Modulating Hippocampal Plasticity withIn VivoBrain Stimulation

Abstract

Investigations into the use of transcranial direct current stimulation (tDCS) in relieving symptoms of neurological disorders and enhancing cognitive or motor performance have exhibited promising results. However, the mechanisms by which tDCS effects brain function remain under scrutiny. We have demonstrated that in vivo tDCS in rats produced a lasting effect on hippocampal synaptic plasticity, as measured using extracellular recordings. Ex vivo preparations of hippocampal slices from rats that have been subjected to tDCS of 0.10 or 0.25 mA for 30 min followed by 30 min of recovery time displayed a robust twofold enhancement in long-term potentiation (LTP) induction accompanied by a 30% increase in paired-pulse facilitation (PPF). The magnitude of the LTP effect was greater with 0.25 mA compared with 0.10 mA stimulations, suggesting a dose-dependent relationship between tDCS intensity and its effect on synaptic plasticity. To test the persistence of these observed effects, animals were stimulated in vivo for 30 min at 0.25 mA and then allowed to return to their home cage for 24 h. Observation of the enhanced LTP induction, but not the enhanced PPF, continued 24 h after completion of 0.25 mA of tDCS. Addition of the NMDA blocker AP-5 abolished LTP in both control and stimulated rats but maintained the PPF enhancement in stimulated rats. The observation of enhanced LTP and PPF after tDCS demonstrates that non-invasive electrical stimulation is capable of modifying synaptic plasticity.

Animal models of transcranial direct current stimulation: Methods and mechanisms

“…LTP/LTD induced by either tetanic stimulation or DC may, unsurprisingly, share some common molecular substrates (Gartside, 1968b, Islam et al, 1995b, Ranieri et al, 2012, Rohan et al, 2015). Common forms of LTP/LTD are mediated by the NMDA receptor (Malenka et al, 2004), which has been implicated in lasting tDCS effects in both humans (Nitsche et al, 2003a) and rodents in vivo (Rohan et al, 2015), and in vitro DCS-induced plasticity (Fritsch et al, 2010).…”

“…Common forms of LTP/LTD are mediated by the NMDA receptor (Malenka et al, 2004), which has been implicated in lasting tDCS effects in both humans (Nitsche et al, 2003a) and rodents in vivo (Rohan et al, 2015), and in vitro DCS-induced plasticity (Fritsch et al, 2010). Similarly, the BDNF/TrKB pathway can be a potent modulator of these common forms of LTP/LTD (Lu, 2003), and this pathway has also been implicated in lasting tDCS effects in both humans and in vitro (Fritsch et al, 2010, Ranieri et al, 2012).…”

“…Another recent model using rodents studied anodal tDCS in vivo by evaluating synaptic effects ex vivo , showing enhanced NMDA receptor activation dependent LTP after a single 30 minute anodal tDCS session, remarkably persisting for at least 24 hours. They also showed anodal DCS enhanced the paired pulse facilitation (PPF) ratio independent of NMDAR activation, suggesting effects of tDCS on LTP may have presynaptic origins (Rohan et al, 2015). …”

Optimizing Transcranial Direct Current Stimulation Protocols to Promote Long-Term Learning

“…A n u m b e r o f a n i m a l s t u d i e s h a v e m e a s u r e d polarity-dependent cellular changes in LTP both in vitro (Ranieri et al 2012;Ruohonen and Karhu 2012) and in vivo (Podda et al 2016;Rohan et al 2015) as a function of direct current stimulation. Analogously, human experiments have demonstrated on a behavioral level that tDCS over multiple days can lead to cumulative effects between sessions, suggesting the existence of continued offline processes between each bout of stimulation.…”

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

“…Despite the common practice of applying tDCS during training, cellular effects of DCS applied during endogenous plasticity induction remain largely unexplored. Instead, the majority of research has analyzed effects when DCS precedes plasticity induction [9]- [11], or is paired with endogenous activity otherwise not known to induce plasticity [12]- [14]. Here we are interested in the effects of DCS applied during training, i.e.…”