Memory and Cognition-Related Neuroplasticity Enhancement by Transcranial Direct Current Stimulation in Rodents: A Systematic Review

Abstract

Brain stimulation techniques, including transcranial direct current stimulation (tDCS), were identified as promising therapeutic tools to modulate synaptic plasticity abnormalities and minimize memory and learning deficits in many neuropsychiatric diseases. Here, we revised the effect of tDCS on the modulation of neuroplasticity and cognition in several animal disease models of brain diseases affecting plasticity and cognition. Studies included in this review were searched following the terms ("transcranial direct current stimulation") AND (mice OR mouse OR animal) and according to the PRISMA statement requirements. Overall, the studies collected suggest that tDCS was able to modulate brain plasticity due to synaptic modifications within the stimulated area. Changes in plasticity-related mechanisms were achieved through induction of long-term potentiation (LTP) and upregulation of neuroplasticity-related proteins, such as c-fos, brain-derived neurotrophic factor (BDNF), or N-methyl-D-aspartate receptors (NMDARs). Taken into account all revised studies, tDCS is a safe, easy, and noninvasive brain stimulation technique, therapeutically reliable, and with promising potential to promote cognitive enhancement and neuroplasticity. Since the use of tDCS has increased as a novel therapeutic approach in humans, animal studies are important to better understand its mechanisms as well as to help improve the stimulation protocols and their potential role in different neuropathologies.

Figure 1

Illustration of transcranial direct current stimulation in the mice. Anodal stimulation depolarizes the neuronal membrane and enhances excitability. On the other hand, cathodal stimulation hyperpolarizes the neuronal membrane and decreases excitability.

Figure 2

Search flow diagram (in accordance with PRISMA statement). Abbreviations: DB: deep brain stimulation; tACS: transcranial alternating current stimulation; TMS: transcranial magnetic stimulation.

Figure 3

Schematic illustration of molecular mechanisms underlying the effect of anodal transcranial direct current stimulation (tDCS) on neuronal physiology. The neurostimulation in the target cortical area depolarizes neuronal membrane and glutamate released in presynaptic neuron and binds in NMDA and AMPA receptors (see book chapter Rozisky et al., 2015). Consequently, there is intracellular Ca²⁺ upregulation in the postsynaptic neuron, which can activate protein kinases that in turn modulate numerous neuronal signaling pathways (such as the mTOR pathway) leading to transcriptional changes. The tDCS also activates molecular cascades to promote BDNF production. As a long-term mechanism, gene transcription is modulated leading to the formation of new proteins that in turn lead to facilitation of LTP and improvement of cognition. Abbreviations: AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; BDNF: brain-derived neurotrophic factor; CBP: CREB-binding protein; CREB: cAMP response element binding protein; GSK3: glycogen synthase kinase 3; LTP: long-term potentiation; mTOR: mammalian target of rapamycin; NMDA: N-methyl-D-aspartate; TrkB: tropomyosin receptor kinase B.