OP 8. Modulating tactile perception and learning processes by tCS in animal models: Hyperinteraction viability experiments (HIVE)

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The mission of the European HIVE (Hyperinteraction viability experiments) project is to develop new stimulation paradigms and to create a new generation of non-invasive brain stimulation technologies. The transcranial current stimulation (tCS) is a non-invasive brain stimulation technique that has been successfully applied in both basic and clinical researches. Whereas transcranial direct-current stimulation (tDCS) is capable of inducing changes in neuronal membrane potentials in a polarity-dependent way, transcranial alternating-current stimulation (tACS) has been proposed to interact with ongoing cortical oscillations enhancing or diminishing specific frequencies of cortical neural activities. Nevertheless, little is known about tCS effects on cortical circuits and its implications in sensory perception processes. The aim of the HIVE project is to investigate the biophysics of non-invasive brain stimulation at the theoretical, computational and experimental level – both in humans and animals. Specifically, the objective of this study was to investigate tDCS effects on the plastic properties of the somatosensory cortex, to provide a new animal model to study the effects of tCS in learning, and to test for the viability of hyperinteraction experiments, implying the direct generation of perceptions and, hence, transmission of information, by transcranial stimulation of the cerebral cortex. Rabbits were prepared for the chronic recording of local field potentials (LFP) in the somatosensory cortex (SS) in response to whisker and/or ventroposterior medial (VPM) thalamic nucleus stimulations in the presence of tDCS and tACS. A second group of animals was prepared for classical eyeblink conditioning and simultaneous tCS. tDCS and tACS applied over the SS modulated cerebral cortical processes subsequent to the localized stimulation of the whisker pad or of the corresponding area of the VPM nucleus. Longer stimulation periods indicate that post-stimulation effects were only observed in the SS after cathodal tDCS. Consistently with this polarity-specific effects, the acquisition of a classical eyeblink conditioning was potentiated or depressed by the application of anodal or cathodal tDCS respectively, when stimulation of whisker pad was used as a conditioned stimulus (CS). In addition, we noticed that tACS (100 ms, 30 Hz) can successfully substitute for whisker CS during an associative learning task. tACS-CS induced conditioned responses similar to those observed when a direct stimulation of the whisker pad was carried out. We also studied the putative mechanisms underlying immediate and after-effect of tDCS observed in the SS. Pairs of pulses applied to the thalamic VPM nucleus suggested that tDCS modifies thalamocortical synapses at presynaptic sites. In addition, blocking activation of adenosine A1 receptors prevented the long-term depression evoked in the SS following cathodal tDCS. Results reported here confirm earlier studies in humans regarding the effects of tDCS and tACS on the cerebral cortex, highlighting the potential of this technique for modulating associative learning. In addition, it is shown the participation of adenosine A1 receptors in tDCS actions on cortical circuits. We also show that peripheral whisker stimulation can be substituted by tACS as CS when the proper stimulation frequencies are applied. Supported by grants BFU2011-29089, P07-CVI-02487 to J.M.D.-G., and BFU2011-29286, P07-CVI-02686 to A.G., from Spain. In addition, this work was funded by the EU FP7 FET-Open HIVE (222079) Project.