Ras GTPase-activating proteins control neuronal circuit development in barrel cortex layer 4

Madhura S Rao; Hiromi Mizuno; Takuji Iwasato; Hidenobu Mizuno

doi:10.3389/fnins.2022.901774

Ras GTPase-activating proteins control neuronal circuit development in barrel cortex layer 4

Front Neurosci. 2022 Sep 16:16:901774. doi: 10.3389/fnins.2022.901774. eCollection 2022.

Authors

Madhura S Rao^{1

2}, Hiromi Mizuno^{1

2}, Takuji Iwasato^{3

4}, Hidenobu Mizuno^{1

2}

Affiliations

¹ Laboratory of Multi-Dimensional Imaging, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan.
² Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
³ Laboratory of Mammalian Neural Circuits, National Institute of Genetics, Mishima, Japan.
⁴ Department of Genetics, SOKENDAI The Graduate University for Advanced Studies, Mishima, Japan.

Abstract

The cerebral cortex comprises a complex and exquisite network of neuronal circuits that is formed during development. To explore the molecular mechanisms involved in cortical circuit formation, the tactile somatosensory pathway that connects the whiskers and cortex of rodents is a useful model. Here, we analyzed the roles of Ras GTPase-activating proteins (RasGAPs) in the circuit formation in the somatosensory cortex layer 4 (L4). We suppressed the function of RasGAPs in L4 neurons using Supernova RNAi, a plasmid vector-based sparse cell gene knockdown (KD) system. The results showed disrupted dendritic pattern formation of L4 spiny stellate neurons on the barrel edge by RasGAP KD. Furthermore, the number of presynaptic boutons on L4 neurons was reduced by RasGAP KD. These results demonstrate the essential roles of RasGAPs in circuit formation in the cerebral cortex and imply that developmental changes in dendrites and synapses in RasGAP KD neurons may be related to cognitive disabilities in RasGAP-deficient individuals, such as patients with neurofibromatosis type 1.

Keywords: RasGAP; cerebral cortex; layer 4; neonates; sparse-cell labeling; thalamocortical axons.