Fetal hippocampal transplants reduce aberrant mossy fiber sprouting after CA3 pyramidal cell damage

Abstract

The CA3 pyramidal cells receive mossy fibers from the dentate granule cells, and the damage to CA3 pyramidal cells induces aberrant mossy fiber sprouting near the site of normal targets. Fetal CA1 and CA3 subregions were separately transplanted into the host CA3 subfield, where CA3 pyramidal neurons were previously damaged with kainic acid. In vitro [3H]inositol 1,4,5-trisphosphate (IP3) receptor autoradiography was used to analyze the purity of CA1 neurons. CA1 transplants had high IP3 receptor density compatible with adult CA1 subfield, while CA3 transplants had trace IP3 receptors. Animals with successful graft-host connections exhibited no aberrant mossy fiber sprouting, and mossy fibers invaded into the fetal CA3 grafts. However, animals without direct host mossy fibers-grafts connection showed aberrant mossy fiber sprouting in the CA3 subfield. These observations demonstrate that aberrant mossy fiber sprouting was suppressed by molecular cues presented on the grafted neurons and that [3H]IP3 receptor autoradiography provides an excellent marker for the identification of the CA1 pyramidal cells in grafts.