Plasticity of 5-HT sub(1A) receptor-mediated signaling during early postnatal brain development

The presence of serotonin 1A receptor (5-HT sub(1A)-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-HT sub(1A)-R plays a crucial role in this time window of brain development. We show that the 5-HT sub(1A)-R-mediated stimulation of extracellular signal-regulated kinases 1 and 2 (Erk12) in the hippocampus undergoes a transition between P6 and P15. At P6, a protein kinase C (PKC) isozyme is required for the 5-HT sub(1A)-R [rArr]Erk12 cascade, which causes increased cell division in the dentate gyrus. By contrast, at P15, PKC alpha participates downstream of Erk12 to augment synaptic transmission through the Schaffer Collateral pathway but does not cause increased cell division. Our data demonstrate that the 5-HT sub(1A)-R [rArr]Erk12 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.