Induction of Hebbian and non-Hebbian mossy fiber long-term potentiation by distinct patterns of high-frequency stimulation

The synapse made by hippocampal messy fibers onto pyramidal neurons of hippocampal area CA3 displays a form of longterm potentiation (LTP) that is independent of the activation of NMDA receptors. Considerable controversy exists as to whether the induction of messy fiber LTP requires postsynaptic activation and, thus, whether messy fiber LTP is Hebbian or non-Hebbian. Here we report the induction of both Hebbian and non-Hebbian forms of long-term potentiation at the messy fiber-CA3 synapse in in vitro slice preparation. These two forms of potentiation can be induced selectively by different induction conditions. Sustained presynaptic activation is sufficient to induce the non-Hebbian form of messy fiber LTP, whereas brief presynaptic activation coincident with postsynaptic depolarization is required to induce the Hebbian form. We suggest that non-Hebbian forms of plasticity may play an important role in dynamically regulating the thresholds for inducing Hebbian forms of plasticity.