Transcranial Electrical Brain Stimulation in Alert Rodents

Summary

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

Abstract

Transcranial electrical brain stimulation can modulate cortical excitability and plasticity in humans and rodents. The most common form of stimulation in humans is transcranial direct current stimulation (tDCS). Less frequently, transcranial alternating current stimulation (tACS) or transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range, is used. The increase of noninvasive electrical brain stimulation research in humans, both for experimental and clinical purposes, has yielded an increased need for basic, mechanistic, safety studies in animals. This article describes a model for transcranial electrical brain stimulation (tES) through the intact skull targeting the motor system in alert rodents. The protocol provides step-by-step instructions for the surgical set-up of a permanent epicranial electrode socket combined with an implanted counter electrode on the chest. By placing a stimulation electrode into the epicranial socket, different electrical stimulation types, comparable to tDCS, tACS, and tRNS in humans, can be delivered. Moreover, the practical steps for tES in alert rodents are introduced. The applied current density, stimulation duration, and stimulation type may be chosen depending on the experimental needs. The caveats, advantages, and disadvantages of this set-up are discussed, as well as safety and tolerability aspects.

Introduction

The transcranial administration of electrical currents to the brain (tES) has been used for decades to study brain function and to modify behavior. More recently, applying direct currents, or less frequently alternating currents (tACS and tRNS), noninvasively through the intact skull by use of two or more electrodes (anode(s) and cathode(s)) has gained scientific and clinical interest. In particular, tDCS has been used in more than 33,200 sessions in healthy subjects and patients with neuropsychiatric diseases and has emerged as a safe and easy, cost-effective bedside application, with possible therapeutic potential as well as long-lasting behavioral effects

Protocol

For research involving animals, the relevant (country-specific) approvals must be obtained before starting experiments. All animal experiments reported here are performed according to the EU directive 2010/63/EU, the updated German animal protection law ("Tierschutzgesetz") of July 2013, and the updated German animal research regulations of August 2013. Animal protocols have been approved by the local authorities "Commission for Animal Experimentation of the Regional Council of Freiburg" and "Commission for Animal Experimentation of the University Medical Center Freiburg".

1. Preparation of Instrumentation and Material....

Results

The described implementation of a set-up for reliable repeated tES in alert rodents can be easily integrated into mechanistic experiments, dose-response studies, or experiments including behavioral tasks. To date, the comparability of data from animal studies using (noninvasive) tES is hindered by the variability of the tES stimulation set-ups between laboratories and by differences in stimulation parameters (e.g., various current densities applied at exorbitant high levels compa.......

Discussion

This protocol describes typical materials and procedural steps for surgical realization of a permanent tES set-up, as well as for subsequent stimulation in alert rodents. During preparation of a rodent tES experiment, several methodological aspects (safety and tolerability of tES, outcome parameter) as well as conceptual aspects (comparability with human condition, anticipated effects of stimulation on a particular brain region) need to be taken into account. From a methodological point of view, the surgical set-up of th.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Softasept N	B. Braun Melsungen AG, Melsungen, Deutschland	3887138	antiseptic agent
Ethanol 70 %	Carl Roth GmbH & Co. KG, Karlsruhe, Deutschland	T913.1
arched tip forceps	FST Fine science tools, Heidelberg, Deutschland	11071-10
Iris Forceps, 10cm, Straight, Serrated	World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA	15914
Scalpel Handle #3, 13cm	World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA	500236
Standard Scalpel Blade #10	World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA	500239
Zelletten cellulose swabs	Lohmann und Rauscher, Neuwied, Deutschland	13349	5 x 4 cm
Isoflurane	AbbVie Deutschland GmbH & Co	N01AB06
Iris Scissors, 11.5cm, Straight	World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA	501758	small scissors
cotton swab/cotton buds	Carl Roth GmbH & Co. KG, Karlsruhe, Deutschland	EH12.1	Rotilabo
Kelly Hemostatic Forceps, 14cm, Straight	World Precision Instruments, Inc, Sarasota, FL, USA, Inc, Sarasota, FL, USA	501241	surgical clamp
electrode plate (platinum)	custom made	Wissenschaftliche Werkstatt Neurozentrum Uniklinik Freiburg, Deutschland	10x6 mm, 0.15 mm thickness
insulated copper strands (~1 mm diameter)	Reichelt elektronik GmbH & Co. KG, Sande, Germany	LITZE BL	electrode cable
Weller EC 2002 M soldering station	Weller Tools GmbH, Besigheim, Germany	EC2002M1D
Iso-Core EL 0,5 mm	FELDER GMBH Löttechnik, Oberhausen, Deutschland	20970510	lead free solder
MERSILENE Polyester Fiber Suture	Johnson & Johnson Medical GmbH, Ethicon Deutschland, Norderstedt, Germany	R871H	nonabsorbable braided suture, 4-0
Histoacryl	B. Braun Melsungen AG, Melsungen, Deutschland	9381104	cyanoacrylate
Ketamin 10%	Medistar GmbH, Germany	n/a	anesthetics
Rompun 2% (Xylazine)	Bayer GmbH, Germany	n/a	anesthetics