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Varanasi, V.

Publications and source records attributed to Varanasi, V..

2 recordsLinked to original sources

Heavy-tailed connections support robust neural communication

In the synaptic wiring between neurons, some rare connections are orders of magnitude stronger than most. This heavy-tailed connectivity is ubiquitous across different species, brain regions, and cell types, suggesting that it serves a general purpose for neural function. Here, we show, both analytically and in simulations, that heavy-tailed connections reduce communication errors in the presence of synaptic noise. In minimal models of individual neurons, noisy connections induce errors at a rate that depends only on a simple network statistic, which we refer to as robustness. For a fixed number of incoming synapses, neurons with broader distributions of connection strength are more robust and, therefore, admit fewer errors. Across several connectomes, we find that real neurons are consistently more robust than comparable null networks. In the whole brain of the fruit fly Drosophila, robustness increases with distance from the sensory periphery, such that central neurons are more robust than those involved in sensory processing. Together, these results indicate that heavy-tailed connections may arise universally to fortify the brain against noise in communication.

neuroscience↗

Benzothiazole Derivatives as Dual Modulators of PGE2 and GABAergic Signaling in Skeletal Muscle

Benzothiazoles are attractive scaffolds for small-molecule modulators of neuronal signaling. However, their impact on skeletal muscle and GABAergic pathways remains poorly understood. We synthesized a focused library of benzothiazole derivatives via oxidative electrophilic substitution and profiled their activity in C2C12 skeletal muscle cells, assessing cytotoxicity, proliferation, myogenic differentiation, and GABA-related signaling using cell-based assays, real-time PCR, and transcriptomics. Omics-guided analyses revealed that selected benzothiazole derivatives differentially modulate myogenic differentiation and prostaglandin E2, and simultaneously bidirectionally regulate GABAergic and glutamatergic signaling genes, including synaptic subunits and transporters. Notably, a lead derivative downregulated Gabrg2, a GABA-A receptor subunit implicated in epilepsy and other disorders of inhibitory synapses, highlighting a potential link between skeletal muscle signaling and neuropsychiatric disease. These findings position benzothiazole derivatives as candidate modulators of GABAergic signaling with translational potential for conditions involving dysfunctional inhibitory synapses.

pharmacology and toxicology↗