Modulation of apoptosis controls inhibitory interneuron number in the cortex

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, 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. Note: Equal contribution and authors for correspondence: Vassilis.Pachnis@crick.ac.uk and juan.burrone@kcl.ac.uk Note: Equal contribution and co-first authors: Myrto Denaxa and Guilherme Neves