Spontaneous network activity in the embryonic spinal cord regulates AMPAergic and GABAergic synaptic strength.
Spontaneous network activity (SNA) has been described in most developing circuits, including the spinal cord, retina, and hippocampus. Despite the widespread nature of this developmental phenomenon, its role in network maturation is poorly understood. We reduced SNA in the intact embryo and found compensatory increases in synaptic strength of spinal motoneuron inputs. AMPAergic miniature postsynaptic current (mPSC) amplitude and frequency increased following the reduction of activity. Interestingly, excitatory GABAergic mPSCs also increase in amplitude through a process of synaptic scaling. Finally, the normal modulation of GABAergic mPSC amplitude was accelerated. Together, these compensatory responses appear to increase the excitability of the cord and could act to maintain appropriate SNA levels, thus demonstrating a distinct functional role for synaptic homeostasis. Because spontaneous network activity can regulate AMPAergic and GABAergic synaptic strength during development, SNA is likely to play an important role in a coordinated maturation of excitatory and inhibitory synaptic strength.
Department of Physiology, Emory University, School of Medicine, Atlanta, Georgia 30322, USA.
Carlos
C
Gonzalez-Islas
Peter
P
Wenner
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002642:Chick Embryo; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008012:Lidocaine; D001640:Bicuculline