Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex.

Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex.
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DOI:
10.1016/j.celrep.2018.01.064
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发表时间:
2018-02-13
期刊:
影响因子:
8.8
通讯作者:
Pachnis V
Pachnis V
中科院分区:
生物学1区
文献类型:
--
作者:
Denaxa M;Neves G;Rabinowitz A;Kemlo S;Liodis P;Burrone J;Pachnis V

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Cortical networks are composed of excitatory projection neurons and inhibitory interneurons. Finding the right balance between the two is important for controlling overall cortical excitation and network dynamics. However, it is unclear how the correct number of cortical interneurons (CIs) is established in the mammalian forebrain. CIs are generated in excess from basal forebrain progenitors, and their final numbers are adjusted via an intrinsically determined program of apoptosis that takes place during an early postnatal window. Here, we provide evidence that the extent of CI apoptosis during this critical period is plastic and cell-type specific and can be reduced in a cell-autonomous manner by acute increases in neuronal activity. We propose that the physiological state of the emerging neural network controls the activity levels of local CIs to modulate their numbers in a homeostatic manner. Lhx6 is required for survival of CIs generated in the MGE MGE-derived CI loss is compensated for by a decrease in CGE-derived interneuron apoptosis Increases in cortical network activity are correlated with improved CI survival Transient, cell-autonomous depolarization improves the survival of grafted CIs Denaxa et al. address how the number of interneurons in the cortex is regulated. They show that apoptosis of developing interneurons can be modulated by activity in the forebrain of young mice so that increases in activity can rescue interneurons from apoptosis. This feedback loop provides a mechanism for fine-tuning the number and repertoire of interneurons in the brain.
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