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Journal of Neuroscience Methods 168 (2008) 119–126

A novel miniature telemetric system for recordingEEG activity in freely moving rats

Damien Lapray 1, Jurgen Bergeler 1, Erwan Dupont,Oliver Thews, Heiko J. Luhmann ∗

Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, D-55128 Mainz, Germany

Received 20 August 2007; received in revised form 27 September 2007; accepted 28 September 2007

bstract

Telemetric recording systems offer the advantage to monitor physiological parameters in freely moving animals without any restrictions inheir explorative behaviour. We present a novel, inexpensive, portable and reusable telemetric system to record the electroencephalogram (EEG)rom adult freely moving rats under various experimental conditions. Our system consists of an implantable transmitter which communicates at aampling rate of 500 Hz bi-directional with a receiver via radio transmission (in EU: 868.35 MHz; in USA: 916.5 MHz) over a distance of up tom. The switching time between receiving and transmitting signals is 20 �s and the data transmission rate amounts to 115.2 kbps. The receiver

s connected to a laptop via an USB connection and the data are displayed and saved by a software developed by the authors. This system allows

he simultaneous recording and storage of a video signal for direct comparison of the animal’s EEG with its behaviour. EEG recordings coulde obtained over 4–5 weeks and under various experimental conditions (i.e. from rats swimming in water). The current system is optimized forecording electrical activity from the animal’s brain, but can be easily modified to record other physiological parameters.

2007 Elsevier B.V. All rights reserved.

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eywords: Telemetry; Electroencephalogram; Freely moving rat; Wireless phy

. Introduction

Recording physiological parameters from freely movingxperimental animals represents a most valuable approach totudy the animal’s milieu interne (e.g. blood pressure, heart beat,ody temperature, brain activity) under relatively natural condi-ions. However, a direct connection of the animal to the recordingpparatus, e.g. a cable connecting the EEG electrode on the ani-al’s head with the EEG recording amplifier, does not only

estrict the animal in its locomotion and exploratory behaviour,ut may also act as a strong stress factor thereby modifyingarious physiological parameters (Tang et al., 2004). Therefore,ireless, so-called telemetric recording systems which are as

omfortable as possible to the awake experimental animal are inany aspects advantageous and more valuable when compared

o conventional recording devices.

∗ Corresponding author. Tel.: +49 6131 39 26070; fax: +49 6131 39 26071.E-mail address: luhmann@uni-mainz.de (H.J. Luhmann).

1 These authors equally contributed to this work.

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165-0270/$ – see front matter © 2007 Elsevier B.V. All rights reserved.oi:10.1016/j.jneumeth.2007.09.029

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Telemetric recording systems should fulfil a number ofequirements in order to guarantee a long-term and powerfulnalysis of physiological parameters in freely moving animalsnder stress-free conditions: (i) All devices, which have to bemplanted in the animal, should be as small and light as pos-ible in order to minimize or better prevent stress and pain tohe animal. The system should be also fully biostable and bio-ompatible in order to allow telemetric recordings over longeriods as weeks or even months. (ii) The energy consumptionf the implanted components should be as low as possible andt should be possible to control the energy source (usually aattery) from extern by switching the system on and off or byecharging the battery. (iii) The system should allow a telemetricransmission of the recorded signals over at least a few metersn order to allow free exploratory behaviour of the animals in aefined environment, e.g. a conventional open field for rodents.iv) The system should work reliably in water in order to allow

elemetric recordings of physiological parameters from diving orwimming animals, e.g. rats in the Morris water maze (Morris,984). (v) Internal components should be re-useable and thexternal recording system should be as simple as possible to

1 oscience Methods 168 (2008) 119–126

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Fig. 1. Schematic illustration of the main components of the telemetric system.The recording electrodes are implanted on the cortical surface and connected to atransmitter placed in the abdominal cavity of the rat. The transmitter is switchedON/OFF by the receiver. The recorded signal is directly amplified and digitizedby the transmitter, emitted in all directions and detected by the receiver at adistance of up to 3 m. The data are transferred from the receiver to a computervaa

