Journal
CEREBRAL CORTEX
Volume 26, Issue 6, Pages 2549-2562Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhv085
Keywords
acetylcholine; neocortex; nicotinic receptors; optogenetics; synaptic transmission
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Funding
- Centre National de la Recherche Scientifique, Universite Pierre et Marie Curie-P6
- Ecole des Neurosciences de Paris (Network for Viral Transfer)
- Fondation pour la Recherche sur le Cerveau/Rotary Club de France
- Agence Nationale de la Recherche (IHU Institut de Neurosciences Translationnelles de Paris) [ANR-10-IAIHU-06]
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Nicotinic excitation in neocortex is mediated by low-affinity alpha 7 receptors and by high-affinity alpha 4 beta 2 receptors. There is evidence that alpha 7 receptors are synaptic, but it is unclear whether high-affinity receptors are activated by volume transmission or synaptic transmission. To address this issue, we characterized responses of excitatory layer 6 (L6) neurons to optogenetic release of acetylcholine (ACh) in cortical slices. L6 responses consisted in a slowly decaying alpha 4 beta 2 current and were devoid of alpha 7 component. Evidence that these responses were mediated by synapses was 4-fold. 1) Channelrhodopsin-positive cholinergic varicosities made close appositions onto responsive neurons. 2) Inhibition of ACh degradation failed to alter onset kinetics and amplitude of currents. 3) Quasi-saturation of alpha 4 beta 2 receptors occurred upon ACh release. 4) Response kinetics were unchanged in low release probability conditions. Train stimulations increased amplitude and decay time of responses and these effects appeared to involve recruitment of extrasynaptic receptors. Finally, we found that the alpha 5 subunit, known to be associated with alpha 4 beta 2 in L6, regulates short-term plasticity at L6 synapses. Our results are consistent with previous anatomical observations of widespread cholinergic synapses and suggest that a significant proportion of these small synapses operate via high-affinity nicotinic receptors.
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