurons like AIY, SIA, and AVK during early pathogen exposure led to long-term changes in lawn exit and re-entry behaviors.

Calcium imaging of the identified neurons (AIY, AVK, SIA) revealed that pathogen exposure causes a sustained reduction in their neural activity, which appears to encode the memory of pathogen exposure.

Selective optogenetic activation of AIY and SIA/SIB neurons was able to reverse the pathogen-induced reduction in lawn re-entry, demonstrating the modularity of the neural circuits controlling these behavioral transitions.

The authors propose that the modular structure of the neural circuits underlying learned pathogen avoidance allows the worm to flexibly integrate sensory cues and generate an adaptive behavioral response to infection.

Statisztikák

Worms that had been exposed to pathogenic P. aeruginosa for 12 hours showed a 10-fold increase in the latency to re-enter the bacterial lawn compared to naive worms.
The rate constant for worms exiting the P. aeruginosa lawn increased from 0 to 1 exit event per worm-hour after 10 hours of exposure.
Inhibition of AIY neurons in naive worms increased the latency of re-entry onto P. aeruginosa lawns, but did not affect entry onto non-pathogenic E. coli lawns.
Inhibition of SIA/SIB neurons in naive worms also increased the latency of re-entry onto P. aeruginosa lawns.

Idézetek

"After several hours of exposure, animals associate infection with PA14 specific cues and change their behavior to avoid these bacteria."
"We find that key neuron types govern pathogen lawn specific stalling but allow the animal to enter nonpathogenic E. coli lawns."
"Our study shows that learned pathogen avoidance requires coordinated transitions in discrete neural circuits and reveals the modular structure of this complex adaptive behavioral response to infection."

Főbb Kivonatok

Compressed sensing based approach identifies modular neural circuitry driving learned pathogen avoidance

by Hallacy,T., ... : www.biorxiv.org 04-13-2024

https://www.biorxiv.org/content/10.1101/2024.04.10.588911v1

Mélyebb kérdések

How do the sensory inputs from the pathogenic bacteria integrate with the neural circuits identified in this study to drive the behavioral transitions?

In this study, the sensory inputs from pathogenic bacteria likely integrate with the identified neural circuits to drive the behavioral transitions through a complex interplay between sensory processing and neural activity modulation. The sensory cues from the pathogenic bacteria, such as chemosensory and mechanosensory inputs, are detected by specific sensory neurons like URX and CEP, which then transmit this information to the key interneurons identified in the study, such as AIY, SIA, and AVK. These interneurons act as integrators of the sensory information, processing and encoding the experience of pathogen exposure.
The modulation of neural activity in AIY, SIA, and AVK following pathogen exposure suggests that these neurons play a crucial role in encoding the memory of pathogen exposure and influencing subsequent behavior. The reduction in neural activity in these neurons after exposure to pathogenic bacteria indicates that they act as internal cues, signaling the history of exposure and driving the behavioral transitions. The distinct roles of these neurons in regulating lawn re-entry behavior highlight their specific contributions to the overall learned pathogen avoidance response.
Overall, the integration of sensory inputs from pathogenic bacteria with the identified neural circuits involves a sophisticated process of sensory detection, information processing, and neural activity modulation, ultimately leading to the behavioral transitions observed in learned pathogen avoidance.

How do the molecular mechanisms, such as neuropeptide signaling, mediate the long-term changes in neural dynamics and behavior following pathogen exposure?

Neuropeptide signaling, specifically involving molecules like PDF-2, plays a crucial role in mediating the long-term changes in neural dynamics and behavior following pathogen exposure. In the study, the expression of PDF-2 in AIY neurons suggests its involvement in modulating the neural activity and behavior associated with learned pathogen avoidance. PDF-2, along with its receptor PDFR-1, forms a potential feedback loop within AIY, contributing to the bistability of neural activity patterns and influencing long-term changes in behavior.
The reduction in neural activity in AIY, SIA, and AVK following pathogen exposure may be regulated by neuropeptide signaling pathways, such as PDF-2 signaling through the Rictor/TORC2 pathway. This signaling cascade could provide a mechanism for encoding the experience of pathogen exposure and maintaining the altered neural dynamics over time. By modulating the activity of key neurons involved in learned pathogen avoidance, neuropeptide signaling contributes to the consolidation and expression of the memory of pathogen exposure, leading to sustained changes in behavior.
Overall, neuropeptide signaling, particularly through molecules like PDF-2, serves as a molecular mechanism that mediates the long-term changes in neural dynamics and behavior following pathogen exposure, providing a link between sensory experience, neural activity modulation, and adaptive behavioral responses.

Could the modular structure of the neural circuits underlying learned pathogen avoidance be a general principle for how the nervous system encodes and responds to complex environmental stimuli?

The modular structure of the neural circuits underlying learned pathogen avoidance identified in this study could indeed represent a general principle for how the nervous system encodes and responds to complex environmental stimuli. The distinct sets of neurons governing specific behavioral transitions, such as exit from and re-entry onto pathogenic bacteria lawns, demonstrate a high degree of modularity in the control of adaptive behaviors. This modular organization allows for the independent regulation of different aspects of the behavioral response to pathogen exposure, ensuring precise and coordinated transitions in behavior.
The identification of key neurons responsible for specific subbehaviors, such as AIY and SIA for pathogen lawn re-entry, highlights the importance of discrete neural circuits in orchestrating complex behavioral responses. This modular structure enables the nervous system to efficiently process and integrate sensory information, encode experiences, and generate appropriate behavioral outputs in response to environmental stimuli.
Therefore, the modular organization of neural circuits, as observed in learned pathogen avoidance, likely represents a fundamental principle by which the nervous system encodes and responds to a wide range of complex environmental stimuli. This modular architecture allows for flexibility, adaptability, and specificity in behavioral responses, ensuring the organism's survival and fitness in dynamic and challenging environments.