Thursday, March 07, 2019

Control of OCD behavior by amygdala to prefrontal input.

Sun et al. find a brain circuit in mice regulating OCD behavior that in humans might be susceptible to non drug manipulations such as transcranial magnetic stimulation.

Significance
The pathophysiology underlying obsessive-compulsive disorder (OCD) remains unclear, leading to major challenges in the treatment of OCD patients. Here, we defined a projection from the basolateral amygdala glutamate neurons to the medial prefrontal cortex glutamate and GABA neurons and described the putative importance of this circuit in manifesting the checking symptoms of OCD in mice. In addition, the above major findings were further verified in an fMRI mouse study. These findings raise the possibility of developing optimal treatments for OCD that involve the use of nondrug approaches, such as transcranial magnetic stimulation, that target the converging pathways.
Abstract
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 (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu 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 BLAGlu 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 BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.


1 comment:

  1. it's not an easy topic but I liked your approach a lot, many thanks for this interesting article (and all the others on this blog, they are really remarkable!)

    P.

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