Deep brain stimulation creates informational lesion through membrane depolarization in mouse hippocampus

Eric Lowet (), Krishnakanth Kondabolu, Samuel Zhou, Rebecca A. Mount, Yangyang Wang, Cara R. Ravasio and Xue Han ()
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Eric Lowet: Boston University, Department of Biomedical Engineering
Krishnakanth Kondabolu: Boston University, Department of Biomedical Engineering
Samuel Zhou: Boston University, Department of Biomedical Engineering
Rebecca A. Mount: Boston University, Department of Biomedical Engineering
Yangyang Wang: Boston University, Department of Biomedical Engineering
Cara R. Ravasio: Boston University, Department of Biomedical Engineering
Xue Han: Boston University, Department of Biomedical Engineering

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Deep brain stimulation (DBS) is a promising neuromodulation therapy, but the neurophysiological mechanisms of DBS remain unclear. In awake mice, we performed high-speed membrane voltage fluorescence imaging of individual hippocampal CA1 neurons during DBS delivered at 40 Hz or 140 Hz, free of electrical interference. DBS powerfully depolarized somatic membrane potentials without suppressing spike rate, especially at 140 Hz. Further, DBS paced membrane voltage and spike timing at the stimulation frequency and reduced timed spiking output in response to hippocampal network theta-rhythmic (3–12 Hz) activity patterns. To determine whether DBS directly impacts cellular processing of inputs, we optogenetically evoked theta-rhythmic membrane depolarization at the soma. We found that DBS-evoked membrane depolarization was correlated with DBS-mediated suppression of neuronal responses to optogenetic inputs. These results demonstrate that DBS produces powerful membrane depolarization that interferes with the ability of individual neurons to respond to inputs, creating an informational lesion.

Date: 2022
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DOI: 10.1038/s41467-022-35314-1

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