Acetylcholine controls GABA-, glutamate-, and glycine-dependent giant depolarizing potentials that govern spontaneous motoneuron activity at the onset of synaptogenesis in the mouse embryonic spinal cord
Journal of Neuroscience. 2014-04-30; 34(18): 6389-6404
DOI: 10.1523/JNEUROSCI.2664-13.2014
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1. J Neurosci. 2014 Apr 30;34(18):6389-404. doi: 10.1523/JNEUROSCI.2664-13.2014.
Acetylcholine controls GABA-, glutamate-, and glycine-dependent giant
depolarizing potentials that govern spontaneous motoneuron activity at the onset
of synaptogenesis in the mouse embryonic spinal cord.
Czarnecki A(1), Le Corronc H, Rigato C, Le Bras B, Couraud F, Scain AL, Allain
AE, Mouffle C, Bullier E, Mangin JM, Branchereau P, Legendre P.
Author information:
(1)Institut National de la Santé et de la Recherche Médicale, Unité Mixte de
Recherche S1130, Université Pierre et Marie Curie, Paris, Ile de France, France,
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8246,
Université Pierre et Marie Curie, Ile de France, France, Université Pierre et
Marie Curie UM CR18 Université Paris 06, Ile de France, France, Université
d’Angers, 49000 Angers, France, Université de Bordeaux, Institut de Neurosciences
Cognitives et Intégratives d’Aquitaine, Unité Mixte de Recherche 5287, F-33000
Bordeaux, France, and Centre National de la Recherche Scientifique, Institut de
Neurosciences Cognitives et Intégratives d’Aquitaine, Unité Mixte de Recherche
5287, F-33000 Bordeaux, France.
A remarkable feature of early neuronal networks is their endogenous ability to
generate spontaneous rhythmic electrical activity independently of any external
stimuli. In the mouse embryonic SC, this activity starts at an embryonic age of ∼
12 d and is characterized by bursts of action potentials recurring every 2-3 min.
Although these bursts have been extensively studied using extracellular
recordings and are known to play an important role in motoneuron (MN) maturation,
the mechanisms driving MN activity at the onset of synaptogenesis are still
poorly understood. Because only cholinergic antagonists are known to abolish
early spontaneous activity, it has long been assumed that spinal cord (SC)
activity relies on a core network of MNs synchronized via direct cholinergic
collaterals. Using a combination of whole-cell patch-clamp recordings and
extracellular recordings in E12.5 isolated mouse SC preparations, we found that
spontaneous MN activity is driven by recurrent giant depolarizing potentials. Our
analysis reveals that these giant depolarizing potentials are mediated by the
activation of GABA, glutamate, and glycine receptors. We did not detect direct
nAChR activation evoked by ACh application on MNs, indicating that cholinergic
inputs between MNs are not functional at this age. However, we obtained evidence
that the cholinergic dependency of early SC activity reflects a presynaptic
facilitation of GABA and glutamate synaptic release via nicotinic AChRs. Our
study demonstrates that, even in its earliest form, the activity of spinal MNs
relies on a refined poly-synaptic network and involves a tight presynaptic
cholinergic regulation of both GABAergic and glutamatergic inputs.
DOI: 10.1523/JNEUROSCI.2664-13.2014
PMID: 24790209 [Indexed for MEDLINE]