Computational examination of synaptic plasticity and metaplasticity in hippocampal dentate granule neurons

Long-term potentiation (LTP) and long-term depression (LTD) are two forms of long-lasting synaptic plasticity. To protect synaptic weights from extreme increase or decrease, neurons need to regulate their activities; this phenomenon is called homeostatic plasticity. The induction of homosynaptic plasticity by high-frequency stimulation (HFS) increases the strength of synaptic weights dramatically which makes a neuron loses balance. However, heterosynaptic plasticity keeps the synaptic weights away from the extreme increase and brings them into a stable range. Therefore, neurons need both homosynaptic and heterosynaptic plasticity to regulate their synaptic weights. In most previous studies of spike-timing-dependent plasticity (STDP) models, postsynaptic spikes are treated as all-or-none events; however, in this study, we calculate the voltage of the postsynaptic spikes instead of counting the number of spikes. Further, we incorporate a modified model of metaplasticity based on the voltage of the spike rather than the spike count. To model synaptic plasticity of dentate granule cells, we used computational simulations and employed STDP rules accompanied with metaplasticity model and noisy spontaneous activity to address these questions; firstly, could our plasticity and metaplasticity models produce homosynaptic LTP in one pathway and heterosynaptic LTD in the neighbouring pathway? Secondly, does the magnitude of spontaneous activity after stimulation determine the level of heterosynaptic LTD? Thirdly, when two stimulations with the same frequency are applied to the same synapse at different time interval, will both stimulations produce the same level of synaptic plasticity? Our result shows that employing STDP and metaplasticity rules based on the voltage of the spikes accompanied with noisy spontaneous activity could replicate homosynaptic LTP in the stimulated pathway and heterosynaptic LTD in the non-stimulated neighbouring pathway of the dentate granule cell, as shown experimentally (Abraham WC, Mason-Parker SE, Bear MF, Webb S, Tate WP, Proc Natl Acad Sci 98(19):10924-10929, 2001; Abraham WC, Logan B, Wolff A, Benuskova L, J Neurophysiol 98(2):1048-1051, 2007).