A voltage-based metaplasticity rule applied to the model hippocampal granule cell accounts for homeostatic heterosynaptic plasticity

Long-term potentiation (LTP) and long-term depression (LTD) of synaptic efficacies are involved in establishment of long-term memories. In this process, neurons need to adjust the overall efficacy of their synapses by using mechanisms of homeostatic plasticity to balance their activity and control their firing rate. For instance, in the dentate granule cell in vivo, induction of homosynaptic LTP in the tetanized medial perforant path is accompanied by heterosynaptic LTD in the non-tetanized lateral perforant path. We used the compartmental model of this cell to test the following hypotheses: 1. Using plasticity and metaplasticity rules both based on postsynaptic voltage we can reproduce homosynaptic LTP and concurrent heterosynaptic LTD, provided there is an ongoing noisy spontaneous activity; 2. Frequency of an ongoing noisy spontaneous activity along the lateral path determines the magnitude of heterosynaptic LTD. In experiments where procaine was used to block the lateral spontaneous activity, no heterosynaptic LTD occurred. However, when the procaine was washed out and a second tetanization was applied to the medial path, no heterosynaptic LTD could have been induced neither. Our simulations predict that the reduced frequency of spontaneous activity in the lateral perforant path can account for this lasting absence of heterosynaptic LTD.