The developmental stages of synaptic plasticity

Abstract

The brain is programmed to drive behaviour by precisely wiring the appropriate neuronal circuits. Wiring and rewiring of neuronal circuits largely depends on the orchestrated changes in the strengths of synaptic contacts. Here, we review how the rules of synaptic plasticity change during development of the brain, from birth to independence. We focus on the changes that occur at the postsynaptic side of excitatory glutamatergic synapses in the rodent hippocampus and neocortex. First we summarize the current data on the structure of synapses and the developmental expression patterns of the key molecular players of synaptic plasticity, N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as pivotal kinases (Ca(2+)/calmodulin-dependent protein kinase II, protein kinase A, protein kinase C) and phosphatases (PP1, PP2A, PP2B). In the second part we relate these findings to important characteristics of the emerging network. We argue that the concerted and gradual shifts in the usage of plasticity molecules comply with the changing need for (re)wiring neuronal circuits.

Figure 1. Time course of various synaptic components

Time course of the postnatal development of synapses (A) and postsynaptic plasticity molecules (B–E) in the hippocampus, forebrain or whole brain in comparison with cellular, network and behavioural development (F). Curves in A–E are expressed as a percentage of the maximal density or expression level. Original data were smoothed (running average). Original data: A, synapse density (Fiala et al. ; Steward & Falk, 1991). Proportion of filopodia, shaft and spine synapses (P1–P12: Fiala et al. ; P21: Boyer et al. ; adult: Harris et al. 1992). B, GluA1, 2, 2/3, 4 (Zhu et al. 2000); GluA2_long (Kolleker et al. 2003). C, GluN1, 2A, 2B (Sans et al. 2000). D, PKCγ (Roisin & Barbin, 1997); PKA (Kelly, 1982); CaMKII (Kelly & Vernon, 1985). E, PP1β, PP1γ2 (Strack et al. 1999); PP2A, 2B (Takahashi et al. 2000).

Figure 2. Schematic of the structure and plasticity molecules of glutamatergic synapses at four fundamental stages of development

A, between postnatal day 0 and 5 most synapses are located on the dendritic shaft, AMPARs only consist of GluA4 and NMDARs have all GluN2B. Phosphatases PP1 and PP2A are present, but the prime kinases are still absent. B, between postnatal days 5 and 14 synapses are still scarce but start occurring on spines, GluA2_long is temporarily the dominant long-tailed AMPAR subunit, while short-tailed AMPAR subunits GluA2/3 also start being expressed. PKA is becoming the dominant kinase. C, in the third and fourth weeks after birth spine numbers increase exponentially. Two types of AMPARs dominate from this time onward: GluA1/2s and GluA2/3s. The kinase PKC is reaching maximal levels. CaMKII and calcineurin (PP2B) expression levels are rising. D, when the rodent is mature, spine numbers maximize, the developmental switch of GluN2B to GluN2A has occurred and CaMKII and calcineurin (PP2B) have reached maximal levels.