Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits

Abstract

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 aftereffects 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.T he effects of weak direct-current (DC) stimulation on the excitability of the central nervous system were reported decades ago. Invasive stimulation in acute animals demonstrated that intracortical or epidural application of weak DC induces polarityspecific changes in the neuronal excitability of motor (1, 2), visual (1), and somatosensory (3) cortices. Interestingly, these changes persist for several minutes after the DC stimulus offset (3), sharing some molecular mechanisms with the classical long-term plasticity. In this regard, it has been demonstrated that anodal DC stimulation applied on the rat sensorimotor cortex modifies adenosine-elicited accumulation of cAMP (4), inducing an increase of protein kinase C and calcium levels (5, 6). tDCS has been successfully applied for modulation of cortical excitability in humans (7-11), and interest is growing in the use of this technique as a noninvasive tool for basic and clinical research in various neurologic pathologies, including chronic pain, stroke, and depression (12-15). Little is known about the molecular and/or cellular mechanisms underlying the neuromodulatory after-effects of tDCS, however. For this reason, new experimental models...

Direct current stimulation modulates LTP and LTD: activity dependence and dendritic effects

“…Asymmetries have been found in other animal studies [10], [13] and human studies [1], [50]. In parallel work in our lab, we find an asymmetry in acute DCS effects on cellular excitability.…”

Transcranial Current Brain Stimulation (tCS): Models and Technologies

“…Recent work by Marquez-Ruiz et al in behaving rabbits has shown that tDCS modulates cortical processes and leads to after effects with longer stimulation periods [146]. 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.…”

Beyond the silence: Bilateral somatosensory stimulation enhances skilled movement quality and neural density in intact behaving rats

“…Using a complementary approach to inducing focal cortical lesions, we applied anodal transcranial direct current stimulation (tDCS) over S1 in intact behaving rats. The procedure that delivered subthreshold electrical current to the S1 region was used because tDCS can focally affect the level of hemispheric excitability and modulate spontaneous neuronal activity in a polarity-dependent manner [17,18]. Cortical excitability, therefore, can be either increased by anodal stimulation or decreased by cathodal stimulation [19].…”