Activity-dependent metaplasticity of direct cortical inputs in the rat hippocampal CA3 pyramidal neuron

Abstract

The intrinsic excitability of neurons plays an important role in the encoding of memory and in the coupling of synaptic inputs to spike generation. Recently, we report that repetitive somatic firing with physiologically relevant frequency induces internalization of Kv1.2 from distal dendrites of hippocampal CA3 pyramidal cells (CA3-PCs), resulting in long-term potentiation of intrinsic excitability (LTP-IE). We posed a question whether LTP-IE has any differential influences on the synaptic modulation at distal and intermediate dendritic intputs, which are carried by perforant path (PP) and associational/commissural (A/C) fiber, respectively. I monitored the excitatory postsynaptic potentials (EPSPs) every 8 s at PP-CA3 synapses and AC-CA3 synapses before and after conditioning (a train of 20 somatic action potentials at 10 Hz) in CA3 PC. This conditioning induced a potentiation of EPSPs but not EPSCs at PP-CA3 synapses, whereas the same priming signal altered neither EPSCs nor EPSPs at AC-CA3 synapses. To study the effect of LTP-IE on metaplsticity at PP-CA3 synapses, I first determined the threshold in the strength of PP stimulation for induction of long-term potentiation (LTP) at PP-CA3 synapses. I found that minimal stimulation of PP-CA3 synapses at high frequency (weak HFS) by itself was below the threshold of LTP induction. The weak HFS of PP induced neither EPSP-to-spike (E-S) potentiation nor LTP under control conditions. After the induction of LTP-IE, however, weak HFS readily induced E-S potentiation and LTP at the PP-CA3 synapses. These results indicate that LTP-IE in the CA3-PCs enhances E-S coupling specifically at the PP synapses, which in turn facilitates memory formation at the same synapse under Hebbian rule.