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 potentiation or depression of synapses arise. Such changes also depend on spike timing between pre- and post-synaptic 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 cosine waves with 0° and asynchronous phase offsets and replicate key findings in human episodic memory. Learning advantage was found for the in-phase condition, as compared to 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 results indicate a role for circuit-level mechanisms, which bridges the gap between slice preparation studies and human memory. Significance Statement Long-lasting changes in synaptic connectivity between neurons have been suggested to support learning and memory processes at the cellular level in the brain. Direct evidence on how this cellular mechanism links to human memory behaviour is lacking. To investigate this, we constructed a computational model that implements two synaptic plasticity mechanisms that are well-established in rodent studies. One mechanism suggests that strengthening or weakening in synaptic connectivity depends on the phase of ongoing theta activity. The other mechanism suggests that synaptic modification depends on spike timing between two neurons. Our model successfully reproduces results from rodent studies, as well as human episodic memory studies. These findings suggest a link between learning mechanisms at the cellular level and human associative memory.