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tmnhtinverting operational amplifier with an amplification of 500 andis dc-decoupled by a 2.2 �F non-polarized capacitor. To avoidresonance effects a small capacitor with a value of 470 pF isconnected in parallel to the resistor in the backward path. The

Table 1Properties of the transmitter unit

Property

Weight 4 g (with batteries and wires)Dimensions 40 mm × 8 mm × 5 mmPower supply 2 × 1.55 V (silveroxide)Carrier frequency 868.35 MHz ISM (Europe) 916.5 MHz ISM (USA)Run mode current 1.6 mAStandby mode current 2 �A

20 D. Lapray et al. / Journal of Neur

inimize the expenses. (vi) All external components of the tele-etric system (e.g. the receiver) should be as small as possible

nd portable to allow experiments outside the conventional lab-ratory settings. (vii) In order to allow maximal flexibility in thexperimental design and in the recording protocols, the prop-rties of the signals sent out from the transplanted transmitterhould be adjustable from outside.

In the present report we describe a novel telemetric record-ng system that fulfils all these requirements. We constructed aystem that allows telemetric recording of the electroencephalo-ram (EEG) from adult freely moving rats under differentxperimental conditions. In its current version the system is opti-ized for recording electrical activity from the animal’s brain,

ut by the utilization of other implantable devices the system cane easily used to record other physiological parameters such aslood pressure, heart beat, body temperature, etc.

Telemetric recordings of the EEG in freely moving mam-als is currently an important issue in neurosciences, becausenumber of different brain rhythms have been described in

he last two decades (for review Buzsaki and Draguhn, 2004;inger, 1999; Steriade, 2005; Uhlhaas and Singer, 2006), but

he physiological function and the behavioural context of theifferent brain rhythms are not completely understood (for com-rehensive review Buzsaki, 2006). The use of radio-telemetryo collect EEG measurements or other neurophysiological datan conscious, unrestrained animals is one valuable approacho address these questions (Guler and Ubeyli, 2002). How-ver, the full implantable systems available so far do notransmit the signal over distances that would allow to com-ine recordings with behavioural test in a larger open fieldMumford and Wetherell, 2001; Obeid et al., 2004; Williamst al., 2006). Here we describe the development of a teleme-ry system totally implantable for a maximum freedom fromnterference by the subject. The behaviour is not affected byhe implantation system. This system is suitable for EEG andlectrocorticogram (ECoG) in freely moving rats. Most impor-ant, the EEG signal is transmitted at a distance of up tom, thus cortical electrical activity and behaviour can be syn-hronously recorded and then directly correlated. In addition,e investigated the question if the normal behaviour of the

ats were affected by the implantation surgery and the trans-itter.

. Materials and methods

.1. Overview

Our system consists of an implantable transmitter whichmplifies and AD-DA converts the recorded signal and com-unicates bidirectional with a receiver via radio transmission

ver a distance of up to 3 m (Fig. 1). The receiver is con-ected to a computer via an USB connection and the data areisplayed and saved by a software developed by the authors

or this purpose. A commercially available CED and Spike2oftware (Cambridge Electronic Design, Cambridge, England)an also be used to display and store the data on the hostomputer.

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ia an USB connection and can be visualized online with our software. Thenimal behaviour is synchronously recorded with a video camera and moviesre stored on-line on the PC.

.2. Implanted system

The implanted part of the telemetric system (Fig. 2A,and Table 1 ) consists of a microcomputer (PIC12F675,

icrochip®), an analogue input amplifier and a transceiver.n operational amplifier is also present to generate the vir-

ual ground potential and a power switch in order to reducehe power dissipation during the standby mode. The system isssembled with two stacked printed circuit board (PCB) con-ected by wires. The power supply is composed by two smallilver-oxide batteries (Renata 399, 9.5 mm × 9.6 mm, 55 mAh),onnected by conductive glue (Chemtronics, USA) and con-ected to the PCB by a holder that is constructed by stainlessteel wires.

