Venue : BBS amphithéâtre
Team : Neurophysiology of Repetitive Behaviours
Paris Brain Institute
Invited by Shauna Parkes (INCIA)
How to model obsessive-compulsive disorder in a mouse? A critical view. From closed-loop optogenetic stimulation to cognitive endophenotyping
Dysregulations in fronto-striatal circuitry, in particular the orbitofrontal cortex and the associative striatum, seem to be implicated in obsessive-compulsive disorder (OCD). Neurobiologically validated mouse models of compulsive-like behaviours, including the Sapap3-KO mouse that we focus on in our laboratory, share these characteristics and allow for the identification of underlying neural substrates. However, incorrect labeling of behavioural phenotypes, inadequate focusing on a single psychiatric symptom, and missing to assess inherent heterogeneity or comorbidity could mislead the identification of underlying neural substrates and corresponding appropriate treatments.
The first part of my talk will focus on the role of striatal parvalbumin-positive interneurons in the regulation of striatal activity and the generation of compulsive-like behaviours in the Sapap3-KO mouse model. I will present our recent study, where we use closed-loop optogenetic stimulation of striatal parvalbumin-positive interneurons to decrease exaggerated, compulsive-like self-grooming to regular wildtype levels. Notably, in such approach, we take advantage of a low-frequency electrophysiological biomarker (2-4Hz) in order to predict self-grooming onset.
In the second part of my talk, I’ll discuss the opportunities and limits of focusing on a particular phenotype in the context of such a complex neuropsychiatric condition as OCD. I’ll share our insights on comorbidity and heterogeneity as well as preliminary data on cognitive endophenotyping using our novel automated operant phenotyping setup.