Homeostatic Regulation of Interneuron Apoptosis During Cortical Development

Abstract

The mammalian cortex consists of two main neuronal types: the principal excitatory pyramidal neurons (PNs) and the inhibitory interneurons (INs). The interplay between these two neuronal populations - which drive excitation and inhibition (E/I balance), respectively - is crucial for controlling the overall activity in the brain. A number of neurological and psychiatric disorders have been associated with changes in E/I balance. It is not surprising, therefore, that neural networks employ several different mechanisms to maintain their firing rates at a stable level, collectively referred as homeostatic forms of plasticity. Here, we share our views on how the size of IN populations may provide an early homeostatic checkpoint for controlling brain activity. In a recent paper published in Cell Reports, we demonstrate that the extent of IN apoptosis during a critical early postnatal period is plastic, cell type specific, and can be reduced in a cell-autonomous manner by acute increases in neuronal activity. We propose that a critical interplay between the physiological state of the network and its cellular units fine-tunes the size of IN populations with the aim of stabilizing network activity.

Keywords: Cortical interneurons; Lhx6 transcription factor; cell death; neuronal activity.

Figure 1.

Proposed model for an activity-dependent control of inhibitory interneuron (IN) survival. Under normal network activity levels, a constant proportion of immature cortical INs dies due to apoptosis. When network activity is increased, the fraction of INs that undergoes apoptosis is significantly reduced. The survival of INs is dependent on a cell-autonomous induction of activity-dependent pro-survival pathways. Most probably, these pathways are dependent on the function of calcium-binding phosphatase calcineurin.