Postnatal development of zinc-containing cells and neuropil in the hippocampal region of the mouse.

The present study describes the postnatal development of zinc-containing boutons and their neurons of origin in the hippocampal region of the mouse. Ages investigated for the development of zinc-containing neuropil were postnatal days 0 (P0), P3, P7, P11, P15, P21, and P28. For zinc-containing cell bodies P7, P15, P21, and P28 were studied. In the area dentata, zinc-containing neuropil appeared first by P3 adjacent to the suprapyramidal limb of the granule cell layer and extended later toward the infrapyramidal limb. By P15, inter- and intralaminar gradients corresponded to those seen in adult animals. The appearance of labeled granule cells followed closely, although temporally delayed, the pattern of granule cell neurogenesis. All granule cells were labeled by P28. In the hippocampus proper, zinc-containing neuropil was seen by P0, but staining of the incipient mossy fiber zone was first visible by P3. Staining pattern and intensity developed gradually until they reached their mature appearance by P15. The distribution of labeled cells was identical to that seen in mature animals by P7 in CA3, but first by P21 in CA1. In the subiculum, neuropil staining first appeared proximally by P7, included all of this area by P11, and appeared mature by P21. A few labeled cells were seen in the proximal subiculum at all ages at which labeled cells were present in CA1. Labeled cells which extended further distally became first visible by P21. Their number and labeling intensity reached mature levels by P28. In the presubiculum, retrosplenial area 29e, and parasubiculum, neuropil staining first appeared by P3. The retrosplenial area 29e could be distinguished by P11. This area and the presubiculum reached their adult appearance by P21. This occurred first by P28 in the parasubiculum due to the late maturation of the parasubiculum a. Labeled cells were first seen by P7 in layer III of the presubiculum and by P15 in the retrosplenial area 29e and the parasubiculum. Cell labeling appeared mature by the same times as the neuropil staining. In the entorhinal areas a very light neuropil stain was apparent in the deeper layers by P0. A distinct rise in staining intensity was first observed by P7 in layers I-III. Thereafter, mature characteristics developed gradually and were attained by P21. Cell labeling was not seen in the medial entorhinal area. A few labeled cells were apparent by P7 in the lateral entorhinal area. After a slight increase by P15, numerous labeled cells were found in layer II and layer VI by P21. Their distribution and labeling intensity appeared mature by P28. Zinc-containing cells appear to represent cells formed late in the course of neurogenesis in all areas aside from the lateral entorhinal area. As far as intrinsic connections are concerned, it is the development of projections from this subset of neurons which is monitored in this study. We suggest that the appearance of zinc may contribute via its different effects on N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors to the end of a developmental phase that is permissive to changes in synaptic efficacy. Species differences and alternative functions of zinc are considered.