Two elements of neural information processing have primarily been proposed: firing rate and spike timing of neurons. In the case of synaptic plasticity, although spike-timing-dependent plasticity (StDp) depending on presynaptic and postsynaptic spike times had been considered the most common rule, recent studies have shown the inhibitory nature of the brain in vivo for precise spike timing, which is key to the STDP. Thus, the importance of the firing frequency in synaptic plasticity in vivo has been recognized again. However, little is understood about how the frequency-dependent synaptic plasticity (FDP) is regulated in vivo. Here, we focused on the presynaptic input pattern, the intracellular calcium decay time constants, and the background synaptic activity, which vary depending on neuron types and the anatomical and physiological environment in the brain. By analyzing a calcium-based model, we found that the synaptic weight differs depending on these factors characteristic in vivo, even if neurons receive the same input rate. This finding suggests the involvement of multifaceted factors other than input frequency in fDp and even neural coding in vivo. Synaptic plasticity in neural networks is a substrate of learning and memory, which includes both positive and negative components, i.e., both long-lasting enhancements and declines in the weight of synaptic transmission (long-term potentiation (LTP) and long-term depression (LTD)) 1. Many experimental studies have suggested two plausible mechanisms for the induction of the synaptic plasticity 2,3. The first is the frequency of spike trains, which has been studied in association with the Bienenstock, Cooper, and Munro (BCM) rule in classical research conducted approximately half a century ago 4-6. LTP is induced by high-frequency firing in presynaptic neurons, which produces large increases in postsynaptic calcium concentration 5-8. The low-frequency firing causes a modest increase in the calcium level, and thereby induces LTD 9-11. The second is the precise timing of presynaptic and postsynaptic firing, which has been investigated as spike-time-dependent plasticity (STDP) in numerous experimental and theoretical studies from approximately 20 years ago 12-15. LTP is induced by the presynaptic action potentials preceding postsynaptic spikes by no more than tens of milliseconds, whereas presynaptic firing that follows postsynaptic spikes produces LTD 13,14,16-19. The idea that STDP plays a central role in synaptic plasticity had been becoming mainstream. Recent studies have reported, however, that in some cases, the environment in vivo may not be suitable for precise spike timing, which is key to the STDP. Pre-and post-synaptic neurons in the primary visual cortex and extrastriate cortex of awaking animals fire so irregularly that the timing of presynaptic and postsynaptic firing varies 20-22. Neurons and synapses in the cerebral cortex of rats receive a lot of background neuronal activity that is generated internally, which provides strong constraints on spike ti...

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Synaptic plasticity is vital for learning and memory in the brain. It consists of long-term potentiation (LTP) and long-term depression (LTD). Spike frequency is one of the major components of synaptic plasticity in the brain, a noisy environment. Recently, we mathematically analyzed the frequency-dependent synaptic plasticity (FDP) in vivo and found that LTP is more likely to occur with an increase in the frequency of background synaptic activity. Meanwhile, previous studies suggest statistical fluctuation in the amplitude of background synaptic activity. Little is understood, however, about its contribution to synaptic plasticity. To address this issue, we performed numerical simulations of a calcium-based synapse model. Then, we found attenuation of the tendency to become LTD due to an increase in the fluctuation of background synaptic activity, leading to an enhancement of synaptic weight. Our result suggests that the fluctuation affects synaptic plasticity in the brain.

Synaptic plasticity is vital for learning and memory in the brain. It consists of long-term potentiation (LTP) and long-term depression (LTD). Spike frequency is one of the major components of synaptic plasticity in the brain, a noisy environment. Recently, we mathematically analysed the frequency-dependent synaptic plasticity (FDP) in vivo and found that LTP is more likely to occur with an increase in the frequency of background synaptic activity. Previous studies suggest fluctuation in the amplitude of background synaptic activity. However, little is understood about the relationship between synaptic plasticity and the fluctuation in the background synaptic activity. To address this issue, we performed numerical simulations of a calcium-based synapse model. Then, we found attenuation of the tendency to become LTD due to an increase in the fluctuation of background synaptic activity, leading to an enhancement of synaptic weight. Our result suggests that the fluctuation affect synaptic plasticity in the brain.