Glycine release from radial cells modulates the spontaneous activity and its propagation during early spinal cord development.
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.
Scain
Anne-Laure
AL
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7102, Université Pierre et Marie Curie, F-75005 Paris, France.
Le Corronc
Hervé
H
Allain
Anne-Emilie
AE
Muller
Emilie
E
Rigo
Jean-Michel
JM
Meyrand
Pierre
P
Branchereau
Pascal
P
Legendre
Pascal
P
D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005998:Glycine / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D010507:Periodicity; D011247:Pregnancy; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D055366:Synaptic Potentials / Q000502:physiology*
D005998:Glycine