Presynaptic actions of transcranial and local direct current stimulation in the red nucleus

Key points Transcranial direct current stimulation (tDCS) may affect both postsynaptic neurons and presynaptic axons providing input to these neurons. Here, we show that presynaptic subcortical actions of tDCS outlast the duration of its application by up to 1 h and may contribute to long‐lasting facilitation of activation of neurons in the red nucleus in experiments on deeply anaesthetized animals. This is demonstrated by increased axonal excitability of the interpositorubral neurons that, in turn, activate rubrospinal neurons. We also show that effects of electric fields induced by tDCS may be reproduced by local cathodal polarization, by applying <1 μA direct current within the red nucleus. Such polarization replicates effects of anodal tDCS in the cat as well as cathodal tDCS in the rat and evokes similar long‐lasting facilitation. Abstract The main aim of the present study was to examine to what extent long‐lasting subcortical actions of transcranial direct current stimulation (tDCS) may be related to its presynaptic actions. This was investigated in the red nucleus, where tDCS was recently demonstrated to facilitate transmission between interpositorubral and rubrospinal neurons. Changes in the excitability of preterminal axonal branches of interpositorubral neurons close to rubrospinal neurons were investigated during and after tDCS (0.2 mA) applied over the sensorimotor cortical area in deeply anaesthetized rats and cats. As a measure of the excitability, we used the probability of antidromic activation of individual interpositorubral neurons by electrical stimuli applied in the red nucleus. Our second aim was to compare effects of weak (≤1 μA) direct current applied within the red nucleus with effects of tDCS to allow the use of local depolarization in a further analysis of mechanisms of tDCS instead of widespread and more difficult to control depolarization evoked by distant electrodes. Local cathodal polarization was found to replicate all effects of cathodal tDCS hitherto demonstrated in the rat, including long‐lasting facilitation of trans‐synaptically evoked descending volleys and trisynaptically evoked EMG responses in neck muscles. It also replicated all effects of anodal tDCS in the cat. In both species, it increased the excitability of preterminal axonal branches of interpositorubral neurons up to 1 h post‐tDCS. Local anodal polarization evoked opposite effects. We thus show that presynaptic actions of polarizing direct current may contribute to both immediate and prolonged effects of tDCS.