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Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration

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

Madhura S Rao^1,2, Hiromi Mizuno^1,2, Takuji Iwasato^3,4

¹Laboratory of Multi-Dimensional Imaging, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan.

Frontiers in Neuroscience

|October 3, 2022

Summary

Ras GTPase-activating proteins (RasGAPs) are crucial for forming neuronal circuits in the rodent somatosensory cortex. Suppressing RasGAPs disrupted dendritic patterns and reduced presynaptic boutons in layer 4 neurons.

Keywords:

RasGAP cerebral cortex layer 4 neonates sparse-cell labeling thalamocortical axons

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Published on: January 10, 2015

Area of Science:

Neuroscience
Developmental Biology
Molecular Biology

Background:

The cerebral cortex develops intricate neuronal circuits.
Rodent whisker-to-cortex pathways model cortical circuit formation.
Ras GTPase-activating proteins (RasGAPs) are implicated in neural development.

Purpose of the Study:

To investigate the role of RasGAPs in somatosensory cortex layer 4 (L4) circuit formation.
To understand molecular mechanisms underlying cortical development.

Main Methods:

Utilized a plasmid vector-based sparse cell gene knockdown (KD) system (Supernova RNAi).
Suppressed RasGAP function in L4 neurons of the rodent somatosensory cortex.

Main Results:

RasGAP KD led to disrupted dendritic pattern formation in L4 spiny stellate neurons.
A reduction in the number of presynaptic boutons on L4 neurons was observed after RasGAP KD.

Conclusions:

RasGAPs play essential roles in cerebral cortex circuit formation.
Altered dendrite and synapse development in RasGAP KD neurons may link to cognitive deficits in RasGAP-deficient individuals, including those with neurofibromatosis type 1.