Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex

TY - JOUR

T1 - Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex

AU - Denaxa, Myrto

AU - Neves, Guilherme

AU - Rabinowitz, Adam

AU - Kemlo, Sarah

AU - Liodis, Petros

AU - Burrone, Juan

AU - Pachnis, Vassilis

PY - 2018/2/13

Y1 - 2018/2/13

N2 - 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. 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.

AB - 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. 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.

KW - activity-dependent plasticity

KW - cortical interneurons

KW - DREADS

KW - homeostatic plasticity

KW - interneuron cell death

KW - interneuron development

KW - interneuron transplantations

KW - Lhx6

UR - http://www.scopus.com/inward/record.url?scp=85041994600&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.01.064

DO - 10.1016/j.celrep.2018.01.064

M3 - Article

AN - SCOPUS:85041994600

SN - 2211-1247

VL - 22

SP - 1710

EP - 1721

JO - Cell Reports

JF - Cell Reports

IS - 7

ER -