NeuroD2 regulates the development of hippocampal mossy fiber synapses

Neural Dev. 2012 Feb 27;7:9. doi: 10.1186/1749-8104-7-9.

Abstract

Background: The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF) synapse.

Results: Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice.

Conclusion: These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cells, Cultured
  • Dendritic Spines / genetics*
  • Dendritic Spines / metabolism
  • Hippocampus / metabolism*
  • Mice
  • Mice, Knockout
  • Mossy Fibers, Hippocampal / metabolism*
  • Neurons / metabolism
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Synapses / genetics*
  • Synapses / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Neurod2 protein, mouse
  • Neuropeptides