Different requirements for action potentials in the induction of different forms of long-term potentiation

The role of postsynaptic action potentials (APs) in the induction of long-term potentiation (LTP) remains unclear, but has important implications for theories of associative learning in the brain. In area CA1 of hippocampus, at least three discrete forms of LTP coexist, each displaying unique decay kinetics and involving different signalling and effector systems. The present work investigates whether these forms of LTP also differ in their requirement for postsynaptic APs. Inhibition of APs during theta-burst stimulation (TBS) had no effect on the persistence of short-lasting LTP (LTP 1), but reduced the persistence of more durable forms (LTP 2 and 3). Calcium imaging revealed different requirements for APs in generating calcium signals in spines, dendrites, and somata, consistent with their known roles in the induction of each form of LTP. Finally, short-lasting LTP was endowed with dramatically enhanced persistence by the presentation of TBS-patterned APs alone. These data reveal that the requirement for APs in LTP induction is dependent on the form of LTP under investigation, supporting the contention that different neuronal learning mechanisms coexist in hippocampal area CA1.