Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
Radhika Rawat, Elif Tunc-Ozcan, Tammy L. Mcguire, C. Peng, J. Kessler
Nature Communications May 12, 2022 DOI: 10.1038/s41467-022-30386-5 via Semantic Scholar
Summary
Activation of adult-born immature granule neurons (ABINs) in the mouse hippocampal dentate gyrus is both necessary and sufficient for the rapid antidepressant effects of ketamine. Ketamine activates ABINs in stressed and unstressed mice. Chemogenetic inhibition of ABIN activity blocks ketamine's antidepressant effects, while chemogenetic activation of ABINs mimics both the cellular and behavioral effects of ketamine without changing neuron numbers. These findings identify ABINs as a specific cell population mediating ketamine's antidepressant actions, suggesting that targeting ABINs could preserve therapeutic efficacy while limiting side effects.
Study at a glance
Abstract
Ketamine treatment decreases depressive symptoms within hours, but the mechanisms mediating these rapid antidepressant effects are unclear. Here, we demonstrate that activity of adult-born immature granule neurons (ABINs) in the mouse hippocampal dentate gyrus is both necessary and sufficient for the rapid antidepressant effects of ketamine. Ketamine treatment activates ABINs in parallel with its behavioral effects in both stressed and unstressed mice. Chemogenetic inhibition of ABIN activity blocks the antidepressant effects of ketamine, indicating that this activity is necessary for the behavioral effects. Conversely, chemogenetic activation of ABINs without any change in neuron numbers mimics both the cellular and the behavioral effects of ketamine, indicating that increased activity of ABINs is sufficient for rapid antidepressant effects. These findings thus identify a specific cell population that mediates the antidepressant actions of ketamine, indicating that ABINs can potentially be targeted to limit ketamine’s side effects while preserving its therapeutic efficacy. Rawat et al. demonstrate that activation of adult-born immature hippocampal neurons is necessary and sufficient for the acute antidepressant effects of low-dose ketamine in mice.