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Authors & Affiliations
Kaushik More, Cristian González-Cabrera, Andres Jaramillo Flautero, Aleksandra Gritskova, Matthew Betts, Matthias Prigge
Abstract
The Locus coeruleus (LC), the main noradrenaline-producing nucleus in the brain, is affected in a wide range of neurological conditions such as Parkinson's disease and Alzheimer's disease. Notably, the locus coeruleus-noradrenergic (LC-NA) system can be a therapeutic target through Vagus Nerve Stimulation. Transcutaneous auricular Vagus Nerve Stimulation (taVNS), an alternative technique that stimulates the auricular branch of the vagus nerve, is being studied as it’s less invasive, yet the nuanced neurocircuitry linking this branch of the vagus and LC remains unelucidated, as does the optimal stimulation parameters for LC-NA system activation. We conducted taVNS experiments in anesthetized mice using techniques like immunohistochemistry, viral tracing, and electrophysiology to engage the LC-NA system and study stimulation parameters that can maximize activation in the LC.We measured the cFOS in the LC and peri-LC region in two groups of animals, that were either stimulated with low current or with high current amplitude in experimental vs sham conditions. An increased cFOS signal was observed in the LC in the group with a higher current regime. Next, we used the juxtacellular recording and labeling technique to record from single neurons in the LC during taVNS while observing the firing pattern of the neuron for a higher temporal and spatial resolution than the cFOS readout. We observed increased firing activity in the neuron during the stimulation bouts and an increased effectiveness of stimulation after several repeated bouts. Furthermore, using pupillometry, we detected significant pupillary responses to taVNS, providing additional evidence of LC activation.