Axonal remodeling during postnatal maturation of CA3 hippocampal pyramidal neurons

Abstract

Anatomical substrates were investigated for local circuit hyperexcitability that occurs in the CA3 subfield of the rat hippocampus during postnatal week 2. A transient excess of excitatory local circuit connectivity was hypothesized to underlie this hyperexcitability. To test this hypothesis, recurrent excitatory axon arbors from single biocytin-filled CA3 pyramidal cells were reconstructed. Arbors were analyzed in segments of area CA3 comparable in size to in vitro minislice preparations, which were shown to reproduce the developmental hyperexcitability seen in intact slices during postnatal week 2. Segments were then adjusted for hippocampal growth, based on age-dependent changes in neuron density in stratum pyramidale. Axon arbors were found to be short and possessed very few branches during the first postnatal week. By the second postnatal week, arbors had undergone dramatic growth and were much longer and more complex in their branching patterns. By adulthood, a significant decrease in all measures of arbor length and complexity was observed. Following growth adjustment, measures of axon length and varicosity number during week 2 were not significantly different from that of adulthood. However, the number of axon branches decreased by 50%. These results suggest that, during early postnatal life, there is exuberant outgrowth of local CA3 recurrent axons, and with maturation these recurrent collaterals are remodeled. Short-ranging, profusely branched axons appear to be replaced by longer-ranging arbors that possess fewer branches. Maturational changes in the dendritic location rather than the number of early-formed recurrent excitatory synapses may explain developmental hyperexcitability of the hippocampal CA3 subfield.