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

Table 4

Cellular and molecular mechanisms underlying transcranial direct current stimulation effect in the brain.

Author

Year

Animal model

Specimen; gender

Stimulation parameters

Main findings

Stimulation electrode

Reference electrode

Anesthesia

rtDCS

Polarity

Position

Stimulation intensity (mA)

Size (cm^2)

Stimulation duration (min)

Current density (A/m^2)

Position

Area (cm^2)

Márquez-Ruiz et. [63]

2012

NDM

New Zealand White albino rabbits; N/A

13

a-tDCS and c-tDCS

Somatosensory cortex (S1)

0.5; 1; 1.5 and 2

0.7857

10

3.7

Ear

35

N

N (single session)

↑ LFP in S1 (a-tDCS) and ↓ LFP S1 (c-tDCS)

Rohan et al. [57]

2015

NDM

Sprague Dawley rats; male

34

a-tDCS

SC dorsal to the hippocampus

0.1 or 0.25

0.25

30

N/A

Between shoulders

8.04

N

N (single session)

# LTP and PPF in the hippocampus

Yoon et al. [31]

2016

Lateral fluid percussion method

Sprague Dawley rats; males

36

a-tDCS

Hippocampus

0.2

0.0225

20

28.2

Chest

48 (corset)

Y

Y (daily for 5 days)

# perilesional area BDNF expression (tDCS 2 weeks post-TBI); # choline/creatinine ratios (tDCS 1 week post-TBI); Motor performance recovery (2 weeks of tDCS)

Leffa et al. [33]

2016

SHR

SHR rats and WKT rats; males

48

a-tDCS

Frontal cortex

0.5

1.5

20

33.4

Between ears

1.5

N

Y (8 consecutive days

# DA levels in STR in both rat strains and in the hippocampus following tDCS treatment in WKY; # BDNF levels in WKY rats; Short-term memory improvement

Podda et al. [40]

2016

NDM

C57BL/6 mice; males

16

a-tDCS vs. c-tDCS

Left parietal cortex (dorsal to hippocampal formation)

0.35

0.06

20

N/A

Ventral thorax

5.2

N

N (single session)

# spatial learning and memory (a-tDCS); benefits observable one week after; # BDNF expression in the hippocampus; CREB/CBP pathway activation

Monai et al. [75]

2016

NDM

G7NG817 mice; N/A

10

a-tDCS

Primary visual cortex (VI)

0.1

0.02

10

N/A

Neck

N/A

N

N (single session)

Up to 50% expansion of visual evoke active area (up to 2 h poststimulation effect); tDCS-induced plasticity depends on the activity of IP, R2, and A1AR

Kim et al. [78]

2017

NDM

Sprague Dawley rats; males

90

a-tDCS

Right sensorimotor cortex

0.25

0.071

20

N/A

Right anterior chest

0.5

N

Y (7 days)

# BDNF, CREB, synapsin, and CaMKII mRNA expression levels (ipsilateral cortex) and c-fos (hippocampus)

Stafford et al. [73]

2018

NDM

Sprague Dawley rats, males

16

a-tDCS

Caudal to bregma

0.25

0.25

30

N/A

Ventral thorax

N/A

N

N (single session)

↑ AMPAR translocation to the synapse in the hippocampus and ↑ phosphorylation of the S831 site on GluA1

Martins et al. [97]

2019

NDM

Male Wistar rats; males

50

a-tDCS

Left mPFC

0.4

N/A

13

N/A

N/A

N/A

N/A

Y (5 days)

↑ Spatial working memory

↑ GAP-43 (extinct by AMPAR antagonist PRP)

Yu et al. [41]

2019

NDM

Sprague Dawley rats; males

224

a-tDCS

SC dorsal to the hippocampus

0.25

0.25

30

N/A

Anterior chest

N/A (EEG electrode)

Y

N (single session)

↑ Memory (passive avoidance memory retention)

↑ LTP in CA1 hippocampus (blocked by TrkB antagonist); ↑BDNF in CA1 hippocampus

Abbreviations: rtDCS: repetitive transcranial direct current stimulation; a-tDCS: anodal transcranial direct current stimulation; c-tDCS: cathodal transcranial direct current stimulation; C57BL/6: mouse strain; SC: stereotaxic coordinates; NDM: no disease model; SHR: spontaneous hypertensive rats; WKY: Wistar Kyoto rats; PFC: prefrontal cortex; mPFC: medial prefrontal cortex; dPFC: dorsolateral prefrontal cortex; DG: dentate gyrus; STR: striatum; S1: somatosensory cortex; V1: primary visual cortex; ITC: inferotemporal cortex; CA1: cornu ammonis 1 region in the hippocampus; TBI: traumatic brain injury; PRP: perampanel; CREB: cAMP response element-binding protein (transcription factor); CREB/CBP: cAMP response element binding protein; BDNF: brain-derived neurotrophic factor; DA: dopamine; GAP-43: growth associate protein 43; CaMKII: Ca²⁺/calmodulin-dependent protein kinase; mRNA: messenger ribonucleic acid; IP3R2: inositol triphosphate type 2 receptor; A1AR: adenosine A2A receptor; AMPAR: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; GluA1: AMPA receptor subunit A1; LFP: local field potential; LTP: long-term potentiation; PPF: paired pulse facilitation; EEG: eletroencephalography; A/m²: ampere per square meter; mA: milliampere; cm²: square centimeter; mm: millimeter; h: hour; min: minute; vs.: versus; Y: yes; N: no; N/A: not available.