The first stage of the analogue input path is an instrumen-al amplifier with an amplification of 10. The input voltage is

easured as a differential signal between the positive and theegative input. The reference potential (virtual Ground VGND)as a level of half of the battery voltage and is connected tohe skull of the animal. The second stage is a standard non-

Life time battery 14 h at 500 Hz sampling rate

he system operates at sampling rates sufficient for physiological recordingsf EEG activity (250–2000 Hz). The light transmitter contains a battery that onverage allows 14 h of recording.

D. Lapray et al. / Journal of Neuroscience Methods 168 (2008) 119–126 121

Fig. 2. Properties and function of the implanted part of the telemetry system. (A) Electronic circuit diagram of the implanted unit. (B) Photograph of the telemetricd just tA t other

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evice. (C) Illustration of the protocol, which starts with initiating pulses to adfter 300 �s the transceiver switches to the reception mode and can also detec

eceived to modify the system’s status. (D) Flowchart of the machine program.

nalogue signal is internally digitized in the microcomputer withresolution of 10 bits and a conversion time of 2 �s. The micro-omputer controls the system status “running” and “standby”,he digitalization and the receiving and transmitting of radio sig-als. It contains a non-volatile EEPROM memory of 128 byteshere the parametric data are stored. The implanted system acts

s a receiver and a transmitter following the protocol illustratedn Fig. 2C.

The hybrid transceiver system (TR1001, RF Monolithics®)s available for European (868.35 MHz) and other ISM-bandrequencies (e.g.: USA 916.5 MHz). This part has a unique rapid

witching time between receiving and transmitting of 20 �s inombination with a transmission data rate of 115.2 kbps. Fig. 2Dhows the flowchart of the machine program. After insertinghe battery the system remains in a standby status with a very

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he automatic-gain-control of the receiver and subsequently transmits the data.r transmitters using the free ISM band. During this period instructions can be

ow power dissipation of less than 2 �A. The implanted systemwakes up” every 2.5 s, switches the receiver ON and scans forn instruction to start. This operation takes less than 10 ms. If noignal is received, the system falls back to standby status. Aftereceiving an ON signal the unit starts to measure and transmithe data until it receives an OFF instruction. The acquisitionate can be pre-selected by software from 250 Hz up to 2 kHz.n order to minimize the size of the system most of the parts areurface Mount Devices with a size of 0402.

Before implantation, electrode wires (0.3 mm stainless steelires with HiFlex nylon coating, Griffin, Schramberg, Ger-

any) with small connectors at their tip are plugged on stainless

teal pins on the transmitter and a small layer of epoxy ispplied on the connectors to protect them. These wires can eas-ly be replaced to reuse the system for new implantations. The

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22 D. Lapray et al. / Journal of Neur

ransmitter is then covered with two layers of a biocompatibleilicone (Elastosil N2010, Wacker Chemie AG, Munich, Ger-any). Between the two layers of silicone and the system one

ayer of water-soluble separating agent (PVA, R&G, Walden-uch, Germany) is first applied in order to facilitate the cleaningf the transmitter after extraction from the animal at the endf the experiments. The shape of the silicone is made as roundnd smooth as possible to avoid discomfort and distress of thenimals.

.3. Control system

The receiving and control system is composed of a per-onal computer and an interface box (Fig. 3A, B) connectedia standard USB. The receiver of the interface is the sames in the implanted units except some modifications to adapthe high frequency power and the modulation depth. Accord-ng to the received data rate the implemented microcontroller

PIC16F876A, Microchip®) is connected by a high speed serialnterface (2.5 mbps) to a special interface chip FT232R (IC1,TDI®) which converts the serial data stream into the com-lex USB protocol. The program is written in machine language

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ce Methods 168 (2008) 119–126

o optimize the usage of memory space and processing speed.ecause the microcontroller has the ability to write to its ownrogram memory the software can be updated by the PC.

