Selective gating of neural modulation through frequency- and behavior-dependent modes during cortical electrical stimulation
Electrical stimulation is widely used to modulate neuronal activity, yet its effects on neuronal circuits in vivo remain poorly understood. This, in turn, has hindered the principled design of stimulation protocols and raised questions about reproducibility that constrain the field's translational impact. Here we combine cortical sinusoidal electrical stimulation (sES) with Neuropixels recordings…
Stimulation of the brain using electrical currents is a technique used to influence how neurons communicate with each other. However, the specifics of how this method affects neural activity in living animals is not fully understood, which has limited the development of effective, reliable stimulation protocols.
In this study, researchers employed a technique called cortical sinusoidal electrical stimulation (sES) to examine its impact on the activity of thousands of well-isolated neurons in various areas of the brain from 14 mice while the animals were behaving and fixed in place. By recording the responses of these neurons, the team discovered two distinct modes of neural modulation that occur simultaneously when the brain is stimulated.
The first mode involves a long-lasting effect where the stimulation frequency determines how the neurons respond. At slower stimulation rates, the electric field generated by the stimulation spreads out in a non-synaptic manner, synchronizing the timing of spikes across the brain. In contrast, at higher stimulation frequencies, the anatomical connections between neurons dominate the response, entraining the neurons to the stimulation rhythm.
The second mode is a short-lived effect that mainly affects the timing of individual spikes within specific brain regions. This effect is mediated through the anatomical connections and only becomes apparent when the stimulation frequency is high. Interestingly, this mode selectively recruits inhibitory neurons, which help to suppress neuronal activity.
The researchers also found that behavior plays a crucial role in shaping these two distinct modes of neural modulation. High stimulation frequencies cause brain-wide entrainment, but this effect is not seen when the animals are passive. Conversely, spatially localized spike-rate modulation is only observed during active behavior.
By understanding the different ways that cortical electrical stimulation can influence neural activity, this study provides a foundation for designing stimulation protocols that are both targeted and reproducible. This could pave the way for more effective neuromodulation strategies in the future.
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