Thermodynamic connectivity reveals functional specialization and multiplex organization of extrasynaptic signaling

TL;DR

This study uses a multiplex framework to analyze how synaptic and extrasynaptic signaling organize brain function in C. elegans, revealing four specialized communication regimes that support different neural functions.

Contribution

The paper introduces a unified multiplex approach linking anatomical wiring to functional communication, integrating synaptic and extrasynaptic connectomes using equilibrium principles.

Findings

Identified four distinct communication regimes with specific functional roles.

Revealed that synaptic and extrasynaptic signaling form complementary, specialized architectures.

Provided a general strategy for integrating structural and modulatory connectomes.

Abstract

Neural communication operates on both fast synaptic transmission and slower, diffusive extrasynaptic signaling, yet how these two modes jointly organize brain function remains unclear. Here, using the complete synaptic and neuropeptidergic connectomes of \emph{Caenorhabditis elegans}, we develop a unified multiplex framework linking anatomical wiring to functional communication. We infer structure-derived functional connectivity from the synaptic connectome using equilibrium principles from statistical physics, yielding a probabilistic map of information flow across all synaptic pathways, and compare this functional layer directly with the extrasynaptic connectome. This reveals a principled functional specialization across four communication regimes: (i) a topology-dependent layer that reinforces and stabilizes synaptic motor circuits, (ii) a topology-resilient modulatory layer supporting global regulation and behavioral state control, (iii) a purely extrasynaptic network sustaining survival and homeostasis, and (iv) a purely synaptic regime mediating rapid, low-latency sensorimotor processing. Together, these findings reveal that synaptic and extrasynaptic signaling form complementary architectures optimized for speed, modulation, robustness, and survival, and provide a general strategy for integrating structural and modulatory connectomes to understand how distinct communication modes cooperate to sustain coherent brain function.