Chemogenetically induced Gq signaling is involved in the dendritic and axonal pattern formation of cortical neurons

Electrical activity plays a crucial role in the development of neurons and the formation of neuronal networks. Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools that can control the activity of neurons at the single-cell level by activating specific G protein signaling. In this study, we aimed to investigate whether the excitatory hM3Dq receptor is sufficient to influence the growth of dendrites and axons in cortical neurons. When activated, Gq-coupled hM3Dq leads to depolarization by increasing intracellular calcium levels. We biolistically transfected hM3Dq into immature cortical neurons in rat visual cortex slice cultures and activated it using clozapine-N-oxide (CNO) dissolved in water. The receptor was functionally expressed and stable in the neurons. We analyzed the neurons after stimulation in two postnatal time periods: DIV 5-10 and 10-20. Our findings revealed that Gq signaling can modulate the differentiation of apical dendrites of L2/3 pyramidal cells until DIV 10 and of apical dendrites of L5/6 pyramidal cells until DIV 20. Additionally, the growth of horizontal collaterals and bouton terminaux of pyramidal cell axons was strongly promoted by Gq signaling. We demonstrate that DREADDs are precise tools for modulating activity in single cells in a wild-type network. Our findings suggest that activity via Gq signaling plays a crucial role in the maturation of postnatal L2/3 pyramidal cells. Additionally, excitatory Gq signaling is a critical factor for the formation and rearrangement of dendritic and axonal patterns.