Abstract
Background: Transcranial direct current stimulation (tDCS) is a subthreshold neurostimulation therapeutic method that ameliorate neuropsychiatric impairments. The most sensitive subcellular compartment for tDCS are the axons that polarize. However, how these relatively small polarizations significantly alter synaptic dynamics is still unknown. Objective/Hypothesis: We hypothesized that tDCS-induced axonal polarization modulates calcium channel activity at the presynaptic compartment, thus playing a crucial role in synaptic vesicle release. Methods: For this aim, we examined how different DCS conditions and orientations affect the spontaneous excitatory post synaptic currents (sEPSCs) recorded from hippocampal CA1 pyramidal neurons. Since P/Q-type calcium-channels are the main presynaptic voltage-dependent calcium-channels in the hippocampus, we further examined the DCS effects while applying a P/Q-type calcium channels blocker, ω-agatoxin. Additionally, to explain the DCS-induced calcium channel-regulated vesicle release dynamics, we developed a simplified model to complement our experimental results. Results: We demonstrated that anodal-DCS application in a dorso-ventral orientation, similar to that of in-vivo experiments, enhanced the sEPSCs frequency, while cathodal-DCS was ineffective. Moreover, DCS application in parallel to the Schaffer collaterals (medio-lateral orientation), showed both anodal and cathodal significant effects. Furthermore, the ω-agatoxin application occluded the DCS-induced modulation of sEPSC frequencies in any orientation. The model showed the interaction between DCS-induced membrane polarization, calcium channel activation and presynaptic vesicle release. Conclusion: Using experiments and modeling we show that DCS induces a small variation in terminal membrane potential sufficient to activate P/Q type voltage-gated calcium channels, and that this is sufficient to modify presynaptic calcium concentration, subsequently altering spontaneous vesicle release.
Original language | English |
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Pages (from-to) | 270-282 |
Number of pages | 13 |
Journal | Brain Stimulation |
Volume | 15 |
Issue number | 1 |
DOIs | |
State | Published - 1 Jan 2022 |
Bibliographical note
Funding Information:The work was supported by the Israel Science Foundation Grant No. 248/20 (HK) .
Publisher Copyright:
© 2022
Keywords
- Axon terminals
- Calcium channels
- Enhanced polarization
- Subthreshold
- Weak electrical fields
- tDCS
ASJC Scopus subject areas
- General Neuroscience
- Biophysics
- Clinical Neurology