Contribution of axonal orientation to pathway-dependent modulation of excitatory transmission by direct current stimulation in isolated rat hippocampus

Abstract

Transcranial direct current stimulation (tDCS) is a method for modulating cortical excitability by weak constant electrical current that is applied through scalp electrodes. Although often described in terms of anodal or cathodal stimulation, depending on which scalp electrode pole is proximal to the cortical region of interest, it is the orientation of neuronal structures relative to the direct current (DC) vector that determines the effect of tDCS. To investigate the contribution of neural pathway orientation, we studied DCS-mediated neuromodulation in an in vitro rat hippocampal slice preparation. We examined the contribution of dendritic orientation to the direct current stimulation (DCS) neuromodulatory effect by recording field excitatory postsynaptic potentials (fEPSPs) in apical and basal dendrites of CA1 neurons within a constant DC field. In addition, we assessed the contribution of axonal orientation by recording CA1 and CA3 apical fEPSPs generated by stimulation of oppositely oriented Schaffer collateral and mossy fiber axons, respectively, during DCS. Finally, nonsynaptic excitatory signal propagation was measured along antidromically stimulated CA1 axons at different DCS amplitudes and polarity. We find that modulation of both the fEPSP and population spike depends on axonal orientation relative to the electric field vector. Axonal orientation determines whether the DC field is excitatory or inhibitory and dendritic orientation affects the magnitude, but not the overall direction, of the DC effect. These data suggest that tDCS may oppositely affect neurons in a stimulated cortical volume if these neurons are excited by oppositely orientated axons in a constant electrical field.

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

“…Thus, concurrent tDCS applied to the somatosensory cortex was capable of increasing or decreasing the amplitude and area of LFPs evoked by the simultaneous air puff stimulation of the whisker pad. Moreover, tDCS had a persistent poststimulus effect; the inhibitory effect of 1 mA of cathodal tDCS on N1 amplitude was significantly [F (7,28,760) = 16.943; P < 0.001, repeated-measures ANOVA] evident for up to 30 min after the end of the DC stimulation (Fig. 1D).…”

Acute and repetitive fronto-cerebellar tDCS stimulation improves mood in non-depressed participants

“…Datta et al 2009), this is perhaps somewhat over-simplistic. Orientation of somatodendritic axis and the distance of the axon to the locally applied direct current has resulting cellular influences (Holsheimer et al 2007;Bikson et al 2004;Gluckman et al 1996) and can determine whether the applied field has an excitatory or inhibitory influence (Kabakov et al 2012). Additionally, the physiological effects of the stimulation extend beyond the influence of electrode polarity and neuronal orientation and are also determined by whether the predominant influence of the affected network is excitatory or inhibitory .…”

Efficacy of Transcranial Direct Current Stimulation as Support for Neurorehabilitation Therapy: A Meta-analysis of Available Studies

“…In a particular way the Long Term Potentiation mechanism determines a long-term increase of synapse efficiency, and long-term depression (LTD) translated in a diminution in synapse efficiency, are mechanisms that occur in the cerebral cortex and are strongly implicated as a primary factor in motor learning and brain plasticity, this could clarify the effects of tDCS [24]. The explanation derives from the assertion for which NMDA receptor modulation plays an important role for the propagation of LTP and LTD, bringing a facilitation when the post-synaptic membranes, soma and dendritic are depolarized [25], when the area underlying the stimulation is closer to the negative pole of the electric field, facilitates the opening of voltagedependent ionic channels with consequent activation of the NMDA receptors by removing the magnesium ions block Mg + [26]. Anodal stimulation could therefore activate the NMDA receptors, potentially translating into a significant increase of Ca 2+ in post-synaptic cells [23]; it is therefore hypothesized that facilitation in motor learning through repeated tDCS sessions can be explained as the result of an additional effect on the post-synaptic levels of Ca 2+ , which leads to a long-term change in synaptic efficiency [23].…”