Necessity of protein synthesis in long-term potentiation (LTP) in the CA3 area of the rat hippocampus

Protein synthesis (PS) has been implicated in memory formation. Previous studies have shown PS, either near the soma or at the synapse, may contribute to the activation and establishment of various proteins needed to facilitate or maintain synaptic modifications. In the hippocampus (HC), these vibrant changes are expressed at virtually every synapse. Previous studies have shown PS dependence in the mossy fiber to CA3 and Schaffer collateral to CA1 pyramidal cells during the early phase (E-LTP) and late phase (L-LTP), respectfully. It is not known whether Long-Term Potentiation (LTP) induced at the Medial or Lateral Perforant Path (MPP, LPP) or Commissural/Associational (C/A) projections to the CA3 are dependent on PS during its E-LTP or L-LTP in-vivo. Acute extracellular responses were evoked by stimulation of LPP, MPP or C/A projections and recorded in the CA3 area of the rat HC. Protein synthesis inhibitors, anisomycin or cycloheximide were administered intracranially in the CA3 pyramidal cell layer in-vivo. Results varied with each individual pathway. The LPP results show that if either the drug is present prior to induction it blocked LTP. The application of the drug 30 minutes after induction did not block LTP, suggesting that the critical time period for PS in the LPP is immediately after HFS. The application of the drug to either MPP or C/A prior to HFS did not block LTP 1 hour after induction. Repeated application of the drug in one hour intervals for 4 hours after induction blocked LTP in these pathways. In the presence of anisomycin, neither pathway showed an effect on paired pulse stimulation, suggesting that the drug did not affect synaptic transmission. A Bradford Assay, used for protein quantification, showed a decrease in protein concentration at one and four hours after induction, this indicates that protein synthesis was inhibited in the CA3 area of the hippocampus. Therefore, these results suggest that mRNA translation is critical in these pathways at a later time intervals. Overall, these data suggest that the early phase of the LPP is protein synthesis dependent but not at MPP or C/A projections to CA3.