Choline induces opposite changes in pyramidal neuron excitability and synaptic transmission through a nicotinic receptor-independent process in hippocampal slices.
Choline is present at cholinergic synapses as a product of acetylcholine degradation. In addition, it is considered a selective agonist for α5 and α7 nicotinic acetylcholine receptors (nAChRs). In this study, we determined how choline affects action potentials and excitatory synaptic transmission using extracellular and intracellular recording techniques in CA1 area of hippocampal slices obtained from both mice and rats. Choline caused a reversible depression of evoked field excitatory postsynaptic potentials (fEPSPs) in a concentration-dependent manner that was not affected by α7 nAChR antagonists. Moreover, this choline-induced effect was not mimicked by either selective agonists or allosteric modulators of α7 nAChRs. Additionally, this choline-mediated effect was not prevented by either selective antagonists of GABA receptors or hemicholinium, a choline uptake inhibitor. The paired pulse facilitation paradigm, which detects whether a substance affects presynaptic release of glutamate, was not modified by choline. On the other hand, choline induced a robust increase of population spike evoked by orthodromic stimulation but did not modify that evoked by antidromic stimulation. We also found that choline impaired recurrent inhibition recorded in the pyramidal cell layer through a mechanism independent of α7 nAChR activation. These choline-mediated effects on fEPSP and population spike observed in rat slices were completely reproduced in slices obtained from α7 nAChR knockout mice, which reinforces our conclusion that choline modulates synaptic transmission and neuronal excitability by a mechanism independent of nicotinic receptor activation.
Department of Pharmacology and Therapeutic, University Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029, Madrid, Spain.|Instituto Teófilo Hernando, Facultad de Medicina, University Autónoma de Madrid, 28029, Madrid, Spain.
E
E
Albiñana
Department of Pharmacology and Therapeutic, University Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029, Madrid, Spain.|Instituto Teófilo Hernando, Facultad de Medicina, University Autónoma de Madrid, 28029, Madrid, Spain.
J G
JG
Luengo
Department of Pharmacology and Therapeutic, University Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029, Madrid, Spain.|Instituto Teófilo Hernando, Facultad de Medicina, University Autónoma de Madrid, 28029, Madrid, Spain.
A M
AM
Baraibar
Servicio de Neurología Experimental, Hospital Universitario Ramón y Cajal, IRYCIS, 28034, Madrid, Spain.
M D
MD
Muñoz
Department of Pharmacology and Therapeutic, University Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029, Madrid, Spain.|Instituto Teófilo Hernando, Facultad de Medicina, University Autónoma de Madrid, 28029, Madrid, Spain.
L
L
Gandía
Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, 28034, Madrid, Spain.
J M
JM
Solís
Department of Pharmacology and Therapeutic, University Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029, Madrid, Spain. jesusmiguel.hernandez@uam.es.|Instituto Teófilo Hernando, Facultad de Medicina, University Autónoma de Madrid, 28029, Madrid, Spain. jesusmiguel.hernandez@uam.es.
J M
JM
Hernández-Guijo
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002794:Choline / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials; D018756:GABA Antagonists / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000494:pharmacology; D008297:Male; D051379:Mice; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
D018678:Cholinergic Agents; D018756:GABA Antagonists; D011978:Receptors, Nicotinic; D006426:Hemicholinium 3; D002794:Choline
Acetylcholine; Choline; Hippocampal neurons; Intrinsic excitability; Nicotinic receptors; Population spikes; Recurrent inhibition; Synaptic transmission; fEPSP