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Direct current stimulation boosts synaptic gain and cooperativity in vitro.

Asif Rahman1, Belen Lafon1, Lucas C Parra1

  • 1Department of Biomedical Engineering, The City College of The City University of New York, Steinman Hall, 160 Convent Ave, New York, NY, 10031, USA.

The Journal of Physiology
|April 25, 2017
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Summary

Direct current stimulation (DCS) can enhance brain connectivity by polarizing neurons and axons, even with synaptic depression. This neuromodulation, particularly effective with transcranial direct current stimulation (tDCS), boosts communication between co-active brain regions.

Keywords:
electrical brain stimulationsynaptic depressiontranscranial direct current stimulation

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Area of Science:

  • Neuroscience
  • Computational Neuroscience
  • Biophysics

Background:

  • Transcranial direct current stimulation (tDCS) causes sustained, diffuse brain current flow with effects outlasting stimulation.
  • The precise mechanisms by which tDCS modulates synaptic dynamics and afferent inputs remain unclear.
  • Understanding tDCS effects requires models capturing its spatiotemporal features and state-dependent outcomes.

Purpose of the Study:

  • To investigate how direct current stimulation (DCS) affects synaptic efficacy during continuous presynaptic input.
  • To elucidate the roles of postsynaptic and afferent axon polarization in DCS-mediated neuromodulation.
  • To explore how the diffuse nature of tDCS current flow can enhance connectivity between co-active brain regions.

Main Methods:

  • Acute DCS (10-20 V m⁻¹) applied during constant rate (5-40 Hz) and Poisson-distributed (4 Hz mean) presynaptic input trains.
  • Quantification of synaptic depression and DCS sensitivity (1.1% to 0.55% per V m⁻¹).
  • Multiscale modeling integrating finite element method (FEM) for current flow, neuronal activity simulations, and statistical theory of coincident activity.

Main Results:

  • DCS demonstrated polarity-specific modulation of sustained synaptic activity across tested frequencies.
  • Synaptic depression reduced DCS sensitivity, but DCS facilitated cumulative neuromodulation, potentially reversing depression.
  • DCS effects were mediated by both postsynaptic and afferent axon polarization, enhancing synaptic cooperativity.

Conclusions:

  • DCS, through polarizing neurons and axons, modulates synaptic efficacy and boosts cooperativity between inputs.
  • Polarization of afferent neurons in upstream regions may influence activity in target brain regions during tDCS.
  • The diffuse, weak, and sustained nature of tDCS is advantageous for enhancing connectivity between co-active brain regions.