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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 21, 2007, 27(47):12787-12796; doi:10.1523/JNEUROSCI.3302-07.2007

This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lin, P.-Y. Articles by Birren, S. J. Search for Related Content PubMed PubMed Citation Articles by Lin, P.-Y. Articles by Birren, S. J.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Non-Cell-Autonomous Regulation of GABAergic Neuron Development by Neurotrophins and the p75 Receptor

Pao-Yen Lin,^1,2 * Jeanine M. Hinterneder,^1 * Sarah R. Rollor,¹ and Susan J. Birren¹

¹Department of Biology, Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, and ²Department of Psychiatry, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, County 831, Taiwan

Correspondence should be addressed to Dr. Susan J. Birren, Department of Biology, Brandeis University, MS 008, 415 South Street, Waltham, MA 02454. Email: birren{at}brandeis.edu

Basal forebrain GABAergic and cholinergic circuits regulate the activity of cholinergic projections to the cortex and hippocampus. Because these projections influence cortical development and function, the development of basal forebrain excitatory and inhibitory neurons is critical for overall brain development. We show that the neurotransmitter phenotype of these neurons is developmentally regulated by neurotrophins and the p75 receptor. Neurotrophins (nerve growth factor and brain-derived neurotrophic factor) increased the number of both cholinergic and GABAergic neurons in neonatal basal forebrain neuron cultures from the region of the medial septum. However, the p75 receptor is required only for neurotrophin-dependent expansion of the GABAergic, not the cholinergic, population. Neurotrophin-induced GABAergic development can be rescued in p75^–/– cultures by expression of a p75 rescue construct in neighboring cells or by treatment with medium collected from neurotrophin-treated wild-type cultures. Because p75 is not expressed in basal forebrain GABAergic neurons, this defines a new, non-cell-autonomous mechanism of p75 action in which ligand binding results in release of a soluble factor that modifies neurotrophin responses of nearby neurons. p75 is also required for the maintenance of basal forebrain GABAergic neurons in vivo, demonstrating that p75-mediated interactions between cholinergic and GABAergic neurons regulate the balance of excitatory and inhibitory components of basal forebrain circuits.

Key words: basal forebrain; neurotransmitter phenotype; neurotrophins; p75 receptor; cholinergic neurons; GABAergic neurons

---

Received July 20, 2007; revised Sept. 26, 2007; accepted Oct. 17, 2007.

Correspondence should be addressed to Dr. Susan J. Birren, Department of Biology, Brandeis University, MS 008, 415 South Street, Waltham, MA 02454. Email: birren{at}brandeis.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help