Abstract
Signal transduction upon activation of receptor tyrosine kinases by neurotrophins and nuclear receptors by glucocorticoids is essential for homeostasis. Phosphorylation (PO4) is one way these receptors communicate with one another to support homeostatic reactions in learning and memory. Using a newly developed glucocorticoid receptor (GR)-PO4–deficient knock-in mouse, we show that consolidation of learning-induced neuroplasticity depends on both GR-PO4 and neurotrophic signaling. Cross-talk between these pathways affects experience-dependent neuroplasticity and behavior, extending previous implications of neurotrophic priming of glucocorticoid response for adaptive plasticity to chronic stress and antidepressant response. Therefore, a disruption of cross-talk between these pathways by, for example, the misalignment of circadian glucocorticoid release and experience-dependent neurotrophic signaling may contribute to the pathophysiology of stress-related disorders.