| First Author | Miller OH | Year | 2017 |
| Journal | Cell Rep | Volume | 20 |
| Issue | 8 | Pages | 1867-1880 |
| PubMed ID | 28834750 | Mgi Jnum | J:254933 |
| Mgi Id | MGI:6104128 | Doi | 10.1016/j.celrep.2017.08.002 |
| Citation | Miller OH, et al. (2017) Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior. Cell Rep 20(8):1867-1880 |
| abstractText | The NMDA receptor (NMDAR) antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant depression. Understanding how antagonism of NMDARs alters synapse and circuit function is pivotal to developing circuit-based therapies for depression. Using virally induced gene deletion, ex vivo optogenetic-assisted circuit analysis, and in vivo chemogenetics and fMRI, we assessed the role of NMDARs in the medial prefrontal cortex (mPFC) in controlling depression-related behavior in mice. We demonstrate that post-developmental genetic deletion of the NMDAR subunit GluN2B from pyramidal neurons in the mPFC enhances connectivity between the mPFC and limbic thalamus, but not the ventral hippocampus, and reduces depression-like behavior. Using intersectional chemogenetics, we show that activation of this thalamocortical circuit is sufficient to elicit a decrease in despair-like behavior. Our findings reveal that GluN2B exerts input-specific control of pyramidal neuron innervation and identify a medial dorsal thalamus (MDT)-->mPFC circuit that controls depression-like behavior. |
