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Notch and NGF/p75 NTR control dendrite morphology and the balance of excitatory/inhibitory synaptic input to hippocampal neurones through Neurogenin 3
Author(s) -
SalamaCohen Patricia,
Arévalo MaríaÁngeles,
Grantyn Rosemarie,
RodríguezTébar Alfredo
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03783.x
Subject(s) - inhibitory postsynaptic potential , dendrite (mathematics) , synaptogenesis , excitatory postsynaptic potential , biology , microbiology and biotechnology , hippocampal formation , neuroscience , geometry , mathematics
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 p75 NTR , 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/p75 NTR 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 p75 NTR 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/p75 NTR to dendritic and synaptic plasticity through Neurogenin 3 signalling.