Topographical EEG Recordings of Visual Evoked Potentials in Mice using Multichannel Thin-film Electrodes
Summary
The present protocol describes a simple procedure to acquire and analyze the topography of epicranial visual evoked potentials with 32-multichannel thin-film electrodes in the mouse.
Abstract
Visual evoked potentials (VEP) allow the characterization of visual function in preclinical mouse models. Various methods exist to measure VEPs in mice, from non-invasive EEG, subcutaneous single-electrodes, and ECoG to fully invasive intracortical multichannel visual cortex recordings. It can be useful to acquire a global, topographical EEG-level characterization of visual responses previous to local intracortical microelectrode measurements in acute experimental settings. For example, one use case is to assess global cross-modal changes in VEP topography in deafness models before studying its effects on a local intracortical level. Multichannel epicranial EEG is a robust method to acquire such an overview measure of cortical visual activity. Multichannel epicranial EEG provides comparable results through a standardized, consistent approach to, for example, identify cross-modal, pathological, or age-related changes in cortical visual function. The current study presents a method to obtain the topographical distribution of flash-evoked VEPs with a 32-channel thin-film EEG electrode array in anesthetized mice. Combined with analysis in the time and frequency domain, this approach allows fast characterization and screening of the topography and basic visual properties of mouse cortical visual function, which can be combined with various acute experimental settings.
Introduction
Mice are a preclinical model of degenerative processes of vision and ophthalmological diseases1,2,3,4. Visual evoked potentials (VEPs) are commonly used to measure cortical visual function and, for example, to assess visual degeneration in pathological models5,6. The VEP latency, conduction time, amplitude, multifocal characteristics, or spatial acuity of cortical visual evoked potentials provide diagnostic information on the functional integrity of the visual system7,8,9.
In mice, cortical visual evoked potentials can be measured across various spatial scales with methods of different complexity from non-invasive EEG, subdermal needle electrodes, and skull-implanted screws, to fully invasive intracranial approaches with epicortical ECoG, to intracortical electrode recordings10,11,12,13,14,15,16,17. These methods have different strengths and weaknesses. For example, a low number of electrodes only provides limited information on cortical VEP distribution, whereas subcutaneous needle electrodes often fail to ensure consistent recording locations. Moreover, implanted screws or fully invasive methods require damaging, penetrating, or removing of the skull and often provide only local information.
In acute experiments, a first global overview of cortical visual function is often desired, which is eventually followed by further experimental steps and compared to local intracortical recordings. For example, one potential use case is utilized first to investigate the EEG-level effects of visual cross-modal reorganization of deafness or hearing loss on VEP topography and cortical visual activity18,19 before studying the impacts on a local intracortical level.
Multichannel EEG recordings with thin-film multi-electrode arrays can provide a systematized VEP topography from the mouse skull20,21,22,23,24. Such epicranial recordings can have advantages over ECoG recordings by leaving the integrity of the skull intact and avoiding direct manipulation of the cortical surface. In addition, thin-film multi-electrodes provide a standardized electrode configuration, allowing the comparison of visual evoked spatio-temporal brain activity between experiments similar to a standardized EEG system in humans25. A standardized framework also facilitates using common EEG analysis toolboxes (e.g., Fieldtrip, Chronux, EEGLAB, and ERPLAB) to analyze mouse EEG in the time and frequency domain or in terms of connectivity26,27,28,29,30,31.
The present protocol describes a procedure for topographical VEP recordings in mice using a 32-channel thin-film electrode. This can be used as part of acute experiments followed by additional experimental steps, such as intracortical microelectrode recordings from specific brain areas. It is demonstrated here how to reliably record epicranial flash evoked VEPs with 32-channel thin-film electrodes from the mouse. In addition, exemplary analysis of topographical VEP recordings in the time and frequency domain is presented.