.4. PC software

The PC software consists of three independent modules for1) capturing data, (2) replaying/analyzing data, and (3) soft-are servicing of the control system and the implanted devices.

n the capture module the user has to define the parameters ofhe capture session (e.g. sampling rate) and whether parallel tohe EEG data acquisition a video recording will be performed.he user can also define a detailed time schedule describing theoints of time and the duration of each recording session. Afternitialization of the control device the software starts the dataransmission of the implanted system. All data will be sent ascontinuous stream in the predefined sample rate. For quality

ssurance each data block contains a unique identification and

successive numbering so that a loss of single data packages

uring wireless transmission can be identified. The data will beritten to the PC hard disk in a binary format together with a

imestamp. In parallel the received data will be displayed on

rface (A) and photograph of the USB unit (B).

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Tnswwnfaw1998) and three holes were made through the skull with a driller(High Speed Micro Drill, Fine Science Tools inc., Heidelberg,Germany) fixed on the stereotaxic apparatus in order to con-trol the descent and avoid any brain damage or bleeding. The

Fig. 4. Implantation procedure. (A) Placement of the transmitter in the abdomi-

D. Lapray et al. / Journal of Neur

he PC screen in scope-like fashion. In the case that a videoamera is attached to the PC via an USB port the software isapable to capture a video stream synchronously to the EEGata recording on the PC hard disk. Due to the large number ofata in this mode the rate of the real-time EEG data display onhe scope is reduced. However, due to extensive buffering a lossf data can be ruled out. Terminating the capture session cane initiated either manually or automatically by the predefinedime schedule. For this reason repetitive recordings over a longeriod of several days without the presence of a human operatorre possible which may be advantageous in the case of long-termehavioural studies.

The replay software module reads the EEG data together withhe stored video stream and displays them synchronously on thecreen. With a time mark the user can indicate time intervals ofnterest. The accompanying EEG data of these time frames canither be stored separately on the hard disk or be exported informat compatible for use with other analysis software (e.g.,pike2, MatLab). In this module the incorporation of individualpecific analysis routines is also possible.

The service module of the software can be used to parame-erize (e.g. setting the sample rate) the implanted devices. Thehole software package is written in Delphi (Cupertino, CA,SA) using modules from the JEDI Visual Component Library

JVCL, http://jvcl.sourceforge.net). Besides the large number ofEG data, video streaming produces extensive file sizes. For this

eason, a suitable size of the hard disk is necessary.

.5. Surgery

All experiments were conducted in accordance with theational and European (86/609/EEC) laws for the use of ani-als in research and were approved by the local ethical

ommittee (Landesuntersuchungsamt Koblenz, 23 177-07/G07--001). Male Wistar rats weighing 250–400 g were used. Thenimals were housed individually in standard plastic cages42 cm × 26 cm × 20 cm) under a 12 h light–dark cycle (lightsn at 7 am). The room temperature was maintained at 21 ± 2 ◦Cnd relative humidity at 50 ± 5%. Standard rodent food and tapater were available ad libitum.The surgery was performed after deeply anaesthetising the

nimals with an intra-peritoneal (IP) injection of chloral hydrate400 mg/kg, chloral hydrate 99%, Sigma–Aldrich, Steinheim,ermany). This was followed after 10 min by the IP injection ofetamine (1 ml/kg, ketamine 500 mg/10 ml, Ratiopharm, Ulm,ermany) and by the subcutaneous (SC) injection of atropine

0.8 mg/kg, Sigma–Aldrich). The anaesthesia was maintainedy ketamine injections during the whole surgery. For a betterecovery all rats were given an antibiotic (IP) (0.1 ml Baytril®

.5 %, Bayer Vital, Leverkusen, Germany) and an analgesicreatment (SC) (0.05 ml Rimadyl®, Pfizer, Karlsruhe, Germany).

The area from the part between the eyes, back between thears and across the neck as well as the abdominal skin were

haved and cleaned with iodine. The animal was then placed onheating pad and an incision was made in the left part of the

bdomen’s mid-line, 1 cm caudal to the xyphoid cartilage, andhe transmitter was placed in the peritoneal cavity (Fig. 4A).

