| First Author | Wang M | Year | 2021 |
| Journal | Neuron | PubMed ID | 33831348 |
| Mgi Jnum | J:303573 | Mgi Id | MGI:6690331 |
| Doi | 10.1016/j.neuron.2021.03.016 | Citation | Wang M, et al. (2021) Oligophrenin-1 moderates behavioral responses to stress by regulating parvalbumin interneuron activity in the medial prefrontal cortex. Neuron |
| abstractText | Ample evidence indicates that individuals with intellectual disability (ID) are at increased risk of developing stress-related behavioral problems and mood disorders, yet a mechanistic explanation for such a link remains largely elusive. Here, we focused on characterizing the syndromic ID gene oligophrenin-1 (OPHN1). We find that Ophn1 deficiency in mice markedly enhances helpless/depressive-like behavior in the face of repeated/uncontrollable stress. Strikingly, Ophn1 deletion exclusively in parvalbumin (PV) interneurons in the prelimbic medial prefrontal cortex (PL-mPFC) is sufficient to induce helplessness. This behavioral phenotype is mediated by a diminished excitatory drive onto Ophn1-deficient PL-mPFC PV interneurons, leading to hyperactivity in this region. Importantly, suppressing neuronal activity or RhoA/Rho-kinase signaling in the PL-mPFC reverses helpless behavior. Our results identify OPHN1 as a critical regulator of adaptive behavioral responses to stress and shed light onto the mechanistic links among OPHN1 genetic deficits, mPFC circuit dysfunction, and abnormalities in stress-related behaviors. |
