MAINTENANCE OF LATE-PHASE LTP IS ACCOMPANIED BY PKA-DEPENDENT INCREASE IN AMPA RECEPTOR SYNTHESIS

Long-term potentiation (LTP) is a form of synaptic plasticity that has been extensively studied as a putative mechanism underlying learning and memory. A late phase of LTP occurring 3-5 hours after stimulation and depending on transcription, protein synthesis and cyclic-AMP-depen dent protein kinase (protein kinase A, or PKA) has been described(1-3) , but it is not known whether transcription of presynaptic and/or post synaptic genes is required to support late-phase LTP. Here we show tha t late-phase LTP can be obtained in rat hippocampal CA1 mini-slices in which the cell bodies of presynaptic Schaffer collateral/ commissural fibres are rr moved. Thus, transcription of presynaptic genes is not necessary to support maintenance of late-phase LTP. The AMPA (alpha-am ino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor is the predomi nant mediator of the ionotropic response to synaptically released glut amate in the hippocampus and it has been implicated in LTP maintenance . We find that synthesis of AMPA receptor subunits is increased three hours after LTP induction: this effect on the synthesis of the AMPA re ceptor is blocked by inhibitors of PKA and of transcription. Our resul ts support the idea of a postsynaptic mechanism maintaining late-phase LTP, in which AMPA receptor synthesis is increased as a result of PKA -dependent gene transcription.