Gliotransmission orchestrates neuronal type-specific axon regeneration

Abstract

Injured neurons exhibit cell type-specific axon regeneration, but the underlying mechanisms remain elusive. Two subtypes of Drosophila sensory neurons show distinct regenerative competence. Here, we show that axotomy induces long-lasting burst firing and Ca 2+ spikes specifically in the regenerative subtype. Genetic silencing of firing in the regenerative subtype inhibits regeneration. Optogenetic stimulation of the nonregenerative subtype reveals that activity patterns critically determine regeneration; burst firing triggers Ca 2+ spikes and suffices to induce regeneration, while tonic firing fails to induce Ca 2+ spikes and regeneration. We further show the L-type Ca 2+ channel, Dmca1D, regulates Ca 2+ spikes and regeneration. Intriguingly, the regenerative neuronal subtype expresses higher levels of Dmca1D, and overexpression of Dmca1D in the non-regenerative subtype facilitates regeneration. Our studies indicate that injury induces cell type-specific neuronal activities, which act through Ca 2+ spikes to govern regeneration, and suggest that precise control of neuronal activity patterns is an effective way to promote regeneration.

Dynamics of sleep and feeding homeostasis inDrosophilaglia and neurons

“…In mice, microglia generate inhibitory feedback and suppress activity of glutamatergic neurons 71 , a mechanism which could also play a role in sleep regulation in an adenosine-dependent manner 72 . Recent evidence suggests that ensheathing glia could also release adenosine with increasing calcium levels 73 . Adenosine seems however not to be important for sleep control in the fly 74 .…”