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Cell Rep. 2018 Feb 13;22(7):1710-1721. doi: 10.1016/j.celrep.2018.01.064.

Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex.

Author information

1
Nervous System Development and Homeostasis Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: denaxa@fleming.gr.
2
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK. Electronic address: guilherme.neves@kcl.ac.uk.
3
Bioinformatics and Biostatistics Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
4
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK.
5
Molecular Neurobiology, National Institute for Medical Research, the Ridgeway, Mill Hill, London NW7 1AA, UK.
6
Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, London SE1 1UL, UK. Electronic address: juan.burrone@kcl.ac.uk.
7
Nervous System Development and Homeostasis Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: vassilis.pachnis@crick.ac.uk.

Abstract

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.

KEYWORDS:

DREADS; Lhx6; activity-dependent plasticity; cortical interneurons; homeostatic plasticity; interneuron cell death; interneuron development; interneuron transplantations

PMID:
29444425
PMCID:
PMC6230259
DOI:
10.1016/j.celrep.2018.01.064
[Indexed for MEDLINE]
Free PMC Article

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