transplantation-chemogenetically-engineered-cortical-interneuron

Transplantation of Chemogenetically Engineered Cortical Interneuron Progenitors into Early Postnatal Mouse Brains

Neuronal development is regulated by a complex combination of environmental and genetic factors. Assessing the relative contribution of each component is ...

King's College London

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.

Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex.

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 , 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.

Article	Year
Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex. Cell reports\| PubMed ID: 29444425	2018
Homeostatic Regulation of Interneuron Apoptosis During Cortical Development. Journal of experimental neuroscience\| PubMed ID: 30013387	2018

Guilherme Neves

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