Neuropsychiatric Diseases and Basal Ganglia: Underlying Mechanisms

A central hub in the brain, the basal ganglia governs a diverse array of functions including voluntary movement, procedural memory, habit formation, cognition, and emotion. Comprising a complex network of interconnected subcortical nuclei nestled deep within the brain, these structures play a pivotal role in orchestrating neural signals critical for these processes.

Notably, they are implicated in a myriad of disorders including drug addiction, obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), schizophrenia and Parkinson's disease, collectively affecting 174 million Europeans at a staggering cost of 427 billion euros (1). Our research endeavors are dedicated to unraveling the genetic and the circuits underlying these debilitating diseases. Leveraging preclinical models, we meticulously dissect the physiology and dysfunctions of implicated pathways. Through the utilization of transgenic models, gene manipulation techniques, behavioral assays, and cutting-edge methodologies such as optogenetics (a technique that allows genetically targeted populations of neurons to be manipulated by light on a millisecond scale), in vivo calcium imaging, and electrophysiology, we have delineated the contributions of specific genes in addiction, ASD, and motor control, while uncovering novel neuronal populations and their encoding properties. Presently, our pursuits are twofold: firstly, to elucidate a novel mechanism identified in addiction, paving the way for potential therapeutic interventions in a disease that claims more lives than all cancers combined; and secondly, to elucidate the roles of a newfound neuronal cohort within the basal ganglia orchestrating complex behaviors, thereby enhancing our comprehension of the circuitry underpinning aforementioned behaviors and their dysregulation.

(1) Gustavsson, A. et al. (2011) European Neuropsychopharmacology  21, 718-779