In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 9 ( 2019-02-26), p. 3799-3804
Kurzfassung:
Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world’s population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLA Glu ) project onto both medial prefrontal cortex glutamate (mPFC Glu ) and GABA (mPFC GABA ) neurons that locally innervate mPFC Glu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLA Glu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA–mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLA Glu →mPFC GABA→Glu circuit that controls the checking symptoms of OCD.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1814292116
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
2019
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12