In Hippocampal Oriens Interneurons Anti-Hebbian Long-Term Potentiation Requires Cholinergic Signaling via α7 Nicotinic Acetylcholine Receptors

In the hippocampus, at excitatory synapses between principal cell and oriens/alveus (O/A) interneurons, a particular form of NMDA-independent long-term synaptic plasticity (LTP) has been described (Lamsa et al., 2007). This type of LTP occurs when presynaptic activation coincides with postsynaptic hyperpolarization. For this reason it has been named anti-Hebbian to distinguish from the classical Hebbian type of associative learning where presynaptic glutamate release coincides with postsynaptic depolarization. The different voltage dependency of LTP induction is thought to be mediated by calcium-permeable (CP) AMPA receptors that, due to polyamine-mediated rectification, favor calcium entry at hyperpolarized potentials. Here, we report that the induction of this form of LTP needs CP-alpha 7 nicotinic acetylcholine receptors (nAChRs) that, like CP-AMPARs, exhibit a strong inward rectification because of polyamine block at depolarizing potentials. We found that high-frequency stimulation of afferent fibers elicits synaptic currents mediated by alpha 7 nAChRs. Hence, LTP was prevented by alpha 7 nAChR antagonists dihydro-beta-erythroidine and methyllycaconitine (MLA) and was absent in alpha 7(-/-) mice. In addition, in agreement with previous observations (Le Duigou and Kullmann, 2011), in a minority of O/A interneurons in MLA-treated hippocampal slices from WT animals and alpha 7(-/-) mice, a form of LTP probably dependent on the activation of group I metabotropic glutamate receptors was observed. These data indicate that, in O/A interneurons, anti-Hebbian LTP critically depends on cholinergic signaling via alpha 7 nAChR. This may influence network oscillations and information processing.