Effects of direct current stimulation on synaptic plasticity in a single neuron

Abstract

Background: Transcranial direct current stimulation (DCS) has lasting effects that may be explained by a boost in synaptic long-term potentiation (LTP). We hypothesized that this boost is the result of a modulation of somatic spiking in the postsynaptic neuron, as opposed to indirect network effects. To test this directly we record somatic spiking in a postsynaptic neuron during LTP induction with concurrent DCS. Methods: We performed rodent in-vitro patch-clamp recordings at the soma of individual CA1 pyramidal neurons. LTP was induced with theta-burst stimulation (TBS) applied concurrently with DCS. To test the causal role of somatic polarization, we manipulated polarization via current injections. We also used a computational multi-compartment neuron model that captures the effect of electric fields on membrane polarization and activity-dependent synaptic plasticity. Results: TBS-induced LTP was enhanced when paired with anodal DCS as well as depolarizing current injections. In both cases, somatic spiking during the TBS was increased, suggesting that evoked somatic activity is the primary factor affecting LTP modulation. However, the boost of LTP with DCS was less than expected given the increase in spiking activity alone. In some cells, we also observed DCS-induced spiking, suggesting DCS also modulates LTP via induced network activity. The computational model reproduces these results and suggests that they are driven by both direct changes in postsynaptic spiking and indirect changes due to network activity. Conclusion: DCS enhances synaptic plasticity by increasing postsynaptic somatic spiking, but we also find that an increase in network activity may boost but also limit this enhancement.

Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning

“…Whatever the mechanism, they are likely to operate at higher field intensities as well. However, when strong fields are used, network activity may be induced which limits further potentiation via homeostatic mechanisms consistent with previous reports [12,15]. In summary, stimulation at physiological levels may conspire to optimally benefit from the cumulative effects of repeated TBS while extending the ceiling of LTP with weak DCS.…”

“…by blocking the SK channels using apamine [44,45,56]) or using intracellular recordings during DCS (as in Ref. [15]). Whatever the mechanism, they are likely to operate at higher field intensities as well.…”

“…Many in-vitro studies confirm the LTP boosting effect of anodal DCS [12e17]. While that may be true, these in-vitro studies use electric fields in the range of 20 V/m or above [12,13,15,17]. Conventional tDCS in humans uses 2 mA current that generates electric fields in the brain of less than 1 V/m [20].…”

Calcium channels control tDCS-induced spontaneous vesicle release from axon terminals

“…This can delineate how even a small prolonged subthreshold stimulus is proficient in producing significant cognitive and behavioral J o u r n a l P r e -p r o o f 20 changes by modulating presynaptic spontaneous activity. Considering each synapse as a node in the neuronal network, a modification in synaptic vesicle release from a group of axons that is oriented in a laminar fashion can drastically alter the ongoing synaptic plasticity (Farahani et al, 2021;Vasu and Kaphzan, 2021). This comprehension of the cellular effects of tDCS has the potential to enable the optimization of tDCS application using pharmacological augmentation (Chakraborty et al, 2017;Das et al, 2016;Nitsche et al, 2007;Vasu and Kaphzan, 2021).…”

In vivo Measurements of Electric Fields During Cranial Electrical Stimulation in the Human Brain

“…The CES-induced spatial electric fields (EFs) within the corresponding brain regions are likely a significant factor for the biological effects of CES. Several studies have provided evidence for the effects of EFs on neural activity (Sun et al, 2016;Kronberg et al, 2020;Farahani et al, 2021). However, it is extremely difficult to obtain the EF distributions directly from live human brains during the stimulation process.…”