The medial prefrontal cortex (mPFC) plays a critical role in complex brain functions including decision-making, integration of emotional, and cognitive aspects in memory processing and memory consolidation. Because relatively little is known about the molecular mechanisms underlying its development, we quantified rat mPFC basal expression levels of sets of plasticity, synaptic, glia, and connectivity proteins at different developmental ages. Specifically, we compared the mPFC of rats at postnatal day 17 (PN17), when they are still unable to express long-term contextual and spatial memories, to rat mPFC at PN24, when they have acquired the ability of long-term memory expression and finally to the mPFC of adult rats. We found that, with increased age, there are remarkable and significant decreases in markers of cell activation and significant increases in proteins that mark synaptogenesis and synapse maturation. Furthermore, we found significant changes in structural markers over the ages, suggesting that structural connectivity of the mPFC increases over time. Finally, the substantial biological difference in mPFC at different ages suggest caution in extrapolating conclusions from brain plasticity studies conducted at different developmental stages.

The basolateral complex of amygdala (BLA) processes emotionally arousing aversive and rewarding experiences. The BLA is critical for acquisition and storage of threat-based memories and the modulation of the consolidation of arousing explicit memories, that is, the memories that are encoded and stored by the medial temporal lobe. In addition, in conjunction with the medial prefrontal cortex (mPFC), the BLA plays an important role in fear memory extinction. The BLA develops relatively early in life, but little is known about the molecular changes that accompany its development. Here, we quantified relative basal expression levels of sets of plasticity, synaptic, glia, and connectivity proteins in the rat BLA at various developmental ages: postnatal day 17 (PN17, infants), PN24 (juveniles), and PN80 (young adults). We found that the levels of activation markers of brain plasticity, including phosphorylation of CREB at Ser133, CamKIIα at Thr286, pERK1/pERK2 at Thr202/Tyr204, and GluA1 at Ser831 and Ser845, were significantly higher in infant and juvenile compared with adult brain. In contrast, age increase was accompanied by a significant augmentation in the levels of proteins that mark synaptogenesis and synapse maturation, such as synaptophysin, PSD95, SynCAM, GAD65, GAD67, and GluN2A/GluN2B ratio. Finally, we observed significant age-associated changes in structural markers, including MAP2, MBP, and MAG, suggesting that the structural connectivity of the BLA increases over time. The biological differences in the BLA between developmental ages compared with adulthood suggest the need for caution in extrapolating conclusions based on BLA-related brain plasticity and behavioral studies conducted at different developmental stages.