Protocol
Representative Results
Discussion
This article describes a method for recording epi-cranial multichannel EEG with thin-film electrodes and how to acquire a consistent topographical representation of visual evoked potentials in the mouse. Here, we exemplarily showed binocular flash stimulation, but this approach can also be applied with other types of visual stimuli (i.e., monocular, spatial gratings, focal visual field) using, for example, a larger display.
A critical step in the protocol is the positioning of the electro…
Disclosures
The authors have nothing to disclose.
Acknowledgements
This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, Cluster of Excellence 2177 "Hearing4all", Project number 390895286).
Materials
| Bepanthen 5% Dexpantheol | Bayer | Ophtamic gel | |
| Cheetah software 5.11 | Neuralnyx | Version 5.11 | Recording software for neurophysiologcal signals |
| Digital Lynx SX | Neuralynx | Digital Lynx 16SX | Recording system |
| ECG differential amplifier | Otoconsult | WDA2 V1.0 | |
| Electric shaver | Aesculap | GT420 | |
| Electrode Holder | TSE Systems | 430005-HE | |
| Examination light | Heine | HL 5000 | Cold light source lamp |
| Heating Pad + Temperature Control system | CWE | TC-1000 Mouse | |
| Histoacryl 0.5 mL | B.Braun | Tissue adhesive | |
| Infrared heat lamp | Sanitas | SIL 06 | |
| Ketamine 10% | WDT | Ketaminhydrochlorid | |
| LED stroboscope | Monarch | Nova Strobe PBL | Visual stimulation |
| Matlab 2021a | The Mathworks | 2021a | Stimulus control and analysis |
| Moria Vessel Clamp | Fine Science Tools | 18320-11 | |
| Mouse EEG electrode | NeuroNexus | H32 (Reticular) | 32-channel EEG electrode. Thickness: 20 μm; length: 8.6 mm; width 6.8 mm. Platinum sites: 500 μm diameter |
| Mouse Frame | custom made | Information available on request | |
| Multifunction I/O device | National Instruments | PCIe-6353 with BNC 2090A | Analog stimulus generation, output, and trigger |
| NaCl 0.9% | B.Braun | Isotonic, sterile, nonpyrogenic | |
| Neuralynx HS36 | Neuralynx | HS-36 | Headstage |
| Neuronexus probe connector | Neuralynx | ADPT-HS36-N2T-32A | Electrode connector |
| Oscilloscope | Tektronix | TDS 2014B | |
| Progent Intensive Cleaner | Menicon | Protein remover and disinfecting solution for rigid gas permeable lenses | |
| Recording PC | HP | HP Z800 | Recording PC |
| Rimadyl (Carprofen) | Zoetis | Carprofen | |
| Silicon Oil M 1000 | Carl Roth | 4045.1 | |
| Silver wire | Science Products | AG-8W | Diameter 203 µm; ECG and reference electrode |
| Sound proof chamber | IAC acoustics | ||
| Stereotactic Micromanipulator | TSE Systems | 430005-M/P | For EEG electrode placement |
| Stimulation PC | Dell | Dell Precision T5810 | Stimulation PC |
| Surgical microscope | Zeiss | Op-Mi Focus | |
| Surgical tape | 3M | 1527-0 | 1.25 cm x 9.1 m |
| Thilo-Tears 3 mg/g | Alcon Pharma GmbH | Ophtamic gel | |
| Vaselin Lichtenstein | Winthrop | White vaselin ointment | |
| Xylazin 2% | Bernburg | Xylazinehydrochlorid | |
| Xylocaine Spray (10 mg/puff) | Aspen | Lidocaine |
References
- Haider, N. B., Ikeda, A., Naggert, J. K., Nishina, P. M. Genetic modifiers of vision and hearing. Human Molecular Genetics. 11 (10), 1195-1206 (2002).
- Joiner, M. A., Lee, A. Voltage-gated Cav1 channels in disorders of vision and hearing. Current Molecular Pharmacology. 8 (2), 143-148 (2015).
- Krebs, M. P., et al. Mouse models of human ocular disease for translational research. PLOS One. 12 (8), 0183837 (2017).
