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Summary

Abstract

Introduction

Protocol

Representative Results

Discussion

Acknowledgements

Materials

References

Neuroscience

Transcranial Direct Current Stimulation (tDCS) in Mice

Published: September 23rd, 2018

DOI:

10.3791/58517

1Centro de Tecnologia em Medicina Molecular (CTMM), Faculdade de Medicina, Universidade Federal de Minas Gerais

Transcranial direct current stimulation (tDCS) is a therapeutic technique proposed to treat psychiatric diseases. An animal model is essential for understanding the specific biological alterations evoked by tDCS. This protocol describes a tDCS mouse model that uses a chronically implanted electrode.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique proposed as an alternative or complementary treatment for several neuropsychiatric diseases. The biological effects of tDCS are not fully understood, which is in part explained due to the difficulty in obtaining human brain tissue. This protocol describes a tDCS mouse model that uses a chronically implanted electrode allowing the study of the long-lasting biological effects of tDCS. In this experimental model, tDCS changes the cortical gene expression and offers a prominent contribution to the understanding of the rationale for its therapeutic use.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, therapeutic technique, which focuses on neuronal modulation through the use of low-intensity continuous currents1. There are currently two setups (anodal and cathodal) for tDCS. While the anodal stimulation exerts a current electric field too weak to trigger action potentials, electrophysiology studies have shown that this method produces changes in synaptic plasticity2. For example, evidence shows that tDCS induces long-term potentiation (LTP) effects such as increased peak amplitude of the excitatory postsynaptic potentials3

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Individually-housed male adult (8-12 weeks) C57BL/6 mice were used in this experiment. Animals received proper care before, during and after experimental procedures with food and water ad libitum. All procedures were approved by the animal ethics committee from Federal University of Minas Gerais (protocol number 59/2014).

1. Electrode Placement

  1. Sedating and fixating the animal onto the stereotaxic apparatus
    1. Sterilize all the necessary .......

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The surgical protocol presented long-term implant stability for at least one month, with no inflammatory signals at the stimulated site nor any other undesired effect. All the animals survived the surgical procedure and tDCS sessions (n = 8). In this experiment, tDCS implants were positioned over the M1 and M2 cortices (+1.0 mm anterior-posterior and 0.0 mm lateral to bregma). One week later, tDCS (n = 3-4) and sham (n = 3) mice were stimulated for five consecutive days during 10 min at 0.......

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In recent years, neurostimulation techniques have been entering clinical practice as a promising procedure to treat neuropsychiatric disorders23. To reduce the constraint imposed by the lack of knowledge of the mechanisms of neurostimulation, we presented here a tDCS mouse model carrying an electrode that can target brain regions. Since the electrode is chronically implantable, this animal model enables the investigation of long-lasting biological effects evoked by tDCS (for at least 1 month) in c.......

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We thank Mr. Rodrigo de Souza for assistance in maintaining mouse colonies. L.A.V.M is a CAPES postdoctoral fellow. This work was supported by the grant PRONEX (FAPEMIG: APQ-00476-14).

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Name Company Catalog Number Comments
BD Ultra-Fine 50U Syringe BD 10033430026 For intraperitonially injection.
Shaver (Philips Multigroom) Philips (Brazil) QG3340/16 For surgical site trimming.
Surgical Equipment
Model 940 Small Animal Stereotaxic Instrument with Digital Display Console KOPF 940 For animal surgical restriction and positioning.
Model 922 Non-Rupture 60 Degree Tip Ear Bars KOPF 922 For animal surgical restriction and positioning.
Cannula Holder KOPF 1766-AP For implant positioning.
Precision Stereo Zoom Binocular Microscope (III) on Boom Stand WPI PZMIII-BS For bregma localization and implant positioning.
Temperature Control System Model  KOPF TCAT-2LV For animal thermal control.
Cold Light Source  WPI WA-12633 For focal brightness
Tabletop Laboratory Animal Anesthesia System with Scavenging VetEquip 901820 For isoflurane delivery and safety.
VaporGuard Activated Charcoal Adsorption Filter VetEquip 931401 Delivery system safety measures. 
Model 923-B Mouse Gas Anesthesia Head Holder KOPF 923-B For animal restriction and O2 and isoflurane delivery.
Oxygen regulator, E-cylinder  VetEquip 901305 For O2 regulation and delivery.
Oxygen hose – green  VetEquip 931503 For O2 and isoflurane delivery.
Infrared Sterilizer 800 ºC Marconi MA1201 For instrument sterilization.
Surgical Instruments
Fine Scissors - ToughCut Fine Science Tools 14058-11 For incision.
Surgical Hooks INJEX 1636 In House Fabricated - Used to clear the surgical site from skin and fur.
Standard Tweezers or Forceps - - For skin grasping.
Surgical Consumables
Vetbond 3M SC-361931 For incision closing.
Cement and Catalyzer KIT (Duralay) Reliance 2OZ For implant fixation.
Sterile Cotton Swabs (Autoclaved) JnJ 75U For surgical site antisepsis. 
24 Well Plate (Tissue Culture Plate) SARSTEDT 831,836 For cement preparation.
Application Brush parkell S286 For cement mixing and application.
Pharmaceutics
Xylazin (ANASEDAN 2%) Ceva Pharmaceutical (Brazil) P10160 For anesthesia induction.
Ketamine (DOPALEN 10%) Ceva Pharmaceutical (Brazil) P30101 For anesthesia induction.
Isoflurane (100%) Cristália (Brazil) 100ML For anesthesia maintenance.
Lidocaine (XYLESTESIN 5%) Cristal Pharma - For post-surgical care.
Ketoprofen (PROFENID 100 mg) Sanofi Aventis 20ML For post-surgical care.
Ringer's Lactate Solution SANOBIOL LAB ############ For post-surgical care.
TobraDex (Dexamethasone 1 mg/g) Alcon 631 For eye lubrification and protection. 
Stimulation
Animal Transcranial Stimulator Soterix Medical 2100 For current generation.
Pin-type electrode Holder (Cylindrical Holder Base) Soterix Medical 2100 Electrode support (Implant).
Pin-type electrode (Ag/AgCl) Soterix Medical 2100 For current delivery (electrode). 
Pin-type electrode cap Soterix Medical 2100 For implant protection.
Body Electrode (Ag/AgCl Coated) Soterix Medical 2100 For current delivery (electrode). 
Saline Solution (0.9%) FarmaX ############ Conducting medium for current delivery.
Standard Tweezers or Forceps - - For tDCS setup.
Real Time Polymerase Chain Reaction
BioRad CFX96 Real Time System BioRad C1000 For qPCR
SsoAdvancedTM Universal SYBR Green Supermix (5 X 1mL) BioRad 1725271 For qPCR
Hard Shell PCR Plates PCT COM 50 p/ CFX96 BioRad HSP9601 For qPCR
Microseal "B" seal pct c/ 100 BioRad MSB1001 For qPCR

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