Identification of upregulated SCG10 mRNA expression associated with late-phase long-term potentiation in the rat hippocampal Schaffer-CA1 pathway in vivo.

The maintenance of long-term potentiation (LTP) depends on alteration of gene transcription. By screening a subtracted cDNA library that is enriched in upregulated transcripts in rat hippocampus 3 hr after Schaffer-CA1 LTP induction in vivo, we identified a neural growth-associated protein SCG10 (superior cervical ganglia clone 10) gene. The semiquantitative reverse transcription-PCR and Northern blot experiments confirmed that SCG10 mRNA levels were elevated in tetanized rat hippocampi compared with those of sham controls that received only low-frequency stimulation. Both 1 and 2 kb forms of SCG10 mRNAs contributed to the increased expression. Using a riboprobe with a sequence specific to the 3'-untranslated region of rat SCG10 mRNA, in situ hybridization further revealed a significant increase of the SCG10 mRNA 2 kb form in the ipsilateral CA3 and CA1 regions of LTP animals. In addition, we systemically injected the competitive NMDA receptor antagonist d,l-3[(+/-)-2-carboxypiperazine-4-yl]-propyl-1-phosphonic acid (CPP) to determine whether the alteration of SCG10 expression depends on NMDA receptor activation or tetanus alone. Administration of CPP 1 hr before tetanus completely blocked LTP induction and the increase of SCG10 mRNA levels. Thus, these results suggest that the transcription of SCG10 in vivo is regulated by long-lasting synaptic activity and may contribute to the maintenance of long-term synaptic plasticity via a presynaptic remodeling mechanism.