5-HT₁A-R signaling during early brain development

The presence of serotonin 1A receptor (5-HT₁A-R) in the hippocampus, amygdala, and most regions of the frontal cortex is essential between postnatal day-5-21 (P5-21) for the expression of normal anxiety levels in adult mice. Thus, the 5-HT₁A-R plays a crucial role in this time window of brain development. We show that the 5-HT₁A-R-mediated stimulation of extracellular signal-regulated kinases 1 and 2 (Erk1/2) in the hippocampus undergoes a transition between P6 and P15. At P6, a protein kinase C (PKC) isozyme is required for the 5-HT₁A-R [implies]Erk1/2 cascade, which causes increased cell division in the dentate gyrus. By contrast, at P15, PKCα participates downstream of Erk1/2 to augment synaptic transmission through the Schaffer Collateral pathway but does not cause increased cell division. Our data demonstrate that the 5-HT₁A-R [implies]Erk1/2 cascade uses PKC isozymes differentially, first boosting the cell division to form new hippocampal neurons at P6 and then undergoing a plastic change in mechanism to strengthen synaptic connections in the hippocampus at P15.