A non-alpha7 nicotinic acetylcholine receptor modulates excitatory input to hippocampal CA1 interneurons.
The nicotinic acetylcholine receptor (nAChR), particularly the alpha7 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 alpha3beta4-containing nAChRs in the modulation of interneuron EPSCs. Ligands selective for the alpha7 nAChR had very little or no effect on interneuron EPSCs. Low concentrations of nicotine also enhanced EPSC frequency, implicating the involvement of non-alpha7 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-alpha7 nAChR, presumably alpha3beta4, controls glutamate transmission to CA1 interneurons.
Alkondon
Manickavasagom
M
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
Albuquerque
Edson X
EX
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines; D002794:Choline / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D007395:Interneurons / Q000502:physiology*; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011807:Quinolizines; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000093843:Quinolizidine Alkaloids
D000109:Acetylcholine; D000470:Alkaloids; D001392:Azocines; D002794:Choline; D004079:Dihydro-beta-Erythroidine; D004246:Dimethylphenylpiperazinium Iodide; D008464:Mecamylamine; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579165:Chrna7 protein, rat; C403530:nicotinic receptor alpha3beta4; C403531:nicotinic receptor alpha4beta2; C004712:cytisine; D000093843:Quinolizidine Alkaloids