Abstract

Translational comparison of rodent models of neurological and neuropsychiatric diseases to human electroencephalography (EEG) biomarkers in these conditions will require multisite rodent EEG on the skull surface, rather than local area electrocorticography (ECoG) or multisite local field potential (LFP) recording. We have developed a technique for planar multielectrode array (MEA) implantation on the mouse skull surface, which enables multisite EEG in awake and freely moving mice and reusability of the MEA probes. With this method, we reliably obtain 30-channel low-noise EEG from awake mice. Baseline and stimulus-evoked EEG recordings can be readily obtained and analyzed. For example, we have demonstrated EEG responses to auditory stimuli. Broadband noise elicits reliable 30-channel auditory event-related potentials (ERPs), and chirp stimuli induce phase-locked EEG responses just as in human sound presentation paradigms. This method is unique in achieving chronic implantation of novel MEA technology onto the mouse skull surface for chronic multisite EEG recordings. Furthermore, we demonstrate a reliable method for reusing MEA probes for multiple serial implantations without loss of EEG quality. This skull surface MEA methodology can be used to obtain simultaneous multisite EEG recordings and to test EEG biomarkers in diverse mouse models of human neurological and neuropsychiatric diseases. Reusability of the MEA probes makes it more cost-effective to deploy this system for various studies.

Highlights

  • One primary goal of modern neuroscience is to develop techniques for simultaneous monitoring of large areas of brain in awake and freely moving animals (Nicolelis et al, 1997; Buzsáki, 2004; Miyakawa et al, 2012; Alivisatos et al, 2013; Berényi et al, 2014; Mendoza et al, 2016)

  • We have developed and report a reproducible method for in vivo multielectrode array (MEA) implantation on the surface of the mouse skull which can be used for baseline and stimulus-evoked EEG acquisition and analysis in awake, freely moving mice

  • Interpretation of the EEG recordings obtained via the MEA is aided by careful evaluation of the probe map

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Summary

Introduction

One primary goal of modern neuroscience is to develop techniques for simultaneous monitoring of large areas of brain in awake and freely moving animals (Nicolelis et al, 1997; Buzsáki, 2004; Miyakawa et al, 2012; Alivisatos et al, 2013; Berényi et al, 2014; Mendoza et al, 2016) Such techniques have ranged in scale from monitoring individual neurons and local field potentials (LFPs) with microelectrodes such as “silicon probes” (Berényi et al, 2014) to larger-scale recordings such as grid electrodes for electrocorticography (ECoG) (Ledochowitsch et al, 2015; Milikovsky et al, 2017). While certain electrophysiological abnormalities such as the reduced habituation of N1 amplitude have been reproduced in studies of Fragile X Mental Retardation (Fmr1) gene knockout mice with 2-channel EEG recordings (Lovelace et al, 2016), analysis of the full spectrum of abnormalities seen in human EEG recordings would require multisite EEG measurements in an awake animal model

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