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The Journal of Neuroscience, September 15, 2001, 21(18):7171-7181

Novel and Transient Populations of Corticotropin-Releasing Hormone-Expressing Neurons in Developing Hippocampus Suggest Unique Functional Roles: A Quantitative Spatiotemporal Analysis

Yuncai Chen¹, Roland A. Bender¹, Michael Frotscher², and Tallie Z. Baram¹

¹ Departments of Anatomy/Neurobiology and Pediatrics, University of California at Irvine, Irvine, California 92697-4475, and ²  Institute of Anatomy, University of Freiburg, D-79104 Freiburg, Germany

Robust physiological actions of the neuropeptide corticotropin-releasing hormone (CRH) on hippocampal pyramidal neurons have been demonstrated, which may contribute to synaptic efficacy and to learning and memory processes. These excitatory actions of the peptide, as well as the expression of the CRH receptor type that mediates them, are particularly prominent during early postnatal life, suggesting that endogenous CRH may contribute to processes involved in maturation of hippocampal circuitry. To further elucidate the function(s) of endogenous CRH in developing hippocampus, we used neurochemical and quantitative stereological methods to characterize in detail CRH-expressing neuronal populations during postnatal hippocampal differentiation. These experiments revealed progressively increasing numbers of CRH-expressing neurons in developing hippocampus that peaked on postnatal day 11-18 and then declined drastically to adult levels. These cells belonged to several discrete populations, distinguished by GAD67 mRNA expression, morphology, and distinct spatiotemporal distribution profiles. Importantly, a novel population of Cajal-Retzius-like CRH-expressing neurons was characterized that exists only transiently in early postnatal hippocampus and is positioned to contribute to the establishment of hippocampal connectivity. These findings suggest novel, age-specific roles for CRH in regulating early developmental events in the hippocampal formation.

Key words: hippocampus; dentate gyrus; Cajal-Retzius cells; GAD; interneurons; neuropeptide; development; corticotropin releasing hormone; CRF

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21187171-11$05.00/0

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