Using Optogenetics to Dissect the Neural Circuits Underlying OCD and Related Disorders

• Published in: Current treatment options in psychiatry Vol. 2; no. 3; pp. 297 - 311
• Main Authors: Piantadosi, Sean C., Ahmari, Susanne E.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2015; Springer Nature B.V
• Subjects: Anxiety; Anxiety disorders; Behavior; Brain; Habits; Hyperactivity; Hypotheses; Medical imaging; Medicine; Medicine & Public Health; Neuroimaging; Neurology; Obsessive Compulsive and Related Disorders; Obsessive Compulsive and Related Disorders (B Brennan and D Dougherty; Obsessive compulsive disorder; Pathophysiology; Psychiatry; Section Editors; Topical Collection on Anxiety; Dorsolateral striatum; OCD; Orbitofrontal cortex; Grooming; Goal-directed behavior; Habitual behavior; Optogenetics; Corticostriatal; Ventromedial striatum; Dorsomedial striatum
• ISSN: 2196-3061; 2196-3061
• DOI: 10.1007/s40501-015-0056-3

Opinion Statement Clinical and preclinical studies have uncovered substantial evidence that dysfunction in cortico-striatal-thalamo-cortical (CSTC) loops central to the selection of action strategies may underlie obsessive compulsive disorder (OCD) symptoms. In human OCD, data suggest that the balance between selections of habitual versus goal-directed action strategies is disrupted, with concomitant hyperactivation of CSTC regions associated with these strategies. Preclinical lesion and inactivation studies of homologous CSTC regions in rodents have shed light on how sub-regions of the frontal cortex and striatum can have dissociable effects on the exhibition of goal-directed or habitual behavior. However, these traditional methods lack the precision necessary to dissect the exact projections and cell types underlying these behaviors. It is essential to uncover this information to begin to determine how disruption in these circuits may lead to disease pathology. Here, we summarize several recent studies that utilize optogenetics, a technique that allows stimulation or inhibition of specific neural projections and cell types using light, to further understand the contribution of CSTC activity to both action selection and the OCD-relevant behavior of perseverative grooming. Based on these experiments and findings in human OCD patients, we argue that OCD symptoms may not only be associated with an enhancement of habitual behavior, but also with aberrant recruitment of goal-directed neural circuits. We also discuss the current status of translating optogenetic technology to primates, as well as how findings in rodents may help inform treatment of patients suffering from OCD and related disorders.