Hippocampal Interneuronal alpha 7 nAChRs Modulate Theta Oscillations in Freely Moving Mice

Muscarinic acetylcholine receptors (mAChRs) are critically involved in hippocampal theta generation, but much less is known about the role of nicotinic AChRs (nAChRs). Here we provide evidence that alpha 7 nAChRs expressed on interneurons, particularly those in oriens lacunosum moleculare (OLM), also regulate hippocampal theta generation. Local hippocampal infusion of a selective alpha 7 nAChR antagonist significantly reduces hippocampal theta power and impairs Y-maze spontaneous alternation performance in freely moving mice. By knocking out receptors in different neuronal subpopulations, we find that alpha 7 nAChRs expressed in OLM interneurons regulate theta generation. Our in vitro slice studies indicate that alpha 7 nAChR activation increases OLM neuron activity that, in turn, enhances pyramidal cell excitatory postsynaptic currents (EPSCs). Our study also suggests that mAChR activation promotes transient theta generation, while alpha 7 nAChR activation facilitates future theta generation by similar stimulations, revealing a complex mechanism whereby cholinergic signaling modulates different aspects of hippocampal theta oscillations through different receptor subtypes.