Abstract
Preadolescent development is characterized by a reorganization of connectivity within and between brain regions that coincides with the emergence of complex behaviors. During the preadolescent period, the rodent hippocampus and regions of the frontal cortex are remodelled as the brain strengthens active connections and eliminates others. In the developing and mature brain, changes in the properties of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAr)-mediated synaptic responses contribute to experience-dependent changes in neural organization and function. AMPAr are made up of 4 subunits, of which GluA1 and GluA2 have been shown to play the most prominent role in functional plasticity. In this study, we sought to determine whether levels of these two subunits changed during the course of pre-adolescent development in the hippocampus and anterior cingulate cortex (ACC). To investigate the developmental changes in GluA1 and GluA2 AMPAr subunits, Western blotting and immunohistochemistry were performed on the ACC and hippocampus from P18 - P30 and compared to adult (P50) levels and distribution. Within the hippocampus, protein levels of GluA1 and GluA2 peaked around P26−30 whereby localized staining in the dentate gyrus reflected this pattern. GluA1 and GluA2 levels within the ACC showed little variation during this developmental period. These results indicate that changes in AMPAr subunits within the hippocampus coincide with developmental modifications that underlie the shift from juvenile- to adult-like capabilities. However, changes in AMPAr distribution in the ACC might not mediate changes that reflect preadolescent developmental shifts.
Highlights
During neural development, a high degree of pruning and remodelling is required for the brain to achieve its final, fully functioning adult configuration (Kantor and Kolodkin, 2003)
The hippocampus undergoes developmentally-linked remodeling (P18 – P24; as previously reported) that is associated with changes in the expression of GluA1 and GluA2 levels (P18 – P24; reported currently)
The developmental maturation of the rodent hippocampus during the preadolescent period is reflected in the emergence of spatial/allocentric memory processing (P20 – P24; Holahan et al, 2019) indicating near-simultaneous developmental changes in connectivity, synaptic excitation and memory function
Summary
A high degree of pruning and remodelling is required for the brain to achieve its final, fully functioning adult configuration (Kantor and Kolodkin, 2003). During the preadolescent period (ending approximately at postnatal (P) days 32–39 in rats; Dutta and Sengupta, 2016) neural regions that subserve memory functions, like the hippocampus and frontal cortex, experience developmentally-linked changes in synaptic organization prior to the onset of adulthood. Mossy fibers, which form connections between hippocampal granule cells in the dentate gyrus and CA3 pyramidal cells, extend from the stratum lucidum to the stratum oriens of the CA3 from P18 to P24 where they remain stable into adulthood (Amaral and Dent, 1981; Gaarskjaer, 1985, 1986; Holahan et al, 2006, 2007) This phase of hippocampal modification is hypothesized to underlie a “switch” from juvenile- to adult-like functioning (Holahan et al, 2019)
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