3MDR, a microcomputer-controlled visual stimulation device for psychotherapy-like treatments of mice

Abstract

Post-traumatic stress disorder and other mental disorders can be treated by an established psychotherapy called Eye Movement Desensitization and Reprocessing (EMDR). In EMDR, patients are confronted with traumatic memories while they are stimulated with alternating bilateral stimuli (ABS). How ABS affect the brain and whether ABS could be adapted to different patients or mental disorders is unknown. Interestingly, ABS reduced conditioned fear in mice. Yet, an approach to systematically test complex visual stimuli and compare respective differences in emotional processing based on (semi-)automated behavioral analysis is lacking. We developed 3MDR (Model for MultiModal visual stimulation to Desensitize Rodents) - a novel, open-source, low-cost, customizable device that can be integrated in and TTL-controlled by commercial rodent behavioral setups. 3MDR allows to design and precisely steer multimodal visual stimuli in the head direction of freely-moving mice. Optimized videography allows to semi-automatically analyze rodent behavior during visual stimulation. Detailed building, integration, and treatment instructions along with open-source software provide easy access for inexperienced users. Using 3MDR, we confirmed that EMDR-like ABS persistently improve fear extinction in mice and showed for the first time that ABS-mediated anxiolytic effects strongly depend on physical stimulus properties such as ABS brightness. 3MDR not only enables researchers to interfere with mouse behavior in an EMDR-like setting, but demonstrates that visual stimuli can be used as a noninvasive brain stimulation to differentially alter emotional processing in mice. SIGNIFICANCE STATEMENTAlternating bilateral stimuli (ABS) reduce fear in post-traumatic stress disorder patients and in mice. The mechanism of how classic ABS - typically used in Eye Movement Desensitization and Reprocessing (EMDR) - reduce fear is enigmatic. We provide detailed resources to build a cost-effective, computer-controlled device called 3MDR to perform and semi-automatically analyze EMDR-like treatments in freely-moving mice and to test behavioral effects of multiple ABS variants. Using the 3MDR device, this study confirmed that classic ABS strongly and persistently improve the extinction of conditioned fear in mice - an effect that depended on the brightness of ABS. This novel method may ultimately contribute to a deeper translational and neurobiological understanding of how visual stimuli affect emotional processing in mice.