813B Poster - 13. Neural development and physiology
Friday April 08, 2:00 PM - 4:00 PM
Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development in Drosophila
Authors: Justin Rosenthal 1,2; Jun Yin 1; Jimmy Lei 1; Anupama Sathyamurthy 1; Jacob Short 1; Caixia Long 1; Emma Spillman 3; Chengyu Sheng 1; Quan Yuan 1
Affiliations: 1) National Institutes of Health, Bethesda, MD; 2) University of Maryland-College Park, College Park, MD; 3) University of California-San Diego, San Diego, CA
Keywords: b. dendrites; e. synaptic function and organization
The construction and maturation of the postsynaptic apparatus are crucial for synapse and dendrite development. The fundamental mechanisms underlying these processes are most often studied in glutamatergic central synapses in vertebrates. Whether the same principles apply to excitatory cholinergic synapses, such as those found in the insect central nervous system, is not known. To address this question, we investigated a group of projection neurons in the Drosophila larval visual system, the ventral lateral neurons (LNvs), and identified Dα1 and Dα6 as the main functional nicotinic acetylcholine receptor (nAchR) subunits in the larval LNvs. Using morphological analyses and calcium imaging studies, we demonstrated critical roles of these two subunits in supporting dendrite morphogenesis and synaptic transmission. Furthermore, our developmental expression profiling and endogenous tagging approaches identified distinct transcriptional controls over the two subunits resulting in the up-regulation of Dα1, which is suppressed by elevated presynaptic activity, and down-regulation of Dα6 during larval development. Additional functional analyses of synapse formation and dendrite dynamics further revealed a close association between the temporal regulation of these two nAchR subunits and their sequential requirements during cholinergic synapse maturation. Finally, preliminary screens have identified candidate regulatory factors coordinating nAchR expression and postsynaptic activity, including the transcription factor and activity-regulated gene Hr38 as well as the nAchR-specific molecular chaperone NACHO. Together, our findings highlight how transcriptional control of nAchR subunits is a core element of developmental and activity-dependent regulation of central cholinergic synapses, which is likely dependent on both transcriptional and post-translational processes.