A Non-α7 Nicotinic Acetylcholine Receptor Modulates Excitatory Input to Hippocampal CA1 Interneurons

Abstract

The nicotinic acetylcholine receptor (nAChR), particularly the α7 subtype, has received profound attention for its role in modifying excitatory postsynaptic currents (EPSCs) in hippocampal pyramidal neurons as well as in neurons from other brain regions. Here, we tested the possibility that an nAChR could affect EPSCs in the interneurons of rat hippocampal slices. Using whole-cell patch-clamp technique on CA1 stratum radiatum interneurons and U-tube application of agents, we show that nicotinic agonists enhance EPSC frequency in interneurons. Among the agents tested, cytisine and mecamylamine were the most effective agonist and antagonist, respectively, suggesting a role for α3β4-containing nAChRs in the modulation of interneuron EPSCs. Ligands selective for the α7 nAChR had very little or no effect on interneuron EPSCs. Low concentrations of nicotine also enhanced EPSC frequency, implicating the involvement of non-α7 nAChRs in controlling interneuron excitability in smokers. We conclude that nAChR-dependent EPSC modulation in the hippocampus is both subtype- and neuron-specific and that a non-α7 nAChR, presumably α3β4, controls glutamate transmission to CA1 interneurons.