Molecular logic of neocortical projection neuron specification, development and diversity

Abstract

The sophisticated circuitry of the neocortex is assembled from a diverse repertoire of neuronal subtypes generated during development under precise molecular regulation. In recent years, several key controls over the specification and differentiation of neocortical projection neurons have been identified. This work provides substantial insight into the “molecular logic” underlying cortical development, increasingly supporting a model in which individual progenitor-stage and postmitotic regulators are embedded within highly-interconnected networks that gate sequential developmental decisions. Here, we provide an integrative account of the molecular controls that direct the progressive development and delineation of subtype and area identity of neocortical projection neurons.

Synapse-type-specific plasticity in local circuits

“…At L2/3 visual cortical neurons, L4 synapses undergo a reduction in short-term depression through development, but at intralaminar L2/3 synapses onto the same postsynaptic cell type do not undergo this change [27,31 •• ,32 •• ,33]. These layer-specific differences in STP may result from different developmental time points for layer formation [34], and therefore these differences may not always last into adulthood.…”

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…The plethora of cell types in the adult brain arise from progenitor pools in distinct subregions of the developing brain that are established as early as the morphogenic patterning of the neural tube (Bystron et al, 2008;Marin and Rubenstein, 2003). Progenitors in the subventricular zone that produce projection neurons express diverse combinations of transcription factors that guide them from proliferation through differentiation into unique types of cells (Greig et al, 2013;Molyneaux et al, 2007). Similarly, GABAergic interneuron types are predetermined based on unique transcription factor combinations in different progenitor types in the subpallial ganglionic eminences (Flames et al, 2007;Wonders and Anderson, 2006).…”

Selective Manipulation of Neural Circuits

“…Specific circuits can be targeted based on their connectivity rather than genetic identity [13,14]. As shown in Fig.…”

“…A similar transcriptional profile helps to determine function during maturity [10,11,13,14]. Therefore, these cell type-specific genes are attractive targets to manipulate specific types of neurons.…”