Ca2+ excitability of glia to neuromodulator octopamine in Drosophila living brain is greater than that of neurons

Abstract

Aim

Octopamine in the Drosophila brain has a neuromodulatory role similar to that of noradrenaline in mammals. After release from Tdc2 neurons, octopamine/tyramine may trigger intracellular Ca²⁺ signaling via adrenoceptor-like receptors on neural cells, modulating neurotransmission. Octopamine/tyramine receptors are expressed in neurons and glia, but how each of these cell types responds to octopamine remains elusive. This study aimed to characterize Ca²⁺ responses of neurons and astrocytes to neuromodulatory octopamine signals.

Methods

We expressed Ca²⁺ indicator jGCaMP7b in specific cell type in adult Drosophila brains and performed intracellular Ca²⁺ imaging in the brain optic lobes upon bath application of octopamine by confocal microscopy.

Results

Octopamine-stimulated Ca²⁺ responses in neurons were different from those of glial cells. The amplitude of octopamine-mediated Ca²⁺ signals in neurons was 3.4-fold greater than in astrocytes. However, astrocytes were more sensitive to octopamine; the median effective concentration that triggered Ca²⁺ responses was nearly 6-fold lower in astrocytes than in neurons. In both cell types, Ca²⁺ transients are shaped by G_q and G_s protein-coupled octopamine/tyramine receptors. Our snRNA-seq database screening uncovered differential expression patterns of these receptors between brain cell types, which may explain the difference in Ca²⁺ signaling.

Conclusion

In the brain optic lobes, astrocytes, not neurons, appear to be the sole responders to low concentration octopamine signals, and therefore likely drive synaptic plasticity and visual processing. Given the interconnectivity of the optic lobes with other brain regions, octopaminergic signals acting through the optic lobe astrocytes may also influence higher-order brain functions including learning and memory.