Activity-dependent homeostatic specification of transmitter expression in embryonic neurons

Nature. 2004 Jun 3;429(6991):523-30. doi: 10.1038/nature02518.


Neurotransmitters are essential for interneuronal signalling, and the specification of appropriate transmitters in differentiating neurons has been related to intrinsic neuronal identity and to extrinsic signalling proteins. Here we show that altering the distinct patterns of Ca2+ spike activity spontaneously generated by different classes of embryonic spinal neurons in vivo changes the transmitter that neurons express without affecting the expression of markers of cell identity. Regulation seems to be homeostatic: suppression of activity leads to an increased number of neurons expressing excitatory transmitters and a decreased number of neurons expressing inhibitory transmitters; the reverse occurs when activity is enhanced. The imposition of specific spike frequencies in vitro does not affect labels of cell identity but again specifies the expression of transmitters that are inappropriate for the markers they express, during an early critical period. The results identify a new role of patterned activity in development of the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Calcium / metabolism
  • Calcium Signaling
  • Cell Differentiation
  • Cells, Cultured
  • Gene Expression Regulation*
  • Homeostasis*
  • Humans
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology*
  • Neurotransmitter Agents / metabolism*
  • Organ Specificity
  • Phenotype
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Rats
  • Sodium Channels / genetics
  • Sodium Channels / metabolism
  • Spinal Cord / cytology*
  • Spinal Cord / embryology*
  • Spinal Cord / metabolism
  • Xenopus laevis


  • Neurotransmitter Agents
  • Potassium Channels, Inwardly Rectifying
  • Sodium Channels
  • Calcium