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Long vs short-term synaptic learning rules after optogenetic spike-timing-dependent plasticity

Spike-timing-dependent plasticity (STDP) is a candidate mechanism for information storage in the brain. However, it has been practically impossible to assess the long-term consequences of STDP because recordings from postsynaptic neurons last at most one hour. Here we introduce an optogenetic method to, with millisecond precision, independently control action potentials in two neuronal populations with light. We apply this method to study spike-timing-dependent plasticity (oSTDP) in the hippocampus and reproduce previous findings that depression or potentiation depend on the sequence of pre- and postsynaptic spiking. However, 3 days after induction, oSTDP results in potentiation regardless of the exact temporal sequence, frequency or number of pairings. Blocking activity between induction and readout prevented the synaptic potentiation, indicating that strengthened synapses have to be used to get strong. Our findings indicate that STDP potentiates synapses and that the change in synaptic strength persist to behaviorally relevant timescales.