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Abstract

Introduction

Protocol

Representative Results

Discussion

Acknowledgements

Materials

References

Neuroscience

Non-restraining EEG Radiotelemetry: Epidural and Deep Intracerebral Stereotaxic EEG Electrode Placement

Published: June 25th, 2016

DOI:

10.3791/54216

1Department of Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), 2Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen, DZNE)

Non-restraining EEG radiotelemetry is a valuable methodological approach to record in vivo long-term electroencephalograms from freely moving rodents. This detailed protocol describes stereotaxic epidural and deep intracerebral electrode placement in different brain regions in order to obtain reliable recordings of CNS rhythmicity and CNS related behavioral stages.

Implantable EEG radiotelemetry is of central relevance in the neurological characterization of transgenic mouse models of neuropsychiatric and neurodegenerative diseases as well as epilepsies. This powerful technique does not only provide valuable insights into the underlying pathophysiological mechanisms, i.e., the etiopathogenesis of CNS related diseases, it also facilitates the development of new translational, i.e., therapeutic approaches. Whereas competing techniques that make use of recorder systems used in jackets or tethered systems suffer from their unphysiological restraining to semi-restraining character, radiotelemetric EEG recordings overcome these disadvantages. Technically, implantable EEG radiotelemetry allows for precise and highly sensitive measurement of epidural and deep, intracerebral EEGs under various physiological and pathophysiological conditions. First, we present a detailed protocol of a straight forward, successful, quick and efficient technique for epidural (surface) EEG recordings resulting in high-quality electrocorticograms. Second, we demonstrate how to implant deep, intracerebral EEG electrodes, e.g., in the hippocampus (electrohippocampogram). For both approaches, a computerized 3D stereotaxic electrode implantation system is used. The radiofrequency transmitter itself is implanted into a subcutaneous pouch in both mice and rats. Special attention also has to be paid to pre-, peri- and postoperative treatment of the experimental animals. Preoperative preparation of mice and rats, suitable anesthesia as well as postoperative treatment and pain management are described in detail.

Radiotelemetry is a most valuable methodological approach for measuring a variety of behavioral and physiological parameters in conscious, unrestrained animals of various sizes, particularly in the context of EEG, ECG, EMG, blood pressure, body core temperature or activity measurements 1-7. Theoretically, any species can be analyzed using implantable EEG radiotelemetry from laboratory rodents such as mice and rats to cats, dogs, pigs and primates 3,8. Even fish, reptiles and amphibians are subject to radiotelemetric investigation 9. Over the last two decades, implantable EEG radiotelemetry has proven to be valuable in the characterizat....

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 Ethics Statement: All animal experimentation was performed according to the guidelines of the local and institutional Council on Animal Care (University of Bonn, BfArM, LANUV, Germany). In addition, all animal experimentation was carried out in accordance with superior legislation, e.g., the European Communities Council Directive of 24 November 1986 (86/609/EEC) or individual regional or national legislation. Specific effort is made to minimize the number of animals used and their suffering.

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This section illustrates examples obtained from surface and deep, intracerebral EEG recordings. Initially it should be stated that baseline recordings under physiological conditions are mandatory prior to subsequent recordings following e.g., pharmacological treatment. Such baseline recordings may provide valuable information about functional interdependence of brain rhythmicity with different behavioral states or sleep / circadian rhythmicity. Here, we show examples of recorded .......

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Implantable EEG radiotelemetry is of central relevance as it is a non-restraining technique allowing experimental animals to perform their full repertoire of behavior1,3. This is of major interest as the telemetric approach enables not only spontaneous EEG recordings but also recordings under cognitive tasks and circadian analytical setups, such as T-maze, radial maze, water maze, sleep deprivation tasks or whenever an EEG recording is necessary or helpful during complex cognitive or motor activity.

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The authors would like to thank Dr. Christina Ginkel (German Center for Neurodegenerative Diseases, DZNE), Dr. Michaela Möhring (DZNE) and Dr. Robert Stark (DZNE) for assistance in animal breeding and animal health care. This work was financially supported by the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) Bonn, Germany.

