ArticleiScience2026
Multimodal atlas of single neuron metabolic electrophysiological coupling uncovers circadian rewiring.
Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
Neuronal metabolism fundamentally modulates synaptic activity, yet how single-cell metabolic architecture aligns with electrophysiological diversity remains elusive. By integrating patch-clamp electrophysiology with single-neuron mass spectrometry (SNMS), we resolve metabolomic heterogeneity across suprachiasmatic nucleus (SCN) neurons, revealing six metabolic states with distinct synaptic dynamics, from lipid-enriched SCN1 exhibiting high-frequency presynaptic activity to quiescent SCN6. Pathway analysis linked metabolic state-specific signatures to sulfur metabolism, glutathione regulation, and citrate cycle dynamics. Machine learning and correlation networks mapped metabolites to functional parameters: histidine, carnitine, and creatinine regulated neuronal activity, validated by intracellular metabolite delivery experiments. Strikingly, light-dark cycles dynamically reconfigured most of the metabolite-postsynaptic current correlations, including light-induced taurine coupling to synaptic transmission. This multimodal platform establishes cellular metabolism as a tunable factor associated with neuronal heterogeneity and circadian plasticity, suggesting potential therapeutic avenues for circadian disorders.
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