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Subthreshold electric fields bidirectionally modulate neurotransmitter release through axon polarization.

Aman S Aberra1, Madelyn W Miles1, Michael B Hoppa1

  • 1Dept. of Biological Sciences, Dartmouth College, Hanover, NH, USA.

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|December 18, 2025
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Summary

Subthreshold electric fields significantly impact neurotransmitter release by altering presynaptic calcium levels and vesicle dynamics. These findings offer new insights into neuromodulation therapies.

Keywords:
Hippocampal neuronsNeurotransmissionSubthreshold electric fieldsSynapseSynaptic plasticityTranscranial direct current stimulation

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Area of Science:

  • Neuroscience
  • Biophysics

Background:

  • Subthreshold electric fields modulate brain activity for therapeutic applications.
  • Non-uniform neuronal membrane polarization occurs despite uniform electric fields.
  • Axonal polarization and its effect on neurotransmitter release remain unquantified.

Purpose of the Study:

  • Investigate how subthreshold electric fields affect synaptic function.
  • Utilize advanced optogenetic indicators for high-resolution measurements.

Main Methods:

  • Combined optogenetic indicators for voltage, glutamate, and calcium.
  • Studied subcellular responses in single neurons with high spatiotemporal resolution.

Main Results:

  • Mapped membrane polarization profiles from uniform electric fields in neurons.
  • Observed significant neurotransmitter release modulation by clinically relevant electric fields (<5 mV polarization).
  • Identified altered resting calcium levels and synaptic vesicle participation as key mechanisms.

Conclusions:

  • Directly measured electric field effects on axonal and synaptic function using optical methods.
  • Overcame limitations of traditional electrophysiology.
  • Provided cellular mechanism insights for subthreshold electric field stimulation and neuromodulation therapy design.