Silencing neuronal activity is required for developmental circuit remodeling

Abstract

SummaryPostnatal refinement of neuronal connectivity shapes the mature nervous system. Pruning of exuberant connections involves both cell autonomous and non-cell autonomous mechanisms, such as neuronal activity. While the role of neuronal activity in the plasticity of excitatory synapses has been extensively studied, the involvement of inhibition is less clear. Furthermore, the role of activity during stereotypic developmental remodeling, where competition is not as apparent, is not well understood.Here we use the Drosophila mushroom body as a model to show that regulated silencing of neuronal activity is required for developmental axon pruning of the γ-Kenyon cells. We demonstrate that silencing neuronal activity is mechanistically achieved by cell autonomous expression of the inward rectifying potassium channel (irk1) combined with inhibition by the GABAergic APL neuron. These results support the Hebbian-like rule ‘use it or lose it’, where inhibition can destabilize connectivity and promote pruning while excitability stabilizes existing connections.

Orai mediated Calcium entry determines activity of central dopaminergic neurons by regulation of gene expression

“…Over the course of development, neurons define an excitability set point within a dynamic range (Truszkowski and Aizenman, 2015), which stabilizes existing connections (Mayseless et al, 2023) and enables circuit maturation (Johnson-Venkatesh et al, 2015). In this study, we identify an essential role for the storeoperated Ca 2+ channel Orai in setting the excitability threshold of a subset of dopaminergic neurons central to a MB circuit for Drosophila flight.…”

“…Over the course of development, neurons define an excitability set point within a dynamic range (Truszkowski and Aizenman, 2015), which stabilizes existing connections (Mayseless et al, 2023) and enables circuit maturation (Johnson-Venkatesh et al, 2015). The setting of this threshold for individual classes of neurons is based on the relative expression of various ion channels.…”