Long-term Continuous EEG Monitoring in Small Rodent Models of Human Disease Using the Epoch Wireless Transmitter System

Abstract

Many progressive neurologic diseases in humans, such as epilepsy, require pre-clinical animal models that slowly develop the disease in order to test interventions at various stages of the disease process. These animal models are particularly difficult to implement in immature rodents, a classic model organism for laboratory study of these disorders. Recording continuous EEG in young animal models of seizures and other neurological disorders presents a technical challenge due to the small physical size of young rodents and their dependence on the dam prior to weaning. Therefore, there is not only a clear need for improving pre-clinical research that will better identify those therapies suitable for translation to the clinic but also a need for new devices capable of recording continuous EEG in immature rodents. Here, we describe the technology behind and demonstrate the use of a novel miniature telemetry system, specifically engineered for use in immature rats or mice, which is also effective for use in adult animals.

APC conditional knock-out mouse is a model of infantile spasms with elevated neuronal β-catenin levels, neonatal spasms, and chronic seizures

“…To determine whether neonatal APC cKO mice have abnormal brain activity, we performed EEG recordings by implanting pups with miniaturized EEG radio telemetry transponders at P8 (Zayachkivsky A et al 2013; Zayachkivsky A et al 2015). EEG signals were analyzed for the presence of high amplitude EEG spikes, as seen in individuals with IS (Ohtahara S 1984) and other rodent models of IS (Price MG et al 2009; Scantlebury MH et al 2010).…”

“…EEG data was collected in both neonatal (Zayachkivsky A et al 2013; Zayachkivsky A et al 2015) and adult APC cKO and WT littermate mice (Clasadonte J et al 2013). …”

Enhanced setup for wired continuous long-term EEG monitoring in juvenile and adult rats: application for epilepsy and other disorders

“…Muscle leads can be added to this system by using the differential input on the headbox allowing muscle recordings from up to 6 rats (one channel per rat). In addition, our system still has the limitation imposed by tethering, and thus, unlike wireless techniques [21], cannot record from freely moving rats undergoing behavioral testing or from pups caged with their mother (younger than 21 postnatal days). Nevertheless, our simple-to-implement key modifications result in a markedly improved traditional hardwired EEG and provide the necessary quality and amount of data required for the long-term study of seizure chronobiology in juvenile and adult rats [22] at a much lower cost than more advanced wireless systems.…”

Standards for data acquisition and software‐based analysis of in vivo electroencephalography recordings from animals. A TASK1‐WG5 report of the AES/ILAE Translational Task Force of the ILAE

“…Opportunities in this realm include the development of recording systems with improved signal isolation capabilities, enhanced processing power, and advanced filtering algorithms to optimize the extraction of biological signals, even in noisy or suboptimal experimental conditions. For example, new wireless neurotelemetry systems facilitate the acquisition of relatively artifact‐free data, and minimize animal discomfort for long‐term recordings . Similarly, recent advances in the design and fabrication of electrodes have enabled higher resolution, higher density recording, and in some cases have permitted the acquisition of multiple modalities (e.g., MRI, calcium dye imaging) of information simultaneously .…”

“…For example, new wireless neurotelemetry systems 52,53 facilitate the acquisition of relatively artifact-free data, and minimize animal discomfort for long-term recordings. 54 Similarly, recent advances in the design and fabrication of electrodes have enabled higher resolution, higher density recording, and in some cases have permitted the acquisition of multiple modalities (e.g., MRI, calcium dye imaging) of information simultaneously. 55 With these advances, however, come the challenge of developing new methods for processing and visualizing such high-dimensional data.…”