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ce Methods 168 (2008) 119–126 123

he unit could be sutured to the body wall with non-absorbableylon. After secured in the stereotaxic apparatus a 4 cm mid-agittal incision was made on the scalp and the skin reflectedith hemostats to expose the entire skull. A way for the leadsas made between the skin and muscles by moving aside con-ective tissue and transmitter leads were slipped subcutaneouslyrom the abdomen to the incision made on the head (Fig. 4Bnd C). The skull was then cleaned and dried. The Bregmaas marked according to the coordinates (Paxinos and Watson,

al cavity. (B) The leads were slipped under the skin from the belly to the head’sncision and holes were drilled in the skull to place the recording electrodes,hich were fixed to the skull with grip cement. (C) The ground and the refer-

nce electrodes were placed above the cerebellum. In this study, the recordinglectrode was placed above the somatosensory cortex.

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ecording electrode was placed above the somatosensory cortexL = β + 5.5 mm, AP = β − 2.3 mm), the reference and the groundlectrodes were placed above the cerebellum. Three stainless-teal screws (0.5 mm diameter) were used as electrodes andoldered to the leads. The assembling was anchored in placeith grip cement (Dentsply Caulk International, Milford, USA).oth incision sites were closed using 4-0 Resolon (Resorba,urnberg, Germany). Surgery lasted a maximum of 3 h from

nduction of anaesthesia and the success rate was 100% forecovery from anaesthesia and surgery.

The animals were weighed daily throughout the experiments an indicator of general health.

.6. Data recordings

After surgery, a recovery period of 5 days was given to thenimals before starting the first recording session, correspond-ng to the time needed to gain the pre-surgical weight again. Theats were placed in the recording field that could be a cage, anpen field, a labyrinth or a water maze. The recording system waswitched on through the receiver and the signal directly observedn a computer’s screen. The signal was recorded with our soft-are at a sampling rate of 500 Hz and saved on the hard-disk.ata were then imported to MatLab (MatLab 7, The MathWorks

nc., Natick, USA) for further analysis. Frequency analysis waserformed by the use of Fast Fourier Transform (one epoch of00 s) with a band-pass filter between 1 and 80 Hz.

.7. Statistics

Statistical analyses were performed with Systat Version 10Systat Software, Erkrath, Germany). Values throughout this

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ig. 5. Examples of EEG recordings from the somatosensory cortex of adult ratsndividual rats are shown. Lower EEG traces are higher magnifications of the corresuring the EEG recording time. FFT spectra were calculated from 100 s traces. (A) Tleep. (C) Example of EEG recording during treatment with the volatile anaesthetic ind (E) in a two arms maze.

ce Methods 168 (2008) 119–126

eport are given as mean ± S.E.M. For statistical comparisons,n unpaired samples t-test was performed.

. Results

.1. Recovery of the animals after implantation

All the implantations were followed by a lost of weightith a maximum peak 2 days after the surgery (94.6 ± 0.4% ofre-surgery body weight). Five days after the implantation thenimals started again to take weight and reached the surgery’sne after 10 days. No infections or mortality due to the implan-ation were observed on the six rats used for this study. Toest the impact of the system on the animal movements, ratsere placed for 10 min in an empty open field (60 cm × 70 cm)

nd a behavioural recording was made with EthoVision (Noldusnformation Technology, Berlin, Germany). The total distancef moving and the velocity of the animals were then compared toon-implanted rats in the same conditions. No significant differ-nces were observed in these two parameters (30.3 ± 1.7 m and.1 ± 0.3 cm/s for the control animals versus 29.2 ± 1.7 m and.9 ± 0.3 cm/s for the implanted animals, each group n = 6). Theevice did not restrict limb movements during locomotion. Theelemetry device did not cause any discomfort to the animalshich were still able to curl up to sleep, a prominent sleepingosture in rodents (Morton et al., 2003; Tang et al., 2007).

.2. The telemetric system gives recordings that are

omparable with known studies

Animals were recorded during three distinct brain states:akefulness (Fig. 5A), slow-wave sleep (Fig. 5B) and under

under different experimental conditions. Characteristic EEG recordings fromponding upper EEG trace. Each picture is a snapshot from the video recordedhe animals were recorded in their cages during wakefulness and (B) slow-wavesoflurane. (D) Telemetric EEG recordings from animals in an empty open field

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soflurane anaesthesia (Fig. 5C). EEG recordings were mea-ured with a sampling rate of 500 Hz in a normal laboratoryetting with no precautions taken to limit any kind of externallectromagnetic interferences.

