Notch and NGF/p75NTR control dendrite morphology and the balance of excitatory/inhibitory synaptic input to hippocampal neurones through Neurogenin 3

J Neurochem. 2006 Jun;97(5):1269-78. doi: 10.1111/j.1471-4159.2006.03783.x. Epub 2006 Mar 15.


We have previously shown that dendrite morphology of cultured hippocampal neurones is controlled by Notch receptor activation or binding of nerve growth factor (NGF) to its low affinity receptor p75NTR, i.e. processes that up-regulate the expression of the Homologue of enhancer of split 1 and 5. Thus, the increased expression of these genes decreases the number of dendrites, whereas abrogation of Homologue of enhancer of split 1/5 activity stimulates the outgrowth of new dendrites. Here, we show that Neurogenin 3 is a proneural gene that is negatively regulated by Homologue of enhancer of split 1/5. It also influences dendrite morphology. Hence, a deficit of Notch or NGF/p75NTR activation can lead to the production of high levels of Neurogenin 3, which stimulates the outgrowth of new dendrites. Conversely, activation of either Notch or p75NTR depressed Neurogenin 3 expression, which not only decreased the number of dendrites but also favoured inhibitory (GABAergic) synaptogenesis, thereby diminishing the ratios of excitatory/inhibitory inputs. NGF also augmented the levels of mRNA encoding the vesicular inhibitory amino acid transporter, but it did not affect the fraction of GAD65/67-positive neurones. Conversely, overexpression of Neurogenin 3 largely reduced the number of inhibitory synaptic contacts and, consequently, produced a strong increase in the ratios of excitatory/inhibitory synaptic terminals. Our results reveal a hitherto unknown contribution of NGF/p75NTR to dendritic and synaptic plasticity through Neurogenin 3 signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Dendrites / metabolism*
  • Dendrites / ultrastructure
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Plasma Membrane Transport Proteins / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Hippocampus / cytology
  • Hippocampus / embryology*
  • Hippocampus / metabolism
  • Homeodomain Proteins / metabolism
  • Mice
  • Nerve Growth Factor / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Neural Inhibition / physiology
  • Neural Pathways / cytology
  • Neural Pathways / embryology
  • Neural Pathways / metabolism
  • Neuronal Plasticity / physiology
  • Receptor, Nerve Growth Factor / metabolism*
  • Receptor, Notch1 / metabolism*
  • Synapses / metabolism*
  • Synapses / ultrastructure
  • Synaptic Transmission / physiology
  • Transcription Factor HES-1
  • Up-Regulation / physiology
  • gamma-Aminobutyric Acid / metabolism


  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • GABA Plasma Membrane Transport Proteins
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Notch1 protein, mouse
  • Receptor, Nerve Growth Factor
  • Receptor, Notch1
  • Transcription Factor HES-1
  • gamma-Aminobutyric Acid
  • Nerve Growth Factor