Planar cell polarity proteins mediate ketamine-induced restoration of glutamatergic synapses in prefrontal cortical neurons in a mouse model for chronic stress.
Nature communications June 10, 2024 Andiara E Freitas, Bo Feng, Timothy Woo et al. 9 citations
A single low dose of ketamine produces both immediate and lasting antidepressant effects, linked to the repair of glutamatergic synapses in the medial prefrontal cortex. In a mouse model of chronic stress, ketamine altered multiple molecular pathways. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling decreased after chronic corticosterone treatment but increased after ketamine in most excitatory neurons. Similar PCP signaling reductions were predicted in the dorsolateral prefrontal cortex of people with major depressive disorder. Neurons connecting the infralimbic prefrontal cortex to the basolateral amygdala regulated immobility and food intake. Knocking out specific PCP proteins in these neurons blocked ketamine's synapse restoration and behavioral improvements, indicating that PCP proteins in this circuit mediate ketamine's effects.