Transient synaptic zinc-positive thalamocortical terminals in the developing barrel cortex.

In rat barrel cortex, layer 4 has a transiently high density of zinc-positive terminations from postnatal day (P)9 to P12 [P.W. Land & L. Shamalla-Hannah (2002)J. Comp. Neurol., 447, 43-56]. These terminations have been proposed to originate from cortico-cortical connections, but their exact origin is unknown. To determine their sources, we injected sodium selenite into the barrel cortex of two adult rats and 32 pups, from P5 to P28. As predicted, abundant zinc-positive cortically projecting neurons were visible around the injection sites and in distant cortical areas. From P9 to P13, however, neurons retrogradely labeled by zinc selenite occurred in the thalamus, in topographically appropriate regions of the ventroposterior medial (VPM) and posterior nuclei (Po). Because there are no previous reports of zinc-positive sensory thalamocortical connections, we sought corroboration of this unexpected finding by electron microscopy. This revealed a subset of boutons in layers 4 and 1, positive for both zinc and vesicular glutamate transporter 2, a protein used by thalamocortical terminations. Finally, in an additional nine rats, we carried out in situ hybridization for zinc transporter 3 mRNA. Moderate signal was detected in VPM and Po at P10, but this disappeared by P28. In contrast, a strong signal was apparent in the anterodorsal nucleus, which projects to limbic areas, and this persisted at P28. The timing of the transient zinc-positive terminations in the sensory thalamus roughly coincides with the onset of exploratory and whisking behavior in the middle of the second postnatal week; and this suggests zinc is important for activity-related refinement of circuitry.