A novel wireless brain stimulation device for long-term use in freely moving mice

Abstract

Deep brain stimulation (DBS) has been used in clinical settings for many years despite a paucity of knowledge related to the anatomical and functional substrates that lead to benefits and/or side-effects in various disease contexts. In order to maximize the potential of this approach in humans, a better understanding of its mechanisms of action is absolutely necessary. However, the existing micro-stimulators available for pre-clinical models, are limited by the lack of relevant small size devices. This absence prevents sustained chronic stimulation and real time monitoring of animals during stimulation, parameters that are critical for comparison to clinical findings. We therefore sought to develop and refine a novel small wireless micro-stimulator as a means by which to study consequent behavioural to molecular changes in experimental animals. Building on previous work from our group, we refined our implantable micro-stimulator prototype, to be easily combined with intravital 2-photon imaging. Using our prototype we were able to replicate the well described clinical benefits on motor impairment in a mouse model of Parkinson’s disease in addition to capturing microglia dynamics live during stimulation. We believe this new device represents a useful tool for performing pre-clinical studies as well as dissecting brain circuitry and function.

Towards chronic deep brain stimulation in freely moving hemiparkinsonian rats: applicability and functionality of a fully implantable stimulation system

“…Its great advantage towards DBSsystems currently used in rodent studies is that it is fully implantable. External or partly implanted stimulation systems require single housing of animals or even specialized cages to minimize the chance of system damage [30,31]. Animals in this study could be housed in groups in standard cages, allowing for natural behaviors such as grooming, playing and other social activities.…”

“…However, most of these studies applied only acute stimulation lasting for minutes to hours in animals that were anaesthetized or restrained by cables to external stimulators [24][25][26][27][28]. Some studies investigated longer-term stimulation using systems that were fixed on the animals' heads or combining implanted and external parts [29][30][31]. In contrast, DBS in patients is applied continuously over years through a fully implanted system.…”

Emerging Materials and Technologies with Applications in Flexible Neural Implants: A Comprehensive Review of Current Issues with Neural Devices

“…[ 39 ] However, externally wired implants frustrate freely moving animals, causing continuous irritation and constraints. [ 40 ]…”

Closed-loop neuromodulation will increase the utility of mouse models in Bioelectronic Medicine

“…No matter how small electronics can be made, one of the major components of an implant which cannot be scaled easily to mouse proportions is the battery. In fact, up to 80% of the volume of clinical implants is taken up by the battery (Amar et al, 2015 ). As energy storage devices, batteries have certain structural and functional components that do not scale well, resulting in significantly lower stored energy per volume as battery sizes are reduced.…”