PRESYNAPTIC PLASTICITY AT THE <EM>DROSOPHILA</EM> NMJ IS TRANSCRIPTIONALLY REGULATED

Adaptive neural circuit function relies critically on plastic changes in synaptic strength. Spontaneous miniature excitatory potentials (mEPSPs) arise from the fusion of single synaptic vesicles with the plasma membrane, and quantal size was initially considered fixed. However, combining immunohistochemistry and electrophysiological recordings I revealed that increased locomotor activity at the Drosophila neuromuscular junction (NMJ) elevates vesicular glutamate transporter (vGlut) expression, thereby increasing quantal size and synaptic strength. This quantal size increase requires calcium influx through Cav1 voltage-gated calcium channels, as Cav1 knockdown rescues the activity-induced increase in quantal size. Calcium ions act as both charge carriers and second messengers, mediating various physiological processes including gene transcription. Thus, activity-dependent calcium influx through Cav1 likely activates calcium-dependent signaling to upregulate vGlut expression. Using the vGlut enhancer coupled to Gal4 with UAS-tdTomato confirmed transcriptional upregulation of vGlut. Thus, I have identified a novel regulatory mechanism in which activity dependent presynaptic calcium influx through Cav1 regulates vGlut transcription. Furthermore, I narrowed down the genomic site responsible for vGlut regulation by utilizing different vGlut enhancer fragments. Further bioinformatic and genetic analyses revealed that the NF-kB transcription factor relish is required for the transcriptional upregulation of vGlut. Typically, Drosophila larval motoneurons compensate for increased quantal size by activating presynaptic glutamate gated chloride channels (GluCla), which reduces quantal content to drive presynaptic homeostatic depression (PHD). However, activity and calcium influx dependent global transcriptional upregulation of vGlut does not induce PHD, because the presynaptic expression of GluCla is reduced. Consequently, synaptic transmission is enhanced without homeostatic compensation.