Szilagyi, G. S. | Search bioRxiv

bioRxiv2025

Signed motif analysis of the Caenorhabditis elegans neuronal network reveals positive feedforward and negative feedback loops

BackgroundNervous systems are complex biological networks with largely unknown structural and functional characteristics. Motif analysis is a robust tool that can reveal the unique aspects of connectivity in a complex network. An ideal candidate for motif analysis is the connectome of the nematode Caenorhabditis elegans, which is the first fully reconstructed nervous system. ResultsWe performed, for the first time, edge-polarity based signed motif analysis on the C. elegans connectome using recent data on the connection signs of this network and a novel structure-preserving randomization method. We identified 56 significantly over- and 1 underrepresented three-node signed motifs and revealed that certain motifs (e.g., positive feedforward, negative feedback, disinhibitory feedback, and incoherent feedforward loops) are overabundant in the C. elegans connectome. We further distinguished nodes by their corresponding neuron modalities (e.g., sensory vs. motor neurons), and found that each significant feedforward and feedback loop has a characteristic neuronal layout. ConclusionsOur findings demonstrate the importance and potential of signed motif analysis in understanding biological networks. The motif enumeration tool and definition system we developed can be used to analyze signed motifs in other complex networks.

systems biology↗

bioRxiv2020

Synaptic polarity and sign-balance prediction using gene expression data in the Caenorhabditis elegans chemical synapse neuronal connectome network

Graph theoretical analyses of nervous systems usually omit the aspect of connection polarity, due to data insufficiency. The chemical synapse network of Caenorhabditis elegans is a well-reconstructed directed network, but the signs of its connections are yet to be elucidated. Here, we present the gene expression-based sign prediction of the C. elegans connectome, incorporating presynaptic neurotransmitter and postsynaptic receptor gene expression data (3,638 connections and 20,589 synapses total). We made successful predictions for more than two-thirds of all chemical synapses and determined a ratio of excitatory-inhibitory (E:I) interneuronal ionotropic chemical connections close to 4:1 which was found similar to that observed in many real-world networks. Our open source tool (http://EleganSign.linkgroup.hu) is simple but efficient in predicting polarities by integrating neuronal connectome and gene expression data. Author SummaryThe fundamental way neurons communicate is by activating or inhibiting each other via synapses. The balance between the two is crucial for the optimal functioning of a nervous system. However, whole-brain synaptic polarity information is unavailable for any species and experimental validation is challenging. The roundworm Caenorhabditis elegans possesses a fully mapped connectome with a comprehensive gene expression profile of its 302 neurons. Based on the consideration that the polarity of a synapse must be determined by the neurotransmitter(s) expressed in the presynaptic neuron and the receptors expressed in the postsynaptic neuron, we conceptualized and created a tool that predicts synaptic polarities based on connectivity and gene expression information. We were able to show for the first time that the ratio of excitatory and inhibitory synapses in C. elegans is around 4 to 1 which is in line with the balance observed in many natural systems. Our method opens a way to include spatial and temporal dynamics of synaptic polarity that would add a new dimension of plasticity in the excitatory:inhibitory balance. Our tool is freely available to be used on any network accompanied by any expression atlas.

neuroscience↗