Changes in presynaptic gene expression during homeostatic compensation at a central synapse

Abstract

Homeostatic matching of pre-and postsynaptic function has been observed in many species and neural structures, but whether transcriptional changes contribute to this form of trans-synaptic coordination remains unknown. To identify genes whose expression is altered in presynaptic neurons as a result of perturbing postsynaptic excitability, we applied a transcriptomics-friendly, temperature-inducible Kir2.1-based activity clamp at the first synaptic relay of the Drosophila olfactory system, a central synapse known to exhibit trans-synaptic homeostatic matching. Twelve hours after adult-onset suppression of activity in postsynaptic antennal lobe projection neurons of males and females, we detected changes in the expression of many genes in the third antennal segment, which houses the somata of presynaptic olfactory receptor neurons. These changes affected genes with roles in synaptic vesicle release and synaptic remodeling, including several implicated in homeostatic plasticity at the neuromuscular junction. At 48 h and beyond, the transcriptional landscape tilted toward protein synthesis, folding, and degradation; energy metabolism; and cellular stress defenses, indicating that the system had been pushed to its homeostatic limits. Our analysis suggests that similar homeostatic machinery operates at peripheral and central synapses and identifies many of its components. The presynaptic transcriptional response to genetically targeted postsynaptic perturbations could be exploited for the construction of novel connectivity tracing tools.