Constructing and Tuning Excitatory Cholinergic Synapses: The Multifaceted Functions of Nicotinic Acetylcholine Receptors in Drosophila Neural Development and Physiology

Abstract

Nicotinic acetylcholine receptors (nAchRs) are widely distributed within the nervous system across most animal species. Besides their well-established roles in mammalian neuromuscular junctions, studies using invertebrate models have also proven fruitful in revealing the function of nAchRs in the central nervous system. During the earlier years, both in vitro and animal studies had helped clarify the basic molecular features of the members of the Drosophila nAchR gene family and illustrated their utility as targets for insecticides. Later, increasingly sophisticated techniques have illuminated how nAchRs mediate excitatory neurotransmission in the Drosophila brain and play an integral part in neural development and synaptic plasticity, as well as cognitive processes such as learning and memory. This review is intended to provide an updated survey of Drosophila nAchR subunits, focusing on their molecular diversity and unique contributions to physiology and plasticity of the fly neural circuitry. We will also highlight promising new avenues for nAchR research that will likely contribute to better understanding of central cholinergic neurotransmission in both Drosophila and other organisms.

Single-cell transcriptome profiles of Drosophila fruitless-expressing neurons from both sexes

“…We find nicotinic acetylcholine receptor (nAChR) subunits are marker genes for the majority of clusters in the full data set (91 clusters out of 113) ( Source data 3 ). Nicotinic acetylcholine receptor are pentameric receptors that assemble with combinations of 10 subunits [seven α nAChR subunits (1–7) and three β nAChR subunits (1–3)] ( Rosenthal and Yuan, 2021 ). Of these 10 nAChR subunit genes, we find that nine are marker genes and all 10 are expressed in the full data set ( Source data 3 ).…”

Planning and Implementing Strategically

“…Other examples, drawn from the NINDS Division of Intramural Research, are the finding that the microbiome contributes to the features of normal aging 6 and studies aimed at understanding how experience and genetic programming interact to shape structural and functional connectivity during brain development. 7,8 NINDS also issued a Request for Applications through the BRAIN Initiative entitled, “New Technologies and Novel Approaches for Recording and Modulation in the Nervous System,” to develop the tools we will need to better document and analyze electrical signaling in the normal nervous system.…”

Single-cell transcriptome profiles ofDrosophila fruitless-expressing neurons from both sexes

“…We find nicotinic acetylcholine receptor (nAChR) subunits are marker genes for the majority of clusters in the full data set (91 clusters out of 113) ( Supplemental Table 4 ). Nicotinic acetylcholine receptor are pentameric receptors that assemble with combinations of 10 subunits [seven α nAChR subunits (1-7) and three β nAChR subunits (1-3)] (Rosenthal and Yuan, 2021). Of these 10 nAChR subunit genes, we find that nine are marker genes and all 10 are expressed in the full data set ( Supplemental Table 4).…”