TY - JOUR
T1 - Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice
AU - Hadjas, Lotfi C.
AU - Schartner, Michael M.
AU - Cand, Jennifer
AU - Creed, Meaghan C.
AU - Pascoli, Vincent
AU - Lüscher, Christian
AU - Simmler, Linda D.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Obsessive-compulsive disorder (OCD) is a circuit disorder involving corticostriatal projections, which play a role in motor control. The Sapap3-knockout (KO) mouse is a mouse model to study OCD and recapitulates OCD-like compulsion through excessive grooming behavior, with skin lesions appearing at advanced age. Deficits in corticostriatal control provide a link to the pathophysiology of OCD. However, there remain significant gaps in the characterization of the Sapap3-KO mouse, with respect to age, specificity of synaptic dysfunction, and locomotor phenotype. We therefore investigated the corticostriatal synaptic phenotype of Sapap3-KO mice using patch–clamp slice electrophysiology, in adult mice and with projection specificity. We also analyzed grooming across age and locomotor phenotype with a novel, unsupervised machine learning technique (MoSeq). Increased grooming in Sapap3-KO mice without skin lesions was age independent. Synaptic deficits persisted in adulthood and involved the projections from the motor cortices and cingulate cortex to the dorsolateral and dorsomedial striatum. Decreased synaptic strength was evident at the input from the primary motor cortex by reduction in AMPA receptor function. Hypolocomotion, i.e., slowness of movement, was consistently observed in Sapap3-KO mice. Our findings emphasize the utility of young adult Sapap3-KO mice to investigate corticostriatal synaptic dysfunction in motor control.
AB - Obsessive-compulsive disorder (OCD) is a circuit disorder involving corticostriatal projections, which play a role in motor control. The Sapap3-knockout (KO) mouse is a mouse model to study OCD and recapitulates OCD-like compulsion through excessive grooming behavior, with skin lesions appearing at advanced age. Deficits in corticostriatal control provide a link to the pathophysiology of OCD. However, there remain significant gaps in the characterization of the Sapap3-KO mouse, with respect to age, specificity of synaptic dysfunction, and locomotor phenotype. We therefore investigated the corticostriatal synaptic phenotype of Sapap3-KO mice using patch–clamp slice electrophysiology, in adult mice and with projection specificity. We also analyzed grooming across age and locomotor phenotype with a novel, unsupervised machine learning technique (MoSeq). Increased grooming in Sapap3-KO mice without skin lesions was age independent. Synaptic deficits persisted in adulthood and involved the projections from the motor cortices and cingulate cortex to the dorsolateral and dorsomedial striatum. Decreased synaptic strength was evident at the input from the primary motor cortex by reduction in AMPA receptor function. Hypolocomotion, i.e., slowness of movement, was consistently observed in Sapap3-KO mice. Our findings emphasize the utility of young adult Sapap3-KO mice to investigate corticostriatal synaptic dysfunction in motor control.
UR - http://www.scopus.com/inward/record.url?scp=85087069870&partnerID=8YFLogxK
U2 - 10.1038/s41386-020-0747-3
DO - 10.1038/s41386-020-0747-3
M3 - Article
C2 - 32585679
AN - SCOPUS:85087069870
SN - 0893-133X
VL - 45
SP - 2020
EP - 2029
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 12
ER -