Plasticity of 5-HT 1A receptor-mediated signaling during early postnatal brain development.
The presence of serotonin 1A receptor (5-HT(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(1A)-R plays a crucial role in this time window of brain development. We show that the 5-HT(1A)-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-HT(1A)-R -->Erk1/2 cascade, which causes increased cell division in the dentate gyrus. By contrast, at P15, PKC alpha 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-HT(1A)-R -->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.
Mehta
Mukti
M
Doctoral Program in Biology (CUNY), New York, NY 10314, USA.
Ahmed
Zagloul
Z
Fernando
Suraj Shawn
SS
Cano-Sanchez
Patricia
P
Adayev
Tatyana
T
Ziemnicka
Dorota
D
Wieraszko
Andrzej
A
Banerjee
Probal
P
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development*; D051379:Mice; D009447:Neuroblastoma; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001973:Bromodeoxyuridine