Deficiency in transmitter release triggers homeostatic transcriptional changes that increase presynaptic excitability

C Caroline A. Cypranowska (Department of Molecular and Cell Biology, University of California Berkeley) M Maya Feldthouse (Helen Wills Neuroscience Institute, University of California Berkeley) Y Yoon Gi Choi (Functional Genomics Laboratory, University of California Berkeley) D Dariya Bakshinska (Helen Wills Neuroscience Institute, University of California Berkeley) R Rachel Li (Department of Molecular and Cell Biology, University of California Berkeley) Z Zachary L. Newman (Department of Molecular and Cell Biology, University of California Berkeley) E Ehud Y. Isacoff (Department of Molecular and Cell Biology, University of California Berkeley)

Abstract

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.

Article Details

Volume / Issue Vol. 122, Issue 31
Published August 05, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (7)

C

Caroline A. Cypranowska

Department of Molecular and Cell Biology, University of California Berkeley

M

Maya Feldthouse

Helen Wills Neuroscience Institute, University of California Berkeley

Y

Yoon Gi Choi

Functional Genomics Laboratory, University of California Berkeley

D

Dariya Bakshinska

Helen Wills Neuroscience Institute, University of California Berkeley

R

Rachel Li

Department of Molecular and Cell Biology, University of California Berkeley

Z

Zachary L. Newman

Department of Molecular and Cell Biology, University of California Berkeley

E

Ehud Y. Isacoff

Department of Molecular and Cell Biology, University of California Berkeley