Cholinergic coordination of presynaptic and postsynaptic activity induces timing-dependent hippocampal synaptic plasticity.

Correlated presynaptic and postsynaptic activity is the key factor in inducing Hebbian plasticity and memory. However, little is known about the physiological events that could mediate such coordination. Correlated cholinergic input induces spike timing-dependent plasticity-like hippocampal synaptic plasticity. Cholinergic receptors are localized to both presynaptic and postsynaptic glutamatergic sites and thus have the potential to coordinate presynaptic and postsynaptic activity to induce plasticity. By directly monitoring presynaptic and postsynaptic activities with genetically encoded calcium indicators in mouse septohippocampal cocultures, we found interactive but independent presynaptic and postsynaptic modulations in the cholinergic-dependent synaptic plasticity. Neither presynaptic nor postsynaptic modulation alone is sufficient, but instead a coordinated modulation at both sites is required to induce the plasticity. Therefore, we propose that correlated cholinergic input can coordinate presynaptic and postsynaptic activities to induce timing-dependent synaptic plasticity, providing a novel mechanism by which neuromodulators precisely modulate network activity and plasticity with high efficiency and temporal precision.