TY - JOUR
T1 - Mechanisms Underlying Target Selectivity for Cell Types and Subcellular Domains in Developing Neocortical Circuits
AU - Gutman-Wei, Alan Y.
AU - Brown, Solange P.
N1 - Funding Information:
The authors thank Seong Yeol An, Kenji Johnson, Su-Jeong Kim, and Alina Spiegel for comments on the manuscript.
Funding Information:
SB was supported by the National Institutes of Health (R01 NS085121 and RF1 MH121539), the National Science Foundation (NSF 1656592), and a Klingenstein-Simons Fellowship in the Neurosciences. AG-W was supported by the National Science Foundation Graduate Research Fellowship Program.
Publisher Copyright:
© Copyright © 2021 Gutman-Wei and Brown.
PY - 2021/9/24
Y1 - 2021/9/24
N2 - The cerebral cortex contains numerous neuronal cell types, distinguished by their molecular identity as well as their electrophysiological and morphological properties. Cortical function is reliant on stereotyped patterns of synaptic connectivity and synaptic function among these neuron types, but how these patterns are established during development remains poorly understood. Selective targeting not only of different cell types but also of distinct postsynaptic neuronal domains occurs in many brain circuits and is directed by multiple mechanisms. These mechanisms include the regulation of axonal and dendritic guidance and fine-scale morphogenesis of pre- and postsynaptic processes, lineage relationships, activity dependent mechanisms and intercellular molecular determinants such as transmembrane and secreted molecules, many of which have also been implicated in neurodevelopmental disorders. However, many studies of synaptic targeting have focused on circuits in which neuronal processes target different lamina, such that cell-type-biased connectivity may be confounded with mechanisms of laminar specificity. In the cerebral cortex, each cortical layer contains cell bodies and processes from intermingled neuronal cell types, an arrangement that presents a challenge for the development of target-selective synapse formation. Here, we address progress and future directions in the study of cell-type-biased synaptic targeting in the cerebral cortex. We highlight challenges to identifying developmental mechanisms generating stereotyped patterns of intracortical connectivity, recent developments in uncovering the determinants of synaptic target selection during cortical synapse formation, and current gaps in the understanding of cortical synapse specificity.
AB - The cerebral cortex contains numerous neuronal cell types, distinguished by their molecular identity as well as their electrophysiological and morphological properties. Cortical function is reliant on stereotyped patterns of synaptic connectivity and synaptic function among these neuron types, but how these patterns are established during development remains poorly understood. Selective targeting not only of different cell types but also of distinct postsynaptic neuronal domains occurs in many brain circuits and is directed by multiple mechanisms. These mechanisms include the regulation of axonal and dendritic guidance and fine-scale morphogenesis of pre- and postsynaptic processes, lineage relationships, activity dependent mechanisms and intercellular molecular determinants such as transmembrane and secreted molecules, many of which have also been implicated in neurodevelopmental disorders. However, many studies of synaptic targeting have focused on circuits in which neuronal processes target different lamina, such that cell-type-biased connectivity may be confounded with mechanisms of laminar specificity. In the cerebral cortex, each cortical layer contains cell bodies and processes from intermingled neuronal cell types, an arrangement that presents a challenge for the development of target-selective synapse formation. Here, we address progress and future directions in the study of cell-type-biased synaptic targeting in the cerebral cortex. We highlight challenges to identifying developmental mechanisms generating stereotyped patterns of intracortical connectivity, recent developments in uncovering the determinants of synaptic target selection during cortical synapse formation, and current gaps in the understanding of cortical synapse specificity.
KW - cell-type specificity
KW - development
KW - inhibitory interneuron
KW - neocortex
KW - pyramidal cell
KW - synapse formation
KW - targeting
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U2 - 10.3389/fncir.2021.728832
DO - 10.3389/fncir.2021.728832
M3 - Review article
C2 - 34630048
AN - SCOPUS:85116927810
SN - 1662-5110
VL - 15
JO - Frontiers in Neural Circuits
JF - Frontiers in Neural Circuits
M1 - 728832
ER -