Duplex optogenetic stimulation system modulates compulsive behaviors bidirectionally

Abstract

Decisions enable us to consider our actions while adjusting behaviors to a relentlessly changing environment. Since conscious decision making requires our full attention and is therefore expensive, we use a cheaper system for everyday and repetitive tasks that run automatically without conscious evaluations, commonly described as habits. The combination of these two systems is highly adaptive. However, if there is a disruption in these systems’ balance, mental illnesses such as Obsessive-Compulsive Disorders (OCD) or addiction may arise. Now, how does a newly acquired memory or behavior transition to a habit? We know that the striatum’s dorsolateral region (DLS) plays a significant role in sustaining successful behaviors and habits manifestation. Furthermore, it has been shown that the micro-circuitry of the DLS is organized into two functional opposing pathways that consist of the direct pathway striatal spiny projection neurons (dSPNs), which facilitate movement, and the indirect pathway SPNs, which inhibit actions. Already Freud wrote in the letters to his friend Fliess that memory and motive are inseparable, and its recollection would have no force or meaning unless it would be coupled to a motive or emotion. Therefore, we hypothesize that emotional-associated cues would directly prime the DLS through the amygdala to turn newly acquired behaviors into habits. We are adding new supporting insight for this hypothesis by using a duplex optogenetic stimulation system of the amygdala input in the DLS, modulating specific compulsive behaviors bidirectionally. These behavior modulations were accompanied by spine density modulations and intrinsic excitability changes in the SPNs of the DLS. Keywords: Compulsions; Habits; Optogenetics; Neuromodulation; Dorsolateral striatum; Amygdala.