NEUROSCIENCE Choline induces opposite changes in pyramidal neuron excitability and synaptic transmission through a nicotinic receptor-independent process in hippocampal slices E. Albiñana 1,2 & J.G. Luengo 1,2 & A.M. Baraibar 1,2 & M.D. Muñoz 3 & L. Gandía 1,2 & J.M. Solís 4 & J.M. Hernández-Guijo 1,2 Received: 23 December 2016 /Revised: 17 January 2017 /Accepted: 19 January 2017 # Springer-Verlag Berlin Heidelberg 2017 Abstract Choline is present at cholinergic synapses as a product of acetylcholine degradation. In addition, it is considered a selec- tive agonist for α5 and α7 nicotinic acetylcholine receptors (nAChRs). In this study, we determined how choline affects action potentials and excitatory synaptic transmission using ex- tracellular 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 post- synaptic potentials (fEPSPs) in a concentration-dependent man- ner 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 up- take inhibitor. The paired pulse facilitation paradigm, which de- tects whether a substance affects presynaptic release of gluta- mate, 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 anti- dromic stimulation. We also found that choline impaired recur- rent inhibition recorded in the pyramidal cell layer through a mechanism independent of α7 nAChR activation. These choline-mediated effects on fEPSP and population spike ob- served in rat slices were completely reproduced in slices obtained from α7 nAChR knockout mice, which reinforces our conclu- sion that choline modulates synaptic transmission and neuronal excitability by a mechanism independent of nicotinic receptor activation. Keywords Synaptic transmission . fEPSP . Population spikes . Nicotinic receptors . Hippocampal neurons . Acetylcholine . Choline . Recurrent inhibition . Intrinsic excitability Introduction Acetylcholine-activated receptors modulate neuronal excit- ability, neurotransmitter release [1, 33, 46, 48, 56, 74] and synaptic plasticity. Thereby, they participate in several learn- ing and memory processes [13, 16, 17, 19, 22, 24, 27, 45, 54, 80, 81]. Alterations of nicotinic cholinergic mechanisms con- tribute to brain dysfunctions such as epilepsy, schizophrenia and Alzheimer’ s disease [18]. In fact, some agents that regu- late cholinergic transmission have been proposed as a thera- peutic intervention for the treatment of various neurodegener- ative disorders [8, 39]. Cholinergic neurotransmission is tightly linked to other neurotransmitter systems. In this sense, α7 nicotinic acetyl- choline receptors (nAChRs) modulate the release of several neurotransmitters, including glutamate [33, 46, 56], GABA [1], dopamine [74] and noradrenaline [48]. This may explain why activation of α7 nAChRs is involved in the regulation of interneuron excitability [29], long-term potentiation (LTP) in- duction [52] and neuroprotection [47]. * J.M. Hernández-Guijo jesusmiguel.hernandez@uam.es 1 Department of Pharmacology and Therapeutic, University Autónoma de Madrid, Av. Arzobispo Morcillo 4, 28029 Madrid, Spain 2 Instituto Teófilo Hernando, Facultad de Medicina, University Autónoma de Madrid, 28029 Madrid, Spain 3 Servicio de Neurología Experimental, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain 4 Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain Pflugers Arch - Eur J Physiol DOI 10.1007/s00424-017-1939-5