Inhibitory GABA (γ-aminobutyric acid)-ergic interneurons are a vital component of the neocortex responsible for shaping its output through a variety of inhibitions. Consisting of many flavors, interneuron subtypes are predominantly defined by their morphological, physiological, and neurochemical properties that help to determine their functional role within the neocortex. During development, these cells are born in the subpallium where they then tangentially migrate over long distances before being radially positioned to their final location in the cortical laminae. As development progresses into adolescence, these cells mature and form chemical and electrical connections with both glutamatergic excitatory neurons and other interneurons ultimately establishing the cortical network. The production, migration, and organization of these cells are determined by vast array of extrinsic and intrinsic factors that work in concert in order to assemble a proper functioning cortical inhibitory network. Failure of these cells to undergo these processes results in abnormal positioning and cortical function. In humans, this can bring about several neurological disorders including schizophrenia, epilepsy, and autism spectrum disorders. In this article, we will review previous literature that has revealed the framework for interneuron neurogenesis and migratory behavior as well as discuss recent findings that aim to elucidate the spatial and functional organization of interneurons within the neocortex.

The neocortex plays a key role in higher-order brain functions, such as perception, language and decision-making. Since the groundbreaking work of Ramón y Cajal over a century ago, defining the neural circuits underlying brain functions has been a field of intense study. Here, we review recent findings on the formation of neocortical circuits, which have taken advantage of improvements to mouse genetics and circuit-mapping tools. These findings are beginning to reveal how individual components of circuits are generated and assembled during development, and how early developmental processes, such as neurogenesis and neuronal migration, guide precise circuit assembly. Key words: Lineage, Neuronal circuits, Neocortex IntroductionThe mammalian cerebral cortex is composed of the archicortex (hippocampal region), the paleocortex (olfactory cortex) and the neocortex, with the last being the evolutionarily youngest region. The neocortex is composed of two major classes of neurons: glutamatergic projection neurons (see Glossary, Box 1), which elicit excitation in postsynaptic neurons and generate circuit output; and GABA (γ-aminobutyric acid)-ergic interneurons (see Glossary, Box 1), which typically trigger inhibition in postsynaptic neurons and are essential for shaping circuit output. It is generally accepted that two defining structural and functional features of the neocortex are lamination and radial columns (Douglas and Martin, 2004). Together, these features provide the basic framework on which neocortical circuits are built. Interestingly, both of these features are tightly linked to early developmental events, including neurogenesis and neuronal migration. In this Review, we discuss recent findings on the generation, migration and organization of excitatory and inhibitory neurons in the neocortex, with a focus on how the lineage history of neurons influences the assembly of functional circuits. Lamination: a hallmark of the neocortexThe neocortex is a continuous six-layered structure. All components of neocortical circuits, including afferents, excitatory cells, inhibitory cells and efferents, are organized with respect to the laminae (Douglas and Martin, 2004). Cortical lamination is generated as a result of radial migration of newborn excitatory neurons during development (Hatten, 1999;Rakic, 1971;Rakic, 1972). Glutamatergic excitatory neurons are produced from progenitor cells (Fig. 1A) that reside in the proliferative zone of the dorsal telencephalon (see Glossary, Box 1). In the earliest stages, the neural tube is composed of a single layer of neuroepithelial (NE) cells that proliferate rapidly (Breunig et al., 2011). A small fraction of NE cells undergoes asymmetric division to generate the first wave of postmitotic neurons, which migrate out radially and form a transient structure called the preplate (see Glossary, Box 1) (Del Río et al., 2000;Marin-Padilla, 1970;Marin-Padilla, 1971;Marin-Padilla, 1978). As development proceeds, NE cells transform into a more fate-restricted progenitor type: radial glial ...

First described by Ramon y Cajal as 'short-axon' cells over a century ago, inhibitory interneurons in the cerebral cortex make up ~20-30% of the neuronal milieu. A key feature of these interneurons is the striking structural and functional diversity, which allows them to modulate neural activity in diverse ways and ultimately endow neural circuits with remarkable computational power. Here, we 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, and how these aspects influence interneuron diversity and organization. WIREs Dev Biol 2018, 7:e306. doi: 10.1002/wdev.306 This article is categorized under: Nervous System Development > Vertebrates: General Principles.