QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 25, 2008, 28(26):6720-6730; doi:10.1523/JNEUROSCI.1677-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bhattacharyya, B. J. Articles by Miller, R. J. PubMed PubMed Citation Articles by Bhattacharyya, B. J. Articles by Miller, R. J.

 Previous Article  |  Next Article 

Cellular/Molecular
The Chemokine Stromal Cell-Derived Factor-1 Regulates GABAergic Inputs to Neural Progenitors in the Postnatal Dentate Gyrus

Bula J. Bhattacharyya,¹ Ghazal Banisadr,¹ Hosung Jung,¹ Dongjun Ren,¹ Darran G. Cronshaw,² Yongrui Zou,² and Richard J. Miller¹

¹Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and ²Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032

Correspondence should be addressed to Richard J. Miller, Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611. Email: r-miller10{at}northwestern.edu

Stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) are important regulators of the development of the dentate gyrus (DG). Both SDF-1 and CXCR4 are also highly expressed in the adult DG. We observed that CXCR4 receptors were expressed by dividing neural progenitor cells located in the subgranular zone (SGZ) as well as their derivatives including doublecortin-expressing neuroblasts and immature granule cells. SDF-1 was located in DG neurons and in endothelial cells associated with DG blood vessels. SDF-1-expressing neurons included parvalbumin-containing GABAergic interneurons known as basket cells. Using transgenic mice expressing an SDF-1-mRFP1 (monomeric red fluorescence protein 1) fusion protein we observed that SDF-1 was localized in synaptic vesicles in the terminals of basket cells together with GABA-containing vesicles. These terminals were often observed to be in close proximity to dividing nestin-expressing neural progenitors in the SGZ. Electrophysiological recordings from slices of the DG demonstrated that neural progenitors received both tonic and phasic GABAergic inputs and that SDF-1 enhanced GABAergic transmission, probably by a postsynaptic mechanism. We also demonstrated that, like GABA, SDF-1 was tonically released in the DG and that GABAergic transmission was partially dependent on coreleased SDF-1. These data demonstrate that SDF-1 plays a novel role as a neurotransmitter in the DG and regulates the strength of GABAergic inputs to the pool of dividing neural progenitors. Hence, SDF-1/CXCR4 signaling is likely to be an important regulator of adult neurogenesis in the DG.

Key words: cytokine; dentate gyrus; GABA; hippocampus; neurogenesis; transgenic; SDF-1/CXCL12; CXCR4

---

Received Feb. 4, 2008; revised May 13, 2008; accepted May 15, 2008.

Correspondence should be addressed to Richard J. Miller, Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611. Email: r-miller10{at}northwestern.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help