Life Science

Generation of Diverse Cortical Inhibitory Interneurons

Our current understanding of the generation of cortical interneurons with a focus on recent efforts to bridge the gap between progenitor behavior and interneuron production is reviewed.

The brain is the center of all our thoughts, feelings, and actions. The fundamental building blocks of this complex organ are billions of neurons, interconnected with each other via trillions of synapses. A defining characteristic of a neuron is its ability to communicate with other neurons through electrochemical signals. Excitatory neurons and inhibitory interneurons, act as the accelerator and the brake, respectively, in the flow of electrochemical information in the brain.

In the mammalian cerebral cortex, a majority of neurons (~70-80%) are excitatory; the remaining neurons (~20-30%) consist of an exuberant array of inhibitory interneurons critical for regulating brain activity. Since their discovery over a century ago, the remarkable plethora of interneuron subtypes have been extensively characterized along various criteria. Notably, a greater diversity of interneuron subtypes in higher mammals such as human and non-human primates is thought to underlie the increased complexity of cortical function and enhanced cognitive abilities in these species. Generation of the correct numbers and subtypes of interneurons is critical in maintaining the fine balance between excitation and inhibition.

During development, inhibitory interneurons are generated by highly specialized stem cells called radial glial progenitor cells (RGPs) that reside in transient regions of the ventral forebrain. After birth, they undergo a long journey to reach their destination in the overlying cortex.

RGPs are a pivotal cell type in the developing brain, as they not only serve as the stem cells to generate the correct numbers of neurons, they also provide a migration scaffold to guide the newly born neurons to their final location in the brain. Whereas significant progress has been made in the field of excitatory neurogenesis, our understanding of how interneuron neurogenesis, and more specifically, how progenitor behavior influences the generation of interneuron diversity in the cortex, has lagged.

How do the developmental origins control the production of the appropriate numbers and diversity of interneurons critical for proper brain function? In an advanced review, Sultan and Shi review our current understanding of the generation of cortical interneurons with a focus on recent efforts to bridge the gap between progenitor behavior and interneuron production.

 

Kindly contributed by Khadeejah Sultan.

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