Nicotine facilitates long-term potentiation induction in oriens-lacunosum moleculare cells via Ca2+ entry through non-α7 nicotinic acetylcholine receptors

Hippocampal inhibitory interneurons have a central role in the control of network activity, and excitatory synapses that they receive express Hebbian and anti-Hebbian long-term potentiation (LTP). Because many interneurons in the hippocampus express nicotinic acetylcholine receptors (nAChRs), we explored whether exposure to nicotine promotes LTP induction in these interneurons. We focussed on a subset of interneurons in the stratum oriens/alveus that were continuously activated in the presence of nicotine due to the expression of non-desensitizing non-alpha 7 nAChRs. We found that, in addition to alpha 2 subunit mRNAs, these interneurons were consistently positive for somatostatin and neuropeptide Y mRNAs, and showed morphological characteristics of oriens-lacunosum moleculare cells. Activation of non-alpha 7 nAChRs increased intracellular Ca2+ levels at least in part via Ca2+ entry through their channels. Presynaptic tetanic stimulation induced N-methyl-D-aspartate receptor-independent LTP in voltage-clamped interneurons at -70 mV when in the presence, but not absence, of nicotine. Intracellular application of a Ca2+ chelator blocked LTP induction, suggesting the requirement of Ca2+ signal for LTP induction. The induction of LTP was still observed in the presence of ryanodine, which inhibits Ca2+-induced Ca2+ release from ryanodine-sensitive intracellular stores, and the L-type Ca2+ channel blocker nifedipine. These results suggest that Ca2+ entry through non-alpha 7 nAChR channels is critical for LTP induction. Thus, nicotine affects hippocampal network activity by promoting LTP induction in oriens-lacunosum moleculare cells via continuous activation of non-alpha 7 nAChRs.