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Name Company Catalog Number Comments
Carprofen (Rimadyl VET - InjektionA2:D43slösung) Pfizer PZN 0110208 20 ml
binocular surgical magnification microscope  Zeiss Stemi 2000 0000001003877, 4355400000000, 0000001063306, 4170530000000, 4170959255000, 4551820000000, 4170959040000, 4170959050000
bulldog serrefine F.S.T. 18051-28 28mm
cages (Macrolon) Techniplast 1264C, 1290D
cold light source Schott KL2500 LCD 9.705 202 ordered at Th.Geyer
cotton tip applicators (sterile) Carl Roth  EH12.1
Dexpanthenole (Bepanthen Wund- und Heilsalbe) Bayer PZN: 1578818
drapes (sterile) Hartmann PZN 0366787
70% ethanol Carl Roth  9065.5
0.3% / 3% hydrogene peroxide solution Sigma 95321 30% stock solution 
gloves (sterile) Unigloves 1570
dental glas ionomer cement KentDental /NORDENTA 957 321
2% glutaraldehyde solution Sigma G6257
Graefe Forceps-curved, serrated F.S.T. 11052-10
Halsey Micro Needle Holder-Tungsten Carbide F.S.T. 12500-12 12.5 cm
heat-based surgical instrument sterilizer F.S.T. 18000-50
heating pad AEG HK5510 520010 ordered at myToolStore
high-speed dental drill Adeor SI-1708
Iris scissors extra thin  F.S.T. 14058-09 9 cm
Inhalation narcotic system (isoflurane) Harvard Apparatus GmbH 34-1352, 10-1340, 34-0422, 34-1041, 34-0401, 34-1067, 72-3044, 34-0426, 34-0387, 34-0415, 69-0230
Isoflurane Baxter 250 ml PZN 6497131
Ketamine Pfizer PZN 07506004
lactated Ringer’s solution (sterile) Braun L7502
Lexar-Baby Scissors-straight, 10 cm F.S.T. 14078-10 10 cm
Nissl staining solution Armin Baack BAA31712159
non-absorbable suture material 5-0/6-0 (sterile) SABANA (Sabafil) N-63123-45
Covidien (Sofsilk) S1172, S1173
Halsey Needle Holder F.S.T. 12001-13 13 cm
pads (sterile) ReWa Krankenhausbedarf 2003/01
0.9% saline (NaCl, sterile) Braun PZN:8609255
scalpel blades with handle (sterile) propraxis 2029/10
Standard Pattern Forceps F.S.T. 11000-12, 11000-14 12 cm and 14.5 cm length
Steel and tungsten electrodes parylene coated  FHC Inc., USA) UEWLGESEANND
stereotaxic frame Neurostar 51730M ordered at Stoelting
(Stereo Drive-New Motorized Stereotaxic)
tapes (sterile) BSN medical GmbH & Co. KG 626225
TA10ETA-F20  DSI 270-0042-001X Radiofrequency transmitter 3.9 g, 
3.9 g, 1.9 cc, input voltage range ± 2.5 mV,
channel bandwidth (B) 1-200 Hz, 
nominal sampling rate (f) 1000 Hz (f = 5B)
temperature operating range 34-41 °C
warranted battery life 4 months
TL11M2-F20EET  DSI 270-0124-001X Radiofrequency transmitter 
3.9 g, 1.9 cc, input voltage range ± 1.25 mV,
channel bandwidth (B) 1-50 Hz, 
nominal sampling rate (f) 250 Hz (f = 5B)
temperature operating range 34-41 °C
warranted battery life 1.5 months
Tissue Forceps- 1x2 Teeth 12 cm F.S.T. 11021-12 12 cm length
Tungsten carbide iris scissors F.S.T. 14558-11 11.5 cm
Vibroslicer 5000 MZ Electron Microscopy Sciences 5000-005
Xylazine (Rompun) Bayer PZN: 1320422

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