- Won, J., et al. Mouse model resources for vision research. Journal of Ophthalmology. 2011, 1-12 (2011).
- Peachey, N. S., Ball, S. L. Electrophysiological analysis of visual function in mutant mice. Documenta Ophthalmologica. 107 (1), 13-36 (2003).
- Tokashiki, N., et al. Reliable detection of low visual acuity in mice with pattern visually evoked potentials. Scientific Reports. 8 (1), 15948 (2018).
- Creel, D. J. Visually evoked potentials. Handbook of Clinical Neurology. 160, 501-522 (2019).
- Sutter, E. E. Imaging visual function with the multifocal m-sequence technique. Vision Research. 41 (10-11), 1241-1255 (2001).
- Porciatti, V., Pizzorusso, T., Maffei, L. The visual physiology of the wild type mouse determined with pattern VEPs. Vision Research. 39 (18), 3071-3081 (1999).
- Makowiecki, K., Garrett, A., Clark, V., Graham, S. L., Rodger, J. Reliability of VEP recordings using chronically implanted screw electrodes in mice. Translational Vision Science & Technology. 4 (2), 15 (2015).
- Tomiyama, Y., et al. Measurement of Electroretinograms and Visually Evoked Potentials in Awake Moving Mice. PLOS One. 11 (6), 0156927 (2016).
- You, Y., Klistorner, A., Thie, J., Graham, S. L. Improving reproducibility of VEP recording in rats: electrodes, stimulus source and peak analysis. Documenta Ophthalmologica. 123 (2), 109-119 (2011).
- Yeon, C., Kim, D., Kim, K., Chung, E. Visual evoked potential recordings in mice using a dry non-invasive multichannel scalp EEG sensor. Journal of Visualized Experiments. (131), e56927 (2018).
- Liu, S., et al. An optimized procedure to record visual evoked potential in mice. Experimental Eye Research. 218, 109011 (2022).
- Ryu, S. B., et al. Spatially confined responses of mouse visual cortex to intracortical magnetic stimulation from micro-coils. Journal of Neural Engineering. 17 (5), 056036 (2020).
- Słowiński, P., et al. Background EEG connectivity captures the time-course of epileptogenesis in a mouse model of epilepsy. eNeuro. 6 (4), (2019).
- Troncoso, E., Muller, D., Czellar, S., Zoltan Kiss, J. Epicranial sensory evoked potential recordings for repeated assessment of cortical functions in mice. Journal of Neuroscience Methods. 97 (1), 51-58 (2000).
- Land, R., et al. Cross-modal plasticity in higher-order auditory cortex of congenitally deaf cats does not limit auditory responsiveness to cochlear implants. Journal of Neuroscience. 36 (23), 6175-6185 (2016).
- Land, R., Radecke, J. -. O., Kral, A. Congenital deafness reduces, but does not eliminate auditory responsiveness in cat extrastriate visual cortex. Neuroscience. 375, 149-157 (2018).
- Choi, J. H., Koch, K. P., Poppendieck, W., Lee, M., Shin, H. S. High resolution electroencephalography in freely moving mice. Journal of Neurophysiology. 104 (3), 1825-1834 (2010).
- Lee, M., Kim, D., Shin, H. S., Sung, H. G., Choi, J. H. High-density EEG recordings of the freely moving mice using polyimide-based microelectrode. Journal of Visualized Experiments. (47), e2562 (2010).
- Jonak, C. R., Lovelace, J. W., Ethell, I. M., Razak, K. A., Binder, D. K. Reusable multi-electrode array technique for electroencephalography in awake freely moving mice. Frontiers in Integrative Neuroscience. 12, 53 (2018).
- Land, R., Kapche, A., Ebbers, L., Kral, A. 32-channel mouse EEG: Visual evoked potentials. Journal of Neuroscience Methods. 325, 108316 (2019).
- Kim, D., Yeon, C., Kim, K. Development and experimental validation of a dry non-invasive multichannel mouse scalp EEG sensor through visual evoked potential recordings. Sensors. 17 (2), 326 (2017).
