Abstract

Pre-clinical deep-brain stimulation (DBS) research has observed a growing interest in the use of portable stimulation devices that can be carried by animals. Not only can such devices overcome many issues inherent with a cable tether, such as twisting or snagging, they can also be utilized in a greater variety of arenas, including enclosed or large mazes. However, these devices are not inherently designed for water-maze environments, and their use has been restricted to individually-housed rats in order to avoid damage from various social activities such as grooming, playing, or fighting. By taking advantage of 3D-printing techniques, this study demonstrates an ultra-small portable stimulator with an environmentally-protective device housing, that is suitable for both social-housing and water-maze environments. The miniature device offers 2 channels of charge-balanced biphasic pulses with a high compliance voltage (12 V), a magnetic switch, and a diverse range of programmable stimulus parameters and pulse modes. The device's capabilities have been verified in both chronic pair-housing and water-maze experiments that asses the effects of nucleus reuniens DBS. Theta-burst stimulation delivered during a reference-memory water-maze task (but not before) had induced performance deficits during both the acquisition and probe trials of a reference memory task. The results highlight a successful application of 3D-printing for expanding on the range of measurement modalities capable in DBS research.

Highlights

  • IntroductionDeep-brain stimulation (DBS) research has traditionally relied on the use of a cable tether, for connecting an awake animal to the stimulating hardware

  • In animal behavioral studies, deep-brain stimulation (DBS) research has traditionally relied on the use of a cable tether, for connecting an awake animal to the stimulating hardware

  • The benefits of group-housing rats include a normalization in many behavioral and physiological effects that would otherwise occur in healthy rats, including weight gain (Levitsky, 1970; Fiala et al, 1977; Pérez et al, 1997; Lopak and Eikelboom, 2000; Pinnell et al, 2016), stress-induced FOS activity (Westenbroek et al, 2003), as well as heart-rate and blood pressure changes (Sharp et al, 2002)

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Summary

Introduction

Deep-brain stimulation (DBS) research has traditionally relied on the use of a cable tether, for connecting an awake animal to the stimulating hardware. 2013), and implantable systems (Millard and Shepherd, 2007; de Haas et al, 2012) While these devices are successful in granting the operator increased flexibility with regards to the experimental design and arena selection, there are behavioral paradigms with which these devices cannot be utilized. The benefits of group-housing rats include a normalization in many behavioral and physiological effects that would otherwise occur in healthy rats, including weight gain (Levitsky, 1970; Fiala et al, 1977; Pérez et al, 1997; Lopak and Eikelboom, 2000; Pinnell et al, 2016), stress-induced FOS activity (Westenbroek et al, 2003), as well as heart-rate and blood pressure changes (Sharp et al, 2002) This becomes important when chronic stimulation paradigms are utilized, which may involve weeks of social isolation (e.g., Forni et al, 2012). Being able to co-house animals during prolonged periods of stimulation, may offer a way to normalize stress-induced behavioral and physiological deficits that may otherwise interfere with the parameters under study

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