Irregular and bursty neuronal firing extend spike-timing dependent plasticity window to behavioral timescales

Synaptic plasticity, which is thought to underlie learning and memory, is commonly induced in experimental settings with regular activity patterns. However, such regularity strongly differs from natural in vivo firing statistics. Therefore, it remains unclear how in vivo-like patterns, such as irregular and bursty activity, shape synaptic plasticity. We combined mathematical modeling and ex vivo patch-clamp experiments inducing naturalistic spike-timing-dependent plasticity (STDP) at cortico-striatal synapses. We found that irregular spike-pair stimulation diminished LTD occurrence and widened the LTP temporal window compared to regular patterns at low firing rate. Furthermore, increasing the firing rate abolished LTD to the profit of LTP. Our modeling and experimental data indicate that bursts of action potentials are key contributors to this effect. These results highlight the importance of naturalistic firing statistics and show that irregular and bursty firings extend the typical compressed STDP expression temporal window toward timescales relevant for behavior.