Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development in Drosophila

Rosenthal, JS and Yin, J and Lei, J and Sathyamurthy, A and Short, J and Long, C and Spillman, E and Sheng, C and Yuan, Q (2021) Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development in Drosophila. In: Proceedings of the National Academy of Sciences of the United States of America, 118 (23).

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Abstract

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 nAchRα1 (Dα1) and nAchRα6 (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 RNA sequencing analyses and endogenous tagging approach identified distinct transcriptional controls over the two subunits in the LNvs, which led to the up-regulation of Dα1 and down-regulation of Dα6 during larval development as well as to an activity-dependent suppression of Dα1. Additional functional analyses of synapse formation and dendrite dynamics further revealed a close association between the temporal regulation of individual nAchR subunits and their sequential requirements during the cholinergic synapse maturation. Together, our findings support transcriptional control of nAchR subunits as a core element of developmental and activity-dependent regulation of central cholinergic synapses. © 2021 National Academy of Sciences. All rights reserved.

Item Type:	Journal Article
Publication:	Proceedings of the National Academy of Sciences of the United States of America
Publisher:	National Academy of Sciences
Additional Information:	The copyright for this article belongs to National Academy of Sciences
Department/Centre:	Division of Biological Sciences > Centre for Neuroscience
Date Deposited:	26 Aug 2021 09:51
Last Modified:	26 Aug 2021 09:51
URI:	http://eprints.iisc.ac.in/id/eprint/69318

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