Rajeev, P. | Search bioRxiv

bioRxiv2025

Nanoscale Lattice Organization of Molecular Condensates Drives Compositional Degeneracy in Synaptic Plasticity

Synaptic plasticity is essential for neuronal communication, involving coordinated structural, molecular and functional changes that are shaped by the nanoscale alterations of the active zone and postsynaptic density. Emerging evidence suggests that synapses function as complex information processing machines, where unique molecular assemblies shape transmission properties. Central to this is the organization of voltage-gated calcium channels (VGCCs) and Bassoon within active zones. Utilizing advanced techniques like liquid-liquid phase separation, super-resolution microscopy, and data-driven models of synaptic transmission, we reveal how nanoscale "compositional degeneracy" in Bassoon and VGCCs enables synapses to achieve functional adaptability through multiple molecular configurations. By modulation of local uncertainty and implementing probabilistic inference, synapses fine-tune transmission efficiency by regulating dynamic entropy and free energy. These principles are especially evident during homeostatic scaling, where synaptic scaling mechanisms differ with neuronal maturity. This study highlights how distinct thermodynamic states in VGCC and Bassoon organization optimize information transfer at different plasticity stages. Our findings propose a refined framework for understanding synaptic transmission as an adaptable, entropy-modulated process, balancing resilience and efficiency.

neuroscience↗

bioRxiv2017

Tracking electron uptake from a cathode into Shewanella cells: implications for generating maintenance energy from solid substrates.

While typically investigated as a microorganism capable of extracellular electron transfer to minerals or anodes, Shewanella oneidensis MR-1 can also facilitate electron flow from a cathode to terminal electron acceptors such as fumarate or oxygen, thereby providing a model systems for a process that has significant environmental and technological implications. This work demonstrates that cathodic electrons enter the electron transport chain of S. oneidensis when oxygen is used as the terminal electron acceptor. The effect of electron transport chain inhibitors suggested that a proton gradient is generated during cathode-oxidation, consistent with the higher cellular ATP levels measured in cathode-respiring cells relative to controls. Cathode oxidation also correlated with an increase in the cellular redox (NADH/FMNH2) pool using a bioluminescent assay. Using a proton uncoupler, generation of NADH/FMNH2 under cathodic conditions was linked to reverse electron flow mediated by the proton pumping NADH oxidase Complex I. A decrease in cathodic electron uptake was observed in various mutant strains including those lacking the extracellular electron transfer components necessary for anodic current generation. While no cell growth was observed under these conditions, here we show that cathode oxidation is linked to cellular energy conservation, resulting in a quantifiable reduction in cellular decay rate. This work highlights a potential mechanism for cell survival and/or persistence in environments where growth and division are severely limited.

microbiology↗