Spontaneous network activity in the embryonic spinal cord regulates AMPAergic and GABAergic synaptic strength

Neuron. 2006 Feb 16;49(4):563-75. doi: 10.1016/j.neuron.2006.01.017.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Anesthetics, Local / pharmacology
  • Animals
  • Bicuculline / pharmacology
  • Chick Embryo
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Antagonists / pharmacology
  • Lidocaine / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Nerve Net / physiology*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Inhibition / radiation effects
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / radiation effects
  • Patch-Clamp Techniques / methods
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Reaction Time / radiation effects
  • Spinal Cord / cytology
  • Spinal Cord / embryology
  • Synapses / drug effects
  • Synapses / physiology*
  • Synapses / radiation effects
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synaptic Transmission / radiation effects
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Anesthetics, Local
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • gamma-Aminobutyric Acid
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Lidocaine
  • Bicuculline