Deficiency in transmitter release triggers homeostatic transcriptional changes that increase presynaptic excitability
- Caroline A. Cypranowska
- Maya Feldthouse
- Yoon Gi Choi
- Dariya Bakshinska
- Rachel Li
- Zachary L. Newman
- Ehud Y. Isacoff
2025-07-29
Weakening of synaptic transmission at the Drosophila larval neuromuscular junction triggers two forms of homeostatic compensation, one that increases the probability of glutamate release per action potential ( P r ) and another that increases motoneuron (MN) activity. We investigated the molecular changes in MNs that underlie the increase in MN activity. RNA sequencing (RNA-seq) analysis on MNs whose glutamate release is weakened by knockdown of components of the MN transmitter release machinery reveals a reduction in expression of a group of genes that encode potassium channels and their positive modulators. These results identify a mechanism of compensation for weakened synaptic transmission by MNs, which engages a transcriptional program in those cells to increase firing and, thereby, ensure sufficient locomotory drive.