- Megevand, P., Quairiaux, C., Lascano, A., Kiss, J., Michel, C. A mouse model for studying large-scale neuronal networks using EEG mapping techniques. Neuroimage. 42 (2), 591 (2008).
- Lee, C., et al. Dipole source localization of mouse electroencephalogram using the Fieldtrip toolbox. PLOS ONE. 8 (11), 79442 (2013).
- Oostenveld, R., Fries, P., Maris, E., Schoffelen, J. M. FieldTrip: Open source software for advanced analysis of MEG, EEG, and invasive electrophysiological data. Computational Intelligence and Neuroscience. 2011, 156869 (2011).
- Bokil, H., Andrews, P., Kulkarni, J. E., Mehta, S., Mitra, P. P. Chronux: A platform for analyzing neural signals. Journal of Neuroscience Methods. 192 (1), 146-151 (2010).
- Delorme, A., Makeig, S. EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. Journal of Neuroscience Methods. 134 (1), 9-21 (2004).
- Lopez-Calderon, J., Luck, S. J. ERPLAB: An open-source toolbox for the analysis of event-related potentials. Frontiers in Human Neuroscience. 8, 213 (2014).
- Bokil, H., Tchernichovsky, O., Mitra, P. P. Dynamic phenotypes: Time series analysis techniques for characterizing neuronal and behavioral dynamics. Neuroinformatics. 4 (1), 119-128 (2006).
- Ho, D., et al. Heart rate and electrocardiography monitoring in mice. Current Protocols in Mouse Biology. 1 (1), 123-139 (2011).
- Hart, C. Y. T., Burnett, J. C., Redfield, M. M. Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice. American Journal of Physiology – Heart and Circulatory Physiology. 281 (5), 1938-1945 (2001).
- Land, R., Kral, A. Temporal acuity is preserved in the auditory midbrain of aged mice. Neurobiology of Aging. 110, 47-60 (2022).
- Widmann, A., Schröger, E., Maess, B. Digital filter design for electrophysiological data – A practical approach. Journal of Neuroscience Methods. 250, 34-46 (2015).
- Widmann, A., Schröger, E. Filter effects and filter artifacts in the analysis of electrophysiological data. Frontiers in psychology. 3, 233 (2012).
- Skrandies, W. Global field power and topographic similarity. Brain Topography. 3 (1), 137-141 (1990).
- Hamburger, H. L., Michelle, M. A. G. Global Field Power measurement versus classical method in the determination of the latency of evoked potential components. Brain Topography. 3 (3), 391-396 (1991).
- Land, R., Engler, G., Kral, A., Engel, A. K. Response properties of local field potentials and multiunit activity in the mouse visual cortex. Neuroscience. 254, 141-151 (2013).
- Kappenman, E. S., Luck, S. J. The effects of electrode impedance on data quality and statistical significance in ERP recordings. Psychophysiology. 47 (5), 888-904 (2010).
- Calderone, L., Grimes, P., Shalev, M. Acute reversible cataract induced by xylazine and by ketamine-xylazine anesthesia in rats and mice. Experimental Eye Research. 42 (4), 331-337 (1986).
- Land, R., Engel, A., Kral, A. Auditory influences in V1 of mice induced by varying anesthesia level. i-Perception. 2 (8), 755 (2011).
- Land, R., Engler, G., Kral, A., Engel, A. K. Auditory evoked bursts in mouse visual cortex during isoflurane anesthesia. PLOS One. 7 (11), 49855 (2012).
- Hudetz, A. G., Imas, O. A. Burst activation of the cerebral cortex by flash stimuli during isoflurane anesthesia in rats. Anesthesiology. 107 (6), 983-991 (2007).
- Imas, O. A., Ropella, K. M., Ward, B. D., Wood, J. D., Hudetz, A. G. Volatile anesthetics enhance flash-induced gamma oscillations in rat visual cortex. Anesthesiology. 102 (5), 937-947 (2005).
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