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Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex
Myrto Denaxa1, Guilherme Neves2, Adam Rabinowitz3
1Nervous System Development and Homeostasis Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Cell Reports
|February 15, 2018
Summary
Cortical interneuron (CI) numbers are adjusted by programmed cell death. Neuronal activity levels can reduce CI apoptosis, suggesting a homeostatic mechanism for balancing brain networks.
Area of Science:
- Neuroscience
- Developmental biology
- Computational neuroscience
Background:
- Cortical networks rely on a balance between excitatory and inhibitory neurons.
- The precise mechanisms establishing the number of cortical interneurons (CIs) in the mammalian forebrain remain unclear.
- CIs are generated in excess and undergo apoptosis during early postnatal development to regulate their final numbers.
Purpose of the Study:
- To investigate the factors influencing the programmed cell death of CIs.
- To determine if neuronal activity affects CI numbers.
- To explore the potential for homeostatic regulation of CI populations.
Main Methods:
- Utilized a mouse model to study CI development.
- Manipulated neuronal activity during the critical postnatal window.
- Assessed the extent of CI apoptosis using cell-type specific markers and imaging techniques.
Main Results:
- The degree of CI apoptosis is not fixed but is plastic and cell-type specific.
- Acute increases in neuronal activity can reduce CI apoptosis in a cell-autonomous manner.
- This suggests that neuronal activity plays a role in regulating CI numbers.
Conclusions:
- The number of CIs is dynamically regulated by activity-dependent apoptosis.
- Emerging neural network activity influences local CI populations to maintain homeostatic balance.
- This provides insight into the developmental mechanisms ensuring proper cortical function.
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