Modulation of dendritic differentiation by corticotropin-releasing factor in the developing hippocampus

Yuncai Chen, Roland A. Bender, Kristen L. Brunson, Jörn K. Pomper, Dimitri E. Grigoriadis, Wolfgang Wurst, Tallie Z. Baram

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155 Scopus citations


The interplay of environmental and genetic factors in the developmental organization of the hippocampus has not been fully elucidated. The neuropeptide corticotropin-releasing factor (CRF) is released from hippocampal interneurons by environmental signals, including stress, to increase synaptic efficacy. In the early postnatal hippocampus, we have previously characterized a transient population of CRF-expressing Cajal-Retzius-like cells. Here we queried whether this stress-activated neuromodulator influences connectivity in the developing hippocampal network. Using mice deficient in the principal hippocampal CRF receptor [CRF 1(-/-)] and organotypic cultures grown in the presence of synthetic CRF, or CRF receptor antagonists, we found robust effects of CRF on dendritic differentiation in hippocampal neurons. In CRF 1(-/-) mice, the dendritic trees of hippocampal principal cells were exuberant, an effect that was induced in normal hippocampi in vitro by the presence of CRF 1 antagonists. In both cases, total dendritic length and dendritic branching were significantly increased. In contrast, exogenous synthetic CRF blunted the dendritic growth in hippocampal organotypic cultures. Taken together, these findings suggest that endogenous CRF, if released excessively by previous early postnatal stress, might influence neuronal connectivity and thus function of the immature hippocampus.

Original languageEnglish
Pages (from-to)15782-15787
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number44
StatePublished - 2 Nov 2004
Externally publishedYes


  • Cajal-retzius cells
  • Corticotropin-releasing factor receptor
  • Corticotropin-releasing hormone
  • Neuropeptide
  • Stress


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