Interaction Between Theta Phase and Spike Timing-Dependent Plasticity Simulates Theta-Induced Memory Effects

Rodent studies suggest that spike timing relative to hippocampal theta activity determines whether potentia-tion or depression of synapses arise. Such changes also depend on spike timing between presynaptic and postsynaptic neurons, known as spike timing-dependent plasticity (STDP). STDP, together with theta phase -dependent learning, has inspired several computational models of learning and memory. However, evidence to elucidate how these mechanisms directly link to human episodic memory is lacking. In a computational model, we modulate long-term potentiation (LTP) and long-term depression (LTD) of STDP, by opposing phases of a simulated theta rhythm. We fit parameters to a hippocampal cell culture study in which LTP and LTD were observed to occur in opposing phases of a theta rhythm. Further, we modulated two inputs by co-sine waves with 0 degrees and asynchronous phase offsets and replicate key findings in human episodic memory. Learning advantage was found for the in-phase condition, compared with the out-of-phase conditions, and was specific to theta-modulated inputs. Importantly, simulations with and without each mechanism suggest that both STDP and theta phase-dependent plasticity are necessary to replicate the findings. Together, the re-sults indicate a role for circuit-level mechanisms, which bridge the gap between slice preparation studies and human memory.