Glycine Release from Radial Cells Modulates the Spontaneous Activity and Its Propagation during Early Spinal Cord Development
Journal of Neuroscience. 2010-01-06; 30(1): 390-403
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1. J Neurosci. 2010 Jan 6;30(1):390-403. doi: 10.1523/JNEUROSCI.2115-09.2010.
Glycine release from radial cells modulates the spontaneous activity and its
propagation during early spinal cord development.
Scain AL(1), Le Corronc H, Allain AE, Muller E, Rigo JM, Meyrand P, Branchereau
P, Legendre P.
(1)Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7102,
Université Pierre et Marie Curie, F-75005 Paris, France.
Rhythmic electrical activity is a hallmark of the developing embryonic CNS and is
required for proper development in addition to genetic programs. Neurotransmitter
release contributes to the genesis of this activity. In the mouse spinal cord,
this rhythmic activity occurs after embryonic day 11.5 (E11.5) as waves spreading
along the entire cord. At E12.5, blocking glycine receptors alters the
propagation of the rhythmic activity, but the cellular source of the glycine
receptor agonist, the release mechanisms, and its function remain obscure. At
this early stage, the presence of synaptic activity even remains unexplored.
Using isolated embryonic spinal cord preparations and whole-cell patch-clamp
recordings of identified motoneurons, we find that the first synaptic activity
develops at E12.5 and is mainly GABAergic. Using a multiple approach including
direct measurement of neurotransmitter release (i.e., outside-out sniffer
technique), we also show that, between E12.5 and E14.5, the main source of
glycine in the embryonic spinal cord is radial cell progenitors, also known to be
involved in neuronal migration. We then demonstrate that radial cells can release
glycine during synaptogenesis. This spontaneous non-neuronal glycine release can
also be evoked by mechanical stimuli and occurs through volume-sensitive chloride
channels. Finally, we find that basal glycine release upregulates the propagating
spontaneous rhythmic activity by depolarizing immature neurons and by increasing
membrane potential fluctuations. Our data raise the question of a new role of
radial cells as secretory cells involved in the modulation of the spontaneous
electrical activity of embryonic neuronal networks.
PMID: 20053920 [Indexed for MEDLINE]