Wakefulness was characterized by a desynchronizedow-amplitude EEG with dominant theta activity (4–8 Hz, sup-lementary movie 1). Slow-wave sleep was clearly distinguishedy a synchronized EEG with high-voltage slow-waves in theelta frequency range (1–4 Hz) and some spindles (10–14 Hz)n an immobile animal with closed eyes (supplementary movie). Under isoflurane anaesthesia burst-suppression pattern char-cterized by a depressed background activity alternating withigh voltage activity were observed (supplementary movie 3).ur EEG recordings obtained with the telemetric system are inood agreement with previous reports on EEG activity in sleeptates (Franken et al., 1998; Gervasoni et al., 2000; Timo-Iariat al., 1970) as well as under isoflurane anaesthesia (Hudetz,002).

.3. The telemetric system allows the simultaneousecording of brain activity and animal behaviour

We obtained telemetric recordings from rats in different envi-onmental conditions, like an open field (60 cm diameter, 70 cmeight) (Fig. 5D, supplementary movie 1), in a two arms mazeFig. 5E, supplementary movie 4) and in water (supplemen-ary movie 5). These recordings were performed with a distanceetween the transmitter and the receiver of 0.2–3 m. The signalas devoid of movement artefacts during the recording sessions

xcept for the grooming behaviour where some electrical spikesould be observed especially when the animal was cleaningts belly. These artefacts can be easily identified by the video

onitoring and removed out-line.For the water test we performed recordings of the animals in

n openfield full of water (around 150 l). The signal recordedas devoid of distortions and stable in an area of 30 cm around

he antenna when this one was placed beside the openfield at aevel below the water’s surface.

. Conclusions

We present a novel telemetric recording system that offerseveral advantages compared to the currently available telemet-ic systems. The relatively small size and weight of our fullymplantable device is very well accepted by adult rats whicho not show any kind of behavioural impairments or sign ofiscomfort. The incorporation of an AD-DA converter in theransmitter, the homemade software to display and store theata simultaneously with the video signal on the host com-uter and the possibility to change easily wires and batteryake these system inexpensive, portable and easy to use and

euse, allowing experiments in a wide variety of environments.nother advantage of our system is the transmitting range of

he signal, up to 3 m, without any lost of data which allowsny kind of open field experiments and for EEG recordings inater (e.g. could be used in Morris water maze). Due to this

arge transmitting range and the impossibility to switch ON

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ne system independently, the implanted animal under record-ng session has to be separated from the other implanted ones.xcept this last point no particular precautions have to be taken

n order to limit any kind of external electromagnetic inter-erences allowing recordings directly in the animal facility orny other places. In addition the relatively long lifetime ofhe batteries, due to the low power consumption of the sys-em and possibility to switch on and off by external control,ermits experiments lasting a few weeks. Finally after sac-ificing the implanted animal and extracting the transmitter,he system can be reused several times after changing batter-es and wires. A further miniaturization of the transmitter, thextension of the system to at least two recording channels, aigher transmission and acquisition rate and the addition of ai-directional signal transfer (e.g. for electrical stimulation ofrain regions) will make this system in the future even moreowerful.

cknowledgments

We are grateful to Pascal Ravassard and Dr. Romainoutagny for help with the surgical experiments. We thank Dr.icolas Heck for helpful comments on the manuscript, Hanseiner Polder for technical discussions and Florian Lebayle foris illustrations abilities. DL is member of the neuroscienceraduate school at the University of Mainz (DFG GRK 1044).his work was funded by the Stiftung Rheinland-Pfalz fur Inno-ation and by the EC (LSH-CT-2006-037315, EPICURE).

ppendix A. Supplementary data

Supplementary data associated with this article can beound, in the online version, at doi:10.1016/j.jneumeth.2007.09.29.

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