Developmental changes in plasticity, synaptic, glia, and connectivity protein levels in rat medial prefrontal cortex

Abstract

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.

Developmental changes in plasticity, synaptic, glia, and connectivity protein levels in rat basolateral amygdala

“…Because mTOR and MAP2 levels may reflect neuron-specific cytoskeletal changes in dendrites, these data lead us to speculate that developmental regulation of dendritic structures follows distinct developmental kinetics in different brain regions. Also, the increase in the PSD95 level in the BLA followed the same kinetic as that observed in the mPFC (Jia et al 2018): a significant increase between PN17 and PN24 and a plateau between PN24 and adulthood. However, this kinetic differs from those observed previously in the dHC (Travaglia et al 2016a), which exhibited an elevation of PSD95 between PN24 and adulthood ( Fig.…”

“…The increase in GluN2A/GluN2B ratio over development has been well established in other areas of the postnatal rat brain, including the cortices (Sheng et al 1994;Yashiro and Philpot 2008;Paoletti et al 2013), hippocampus (Travaglia et al 2016a), and mPFC (Jia et al 2018). This switch in NMDAR composition occurs throughout the CNS; is evolutionarily conserved from amphibians to mammals, significantly influences the functional properties of the synapses; and occurs during a time window that coincides with synapse maturation, circuit refinement, and acquisition of learning abilities (Sheng et al 1994;Flint et al 1997;Dumas 2005;Paoletti et al 2013).…”

“…Our results revealed also that the GluN2A subunit remains unchanged with age in the BLA and dHC (Travaglia et al 2016b) but increases between PN17 and PN24 in the mPFC. However, in the BLA, as in the mPFC (Jia et al 2018) and dHC (Travaglia et al 2016b), the GluN2A/ GluN2B ratio increases over the course of development, and that this increase is most prominent between PN17 and PN24, during an interval that coincides with synapse maturation, circuit refinement, and acquisition of learning abilities (Dumas 2005;Paoletti et al 2013). This developmental increase in GluN2A/GluN2B suggests that a change in the biophysical properties and signaling of the NMDAR complex takes place over ages.…”

“…Data are expressed as mean percentage ± SEM of adult rat levels. One-way ANOVA followed by Newman-Keuls post-hoc tests: (**) P < 0.01; (***) P < 0.001. development occur in concert with those of the dHC and mPFC (Travaglia et al 2016a;Jia et al 2018). In adulthood, the BLA, mPFC, and dHC are highly interconnected and all critically recruited in the encoding, consolidation and expression of medialtemporal lobe-dependent memories (McGaugh et al 2002;Preston and Eichenbaum 2013;Eichenbaum 2017;Tonegawa et al 2018); thus, it is plausible that the maturation of BLA, mPFC, and dHC follow similar developmental trajectories.…”

“…One obvious question is whether and how the brain systems engaged in learning and memory change their biology over the course of development, particularly during behavioral maturation. In previous studies, we determined that the dorsal hippocampus (dHC) (Travaglia et al 2016a) and the medial prefrontal cortex (mPFC) (Jia et al 2018), two brain regions that play critical roles in the formation of hippocampus-dependent memories, exhibit significant developmental changes in the expression levels of proteins involved in synaptic plasticity, glia, and connectivity. Our assessment of numerous markers of these functions revealed dramatic changes in rat dHC and mPFC between postnatal day 17 (PN17), PN24, and PN80.…”