Direct current stimulation induces mGluR5 ‐dependent neocortical plasticity

ObjectiveTo obtain insights into mechanisms mediating changes in cortical excitability induced by cathodal transcranial direct current stimulation (tDCS).
MethodsNeocortical slices were exposed to direct current stimulation (DCS) delivered through Ag/AgCl electrodes over a range of current orientations, magnitudes, and durations. DCS‐induced cortical plasticity and its receptor dependency were measured as the change in layer II/III field excitatory postsynaptic potentials by a multielectrode array, both with and without neurotransmitter receptor blockers or allosteric modulators. In vivo, tDCS was delivered to intact mice scalp via surface electrodes. Molecular consequences of DCS in vitro or tDCS in vivo were tested by immunoblot of protein extracted from stimulated slices or the neocortex harvested from stimulated intact mice.
ResultsCathodal DCS in vitro induces a long‐term depression (DCS‐LTD) of excitatory synaptic strength in both human and mouse neocortical slices. DCS‐LTD is abolished with an mGluR5 negative allosteric modulator, mechanistic target of rapamycin (mTOR) inhibitor, and inhibitor of protein synthesis. However, DCS‐LTD persists despite either γ‐aminobutyric acid type A receptor or N‐methyl‐D‐aspartate receptor inhibition. An mGluR5‐positive allosteric modulator, in contrast, transformed transient synaptic depression resultant from brief DCS application into durable DCS‐LTD.
InterpretationWe identify a novel molecular pathway by which...

Source: Annals of Neurology - July 6, 2016 Category: Neurology Authors: Yan Sun, Jonathan O. Lipton, Lara M. Boyle, Joseph R. Madsen, Marti C. Goldenberg, Alvaro Pascual ‐Leone, Mustafa Sahin, Alexander Rotenberg Tags: Research Article Source Type: research