| First Author | Shin S | Year | 2018 |
| Journal | Neuron | Volume | 97 |
| Issue | 1 | Pages | 195-208.e6 |
| PubMed ID | 29276054 | Mgi Jnum | J:255321 |
| Mgi Id | MGI:6114208 | Doi | 10.1016/j.neuron.2017.11.040 |
| Citation | Shin S, et al. (2018) Drd3 Signaling in the Lateral Septum Mediates Early Life Stress-Induced Social Dysfunction. Neuron 97(1):195-208.e6 |
| abstractText | Early life stress (ELS) in the form of child abuse/neglect is associated with an increased risk of developing social dysfunction in adulthood. Little is known, however, about the neural substrates or the neuromodulatory signaling that govern ELS-induced social dysfunction. Here, we show that ELS-induced downregulation of dopamine receptor 3 (Drd3) signaling and its corresponding effects on neural activity in the lateral septum (LS) are both necessary and sufficient to cause social abnormalities in adulthood. Using in vivo Ca(2+) imaging, we found that Drd3-expressing-LS (Drd3(LS)) neurons in animals exposed to ELS show blunted activity in response to social stimuli. In addition, optogenetic activation of Drd3(LS) neurons rescues ELS-induced social impairments. Furthermore, pharmacological treatment with a Drd3 agonist, which increases Drd3(LS) neuronal activity, normalizes the social dysfunctions of ELS mice. Thus, we identify Drd3 in the LS as a critical mediator and potential therapeutic target for the social abnormalities caused by ELS. |
