Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects
Brendan D. Hare, R. Shinohara, Rong‐jian Liu, Santosh Pothula, R. DiLeone, R. Duman
Nature Communications January 15, 2019 DOI: 10.1038/s41467-018-08168-9 via Semantic Scholar
Summary
AI-generated from the abstractActivating Drd1 dopamine receptor expressing pyramidal cells in the medial prefrontal cortex (mPFC) produces rapid and long-lasting antidepressant and anxiolytic responses in mice, whereas stimulating Drd2 expressing pyramidal cells does not affect anxiety-like or depression-like measures. Disrupting Drd1 activity also blocks the rapid antidepressant effects of ketamine. Stimulation of mPFC Drd1 terminals in the basolateral amygdala recapitulates the antidepressant effects of somatic stimulation. These findings identify specific cellular targets in the mPFC and downstream circuitry involved in rapid antidepressant responses.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Keywords | Medicine |
| Key finding | Activating Drd1 expressing pyramidal neurons in the mPFC produces rapid and long-lasting antidepressant and anxiolytic responses, and disruption of Drd1 activity blocks the rapid antidepressant effects of ketamine. |
Abstract
Impaired function in the medial prefrontal cortex (mPFC) contributes to depression, and the therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated by mPFC activity. The mPFC contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates the rapid antidepressant actions of ketamine. Here we tested two major subtypes, Drd1 and Drd2 dopamine receptor expressing pyramidal neurons and found that activating Drd1 expressing pyramidal cells in the mPFC produces rapid and long-lasting antidepressant and anxiolytic responses. In contrast, photostimulation of Drd2 expressing pyramidal cells was ineffective across anxiety-like and depression-like measures. Disruption of Drd1 activity also blocked the rapid antidepressant effects of ketamine. Finally, we demonstrate that stimulation of mPFC Drd1 terminals in the BLA recapitulates the antidepressant effects of somatic stimulation. These findings aid in understanding the cellular target neurons in the mPFC and the downstream circuitry involved in rapid antidepressant responses.Ketamine exerts fast-acting anti-depressant responses. Here the authors show that dopamine D1 receptor expressing neurons in the medial prefrontal cortex contribute to these antidepressant-like effects in mice.