Tonic nicotinic transmission enhances spinal GABAergic presynaptic release and the frequency of spontaneous network activity |
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Authors: | Brendan O'Flaherty Peter Wenner |
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Institution: | Department of Physiology, Emory University, School of Medicine, Whitehead Bldg, Room 601, Atlanta, Georgia |
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Abstract: | Synaptically driven spontaneous network activity (SNA) is observed in virtually all developing networks. Recurrently connected spinal circuits express SNA, which drives fetal movements during a period of development when GABA is depolarizing and excitatory. Blockade of nicotinic acetylcholine receptor (nAChR) activation impairs the expression of SNA and the development of the motor system. It is mechanistically unclear how nicotinic transmission influences SNA, and in this study we tested several mechanisms that could underlie the regulation of SNA by nAChRs. We find evidence that is consistent with our previous work suggesting that cholinergically driven Renshaw cells can initiate episodes of SNA. While Renshaw cells receive strong nicotinic synaptic input, we see very little evidence suggesting other spinal interneurons or motoneurons receive nicotinic input. Rather, we found that nAChR activation tonically enhanced evoked and spontaneous presynaptic release of GABA in the embryonic spinal cord. Enhanced spontaneous and/or evoked release could contribute to increased SNA frequency. Finally, our study suggests that blockade of nAChRs can reduce the frequency of SNA by reducing probability of GABAergic release. This result suggests that the baseline frequency of SNA is maintained through elevated GABA release driven by tonically active nAChRs. Nicotinic receptors regulate GABAergic transmission and SNA, which are critically important for the proper development of the embryonic network. Therefore, our results provide a better mechanistic framework for understanding the motor consequences of fetal nicotine exposure. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 298–312, 2016 |
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Keywords: | nicotinic receptor spontaneous network activity chick embryo spinal cord GABAA receptor |
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