DISSECTING THE ROLE OF MIDBRAIN CIRCUITS IN COMPULSIVE-LIKE BEHAVIOR IN A SPONTANEOUS RODENT MODEL

Compulsive behaviors are a hallmark of several psychiatric disorders, yet their underlying neural mechanisms remain poorly understood. Current models emphasize cortical and striatal dysfunction, leaving midbrain sensorimotor circuits comparatively unexplored. In this project, we explore the role of the superior colliculus, a region that helps combine sensory information and guide rapid actions, in the emergence of persistent and repetitive behaviors.
We use Peromyscus maniculatus, a rodent species that naturally exhibits a wide range of repetitive behaviors, to pinpoint circuit features that distinguish animals with high versus low compulsive-like tendencies. Freely moving assays in two different arenas have revealed consistent differences in jumping, summersaulting and pattern-running, allowing to reliably group animals into highly stereotyped and control. For instance, high stereotypy individuals showed 25.4 ± 14.1 jumps/min, while controls only showed 6.7 ± 5.7 jumps/min (mean ± SD).
In ongoing experiments, we use a Navon paradigm-inspired task to test for visual perception alterations in high stereotypy animals. Further, high-density electrophysiological recordings in the dorsal midbrain during spontaneous activity and structured visual challenges are used to uncover the circuit elements underlying these behavioral and perceptual alterations. These data will allow mapping of population dynamics tied to repetitive actions and identify changes in how sensory signals are processed.
Overall, this work aims to build an integrative framework for understanding how midbrain circuits shape compulsive behavior. Identifying how sensory processing and motor selection become rigid at the circuit level may ultimately refine current models of compulsivity and highlight new intervention points beyond traditional cortico-striatal pathways.