Publication Date:
2012-10-09
Description:
Cortical inhibitory circuits are formed by gamma-aminobutyric acid (GABA)-secreting interneurons, a cell population that originates far from the cerebral cortex in the embryonic ventral forebrain. Given their distant developmental origins, it is intriguing how the number of cortical interneurons is ultimately determined. One possibility, suggested by the neurotrophic hypothesis, is that cortical interneurons are overproduced, and then after their migration into cortex the excess interneurons are eliminated through a competition for extrinsically derived trophic signals. Here we characterize the developmental cell death of mouse cortical interneurons in vivo, in vitro and after transplantation. We found that 40% of developing cortical interneurons were eliminated through Bax (Bcl-2-associated X)-dependent apoptosis during postnatal life. When cultured in vitro or transplanted into the cortex, interneuron precursors died at a cellular age similar to that at which endogenous interneurons died during normal development. Over transplant sizes that varied 200-fold, a constant fraction of the transplanted population underwent cell death. The death of transplanted neurons was not affected by the cell-autonomous disruption of TrkB (tropomyosin kinase receptor B), the main neurotrophin receptor expressed by neurons of the central nervous system. Transplantation expanded the cortical interneuron population by up to 35%, but the frequency of inhibitory synaptic events did not scale with the number of transplanted interneurons. Taken together, our findings indicate that interneuron cell death is determined intrinsically, either cell-autonomously or through a population-autonomous competition for survival signals derived from other interneurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726009/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726009/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Southwell, Derek G -- Paredes, Mercedes F -- Galvao, Rui P -- Jones, Daniel L -- Froemke, Robert C -- Sebe, Joy Y -- Alfaro-Cervello, Clara -- Tang, Yunshuo -- Garcia-Verdugo, Jose M -- Rubenstein, John L -- Baraban, Scott C -- Alvarez-Buylla, Arturo -- F32NS061497/NS/NINDS NIH HHS/ -- R01 NS048528/NS/NINDS NIH HHS/ -- R01 NS071785/NS/NINDS NIH HHS/ -- T32 GM007618/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Nov 1;491(7422):109-13. doi: 10.1038/nature11523. Epub 2012 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neuroscience Graduate Program, University of California, San Francisco, California 94143, USA. dereksouthwell@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23041929" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Animals, Newborn
;
*Apoptosis
;
Caspase 3/metabolism
;
Cell Aging/physiology
;
Cell Count
;
Cell Survival
;
Female
;
Inhibitory Postsynaptic Potentials
;
Interneurons/*cytology/metabolism/transplantation
;
Male
;
Membrane Glycoproteins/deficiency/genetics/metabolism
;
Mice
;
Mice, Inbred C57BL
;
Neocortex/*cytology/growth & development
;
Neural Stem Cells/cytology/metabolism/transplantation
;
Protein-Tyrosine Kinases/deficiency/genetics/metabolism
;
Pyramidal Cells/cytology/metabolism
;
bcl-2-Associated X Protein/deficiency/genetics/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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