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Transplantation of Chemogenetically Engineered Cortical Interneuron Progenitors into Early Postnatal Mouse Brains
Published on: August 26, 2019
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Intrinsically determined cell death of developing cortical interneurons.
Derek G Southwell1, Mercedes F Paredes, Rui P Galvao
1Neuroscience Graduate Program, University of California, San Francisco, California 94143, USA. dereksouthwell@gmail.com
Nature
|October 9, 2012
Summary
Cortical interneuron numbers are determined by intrinsic factors, not external signals. About 40% of these γ-aminobutyric acid (GABA)-secreting neurons undergo programmed cell death during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Cortical inhibitory circuits rely on γ-aminobutyric acid (GABA)-secreting interneurons originating from the ventral forebrain.
- The mechanisms determining the final number of cortical interneurons, despite their distant developmental origins, remain unclear.
- The neurotrophic hypothesis suggests overproduction and subsequent elimination via competition for external trophic signals.
Purpose of the Study:
- To investigate the developmental cell death of mouse cortical interneurons.
- To determine whether interneuron survival is regulated by extrinsic trophic factors or intrinsic mechanisms.
- To explore the role of Bax and TrkB in interneuron survival and population regulation.
Main Methods:
- In vivo and in vitro studies of mouse cortical interneuron development.
- Transplantation experiments to assess survival and cell death under varying conditions.
- Analysis of Bax-dependent apoptosis and TrkB signaling pathways.
Main Results:
- Approximately 40% of developing cortical interneurons undergo Bax-dependent apoptosis postnatally.
- Interneuron precursors transplanted into the cortex or cultured in vitro exhibited cell death at developmentally similar times.
- Cell death rates were constant across a 200-fold range of transplant sizes and unaffected by TrkB disruption.
- Transplantation increased interneuron numbers but did not proportionally increase inhibitory synaptic event frequency.
Conclusions:
- Cortical interneuron cell death appears to be determined intrinsically, either cell-autonomously or via population-level competition among interneurons.
- Extrinsic trophic signals do not seem to be the primary regulators of interneuron survival.
- The findings challenge the traditional neurotrophic hypothesis for interneuron population control.
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