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

Area of Science:

• Neuroscience
• Neuromodulation
• Cellular Electrophysiology

Background:

• Deep brain stimulation (DBS) is an emerging neuromodulation therapy.
• The precise neurophysiological mechanisms underlying DBS efficacy remain largely unknown.

Purpose of the Study:

• To investigate the direct effects of DBS on the membrane potential and spiking activity of individual hippocampal neurons.
• To elucidate the cellular mechanisms by which DBS influences neuronal information processing.

Main Methods:

• High-speed membrane voltage fluorescence imaging was employed in awake mice.
• Individual hippocampal CA1 neurons were monitored during DBS at 40 Hz and 140 Hz.
• Optogenetic stimulation was used to evoke theta-rhythmic inputs to assess neuronal responses under DBS.

Main Results:

• DBS induced significant somatic membrane depolarization in hippocampal neurons, particularly at 140 Hz.
• DBS synchronized membrane voltage and spiking activity to the stimulation frequency.
• DBS reduced the neurons' ability to respond to theta-rhythmic network activity and optogenetically evoked inputs.
• DBS-evoked depolarization correlated with suppressed neuronal responses to synaptic inputs.

Conclusions:

• Deep brain stimulation directly causes profound membrane depolarization in individual neurons.
• This depolarization interferes with the cellular processing of synaptic inputs, effectively creating an informational lesion.
• These findings offer critical insights into the neurophysiological underpinnings of DBS therapy.