Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits
- Javier Márquez-Ruiza,
- Rocío Leal-Campanarioa,
- Raudel Sánchez-Campusanoa,
- Behnam Molaee-Ardekanib,c,
- Fabrice Wendlingb,c,
- Pedro C. Mirandad,
- Giulio Ruffinie,
- Agnès Gruarta, and
- José María Delgado-Garcíaa,1
+ Author Affiliations
- aDivision of Neurosciences, Pablo de Olavide University, 41013 Seville, Spain;
- bInstitut National de la Santé et de la Recherche Médicale U642, Rennes F-35000, France;
- cLaboratoire Traitement du Signal et de L'Image, Université de Rennes 1, Rennes F-35000, France;
- dNeuroelectrics, 08022 Barcelona, Spain; and
- eStarlab Barcelona SL, 08022 Barcelona, Spain
- Edited* by Ivan Izquierdo, Centro de Memoria, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil, and approved March 20, 2012 (received for review December 21, 2011)
Transcranial direct-current stimulation (tDCS) is a noninvasive brain stimulation technique that has been successfully applied for modulation of cortical excitability. tDCS is capable of inducing changes in neuronal membrane potentials in a polarity-dependent manner. When tDCS is of sufficient length, synaptically driven after-effects are induced. The mechanisms underlying these after-effects are largely unknown, and there is a compelling need for animal models to test the immediate effects and after-effects induced by tDCS in different cortical areas and evaluate the implications in complex cerebral processes. Here we show in behaving rabbits that tDCS applied over the somatosensory cortex modulates cortical processes consequent to localized stimulation of the whisker pad or of the corresponding area of the ventroposterior medial (VPM) thalamic nucleus. With longer stimulation periods, poststimulation effects were observed in the somatosensory cortex only after cathodal tDCS. Consistent with the polarity-specific effects, the acquisition of classical eyeblink conditioning was potentiated or depressed by the simultaneous application of anodal or cathodal tDCS, respectively, when stimulation of the whisker pad was used as conditioned stimulus, suggesting that tDCS modulates the sensory perception process necessary for associative learning. We also studied the putative mechanisms underlying immediate effects and after-effects of tDCS observed in the somatosensory cortex. Results when pairs of pulses applied to the thalamic VPM nucleus (mediating sensory input) during anodal and cathodal tDCS suggest that tDCS modifies thalamocortical synapses at presynaptic sites. Finally, we show that blocking the activation of adenosine A1 receptors prevents the long-term depression (LTD) evoked in the somatosensory cortex after cathodal tDCS.
- Author contributions: J.M.-R., R.L.-C., G.R., A.G., and J.M.D.-G. designed research; J.M.-R., R.L.-C., A.G., and J.M.D.-G. performed research; R.S.-C., B.M.-A., F.W., and P.C.M. contributed new reagents/analytic tools; R.S.-C., B.M.-A., and P.C.M. analyzed data; and J.M.-R., G.R., A.G., and J.M.D.-G. wrote the paper.
- The authors declare no conflict of interest.
- ↵*This Direct Submission article had a prearranged editor.
- This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1121147109/-/DCSupplemental.
Freely available online through the PNAS open access option.