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bioRxiv · 10.1101/2025.07.01.662561

High frequency electrical stimulation entrains fast spiking interneurons and bidirectionally modulates information processing

Fabris, P.·Lowet, E.·Kondabolu, K.·Wang, Y.·Zhou, Y.·Han, X.
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Abstract

BackgroundClinical intracranial electrical stimulation often deploys trains of high frequency pulses. While brief bursts of stimulation are known to heterogeneously modulate neuronal spiking, it is unclear how trains of high frequency pulses influence neural dynamics. ObjectiveAs fast spiking interneurons (FSIs) can support rapid firing, we seek to determine how high frequency stimulation modulates FSIs. MethodsWe characterized the real-time effect of one-second-long local stimulation at 40 versus 140 Hz on parvalbumin positive interneurons, known as FSIs, in motor and visual cortices in awake mice using near kilohertz voltage imaging, free of electrical stimulation artifact. ResultsStimulation at 140 Hz, like 40 Hz, heterogeneously modulates individual FSIs membrane voltage in both cortices, leading to complex temporal dynamics. FSIs in both cortices are robustly entrained by 40 Hz stimulation, even though 40 Hz led to prominent membrane hyperpolarization in visual cortex but not motor cortex. Intriguingly, visual cortical FSIs, but not motor cortical ones, were reliably entrained by 140 Hz stimulation. Finally, while stimulation consistently reduced the response amplitude of visual cortical FSIs to visual flickers, response temporal precision is bidirectionally modulated. ConclusionHigh frequency electrical stimulation mediates brain-region specific entrainment of FSIs, and bidirectionally modulates FSI temporal processing of synaptic inputs. Thus, high frequency stimulation can differentially engage inhibitory neurons in different brain regions to modulate network information processing. HighlightsO_LIEvoked membrane potential (Vm) responses are frequency and brain region specific C_LIO_LI140 Hz stimulation entrains the Vm of visual, but not motor, cortical FSIs C_LIO_LI140 Hz, but not 40 Hz, is effective at reducing Vm amplitude to visual flickers C_LIO_LIStimulation bidirectionally modulates Vm response timing to visual inputs C_LIO_LIVisual cortical FSIs are suppressed by 40 Hz stimulation, unlike other conditions C_LI

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Fabris, P., Lowet, E., Kondabolu, K., Wang, Y., Zhou, Y., Han, X.. 2025-07-04. High frequency electrical stimulation entrains fast spiking interneurons and bidirectionally modulates information processing. https://doi.org/10.1101/2025.07.01.662561

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