Metaplasticity governs natural experience-driven plasticity of nascent embryonic brain circuits

Neuron. 2009 Oct 29;64(2):240-50. doi: 10.1016/j.neuron.2009.08.034.


During embryogenesis, brain neurons receiving the same sensory input may undergo potentiation or depression. While the origin of variable plasticity in vivo is unknown, it plays a key role in shaping dynamic neural circuit refinement. Here, we investigate effects of natural visual stimuli on neuronal firing within the intact, awake, developing brain using calcium imaging of 100 s of central neurons in the Xenopus retinotectal system. We find that specific patterns of visual stimuli shift population responses toward either potentiation or depression in an N-methyl-D-aspartate receptor (NMDA-R)-dependent manner. In agreement with Bienenstock-Cooper-Munro metaplasticity, our results show that functional potentiation or depression can be predicted by individual neurons' specific receptive field properties and historic firing rates. Interestingly, this activity-dependent metaplasticity is itself NMDA-R dependent. Furthermore, network analysis reveals increased correlated firing of neurons that undergo potentiation. These findings implicate metaplasticity as a natural property regulating experience-dependent refinement of nascent embryonic brain circuits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Action Potentials / physiology
  • Animals
  • Behavior, Animal
  • Biophysics
  • Brain / anatomy & histology*
  • Brain / embryology
  • Calcium / metabolism
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Models, Neurological*
  • Nerve Net / cytology*
  • Nerve Net / embryology*
  • Neurons / drug effects
  • Neurons / physiology
  • Photic Stimulation / methods
  • Statistics as Topic
  • Superior Colliculi / cytology
  • Superior Colliculi / embryology
  • Synapses / physiology
  • Visual Pathways / physiology
  • Xenopus laevis


  • Excitatory Amino Acid Antagonists
  • 2-Amino-5-phosphonovalerate
  • Calcium