Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex
Myrto Denaxa,
Guilherme Neves,
Adam Rabinowitz,
Sarah Kemlo,
Petros Liodis,
Juan Burrone,
Vassilis Pachnis
Affiliations
Myrto Denaxa
Nervous System Development and Homeostasis Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Corresponding author
Guilherme Neves
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; Corresponding author
Adam Rabinowitz
Bioinformatics and Biostatistics Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Sarah Kemlo
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
Petros Liodis
Molecular Neurobiology, National Institute for Medical Research, the Ridgeway, Mill Hill, London NW7 1AA, UK
Juan Burrone
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; Corresponding author
Vassilis Pachnis
Nervous System Development and Homeostasis Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Corresponding author
Summary: 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.