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Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects
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Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects
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Journal Article
Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects
2019
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 14/63
/ 64/110
/ 9/74
/ Animals
/ Antidepressive Agents - pharmacology
/ Basolateral Nuclear Complex - radiation effects
/ Female
/ Humanities and Social Sciences
/ Male
/ Nickel
/ Phenols
/ Prefrontal Cortex - drug effects
/ Prefrontal Cortex - metabolism
/ Receptors, Dopamine D1 - metabolism
/ Receptors, Dopamine D2 - metabolism
/ Science
