Abstract

Intracortical microstimulation (ICMS) enables applications ranging from neuroprosthetics to causal circuit manipulations. However, the resolution, efficacy, and chronic stability of neuromodulation are often compromised by adverse tissue responses to the indwelling electrodes. Here we engineer ultraflexible stim-nanoelectronic threads (StimNETs) and demonstrate low activation threshold, high resolution, and chronically stableICMS in awake, behaving mouse models. Invivo two-photon imaging reveals that StimNETs remain seamlessly integrated with the nervous tissue throughout chronic stimulation periods and elicit stable, focal neuronal activation at low currents of 2μA. Importantly, StimNETs evoke longitudinally stable behavioral responses for over 8months at a markedly low charge injection of 0.25 nC/phase. Quantified histological analyses show that chronic ICMS by StimNETs induces no neuronal degeneration or glial scarring. These results suggest that tissue-integrated electrodes provide a path for robust, long-lasting, spatially selective neuromodulation at low currents, which lessens risk of tissue damage or exacerbation of off-target side effects.

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