preprints.org > biology > other > doi: 10.20944/preprints202203.0268.v1

Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 17 March 2022 / Approved: 18 March 2022 / Online: 18 March 2022 (11:54:51 CET)

A key goal of modern neuroscience involves understanding how connections in the brain form and function. Such a knowledge is essential to better inform how defects in the exquisitely complex steps of nervous system growth underlie neuropsychiatric and neurodevelopmental disorders. In the last 40 years, studies of the nervous system in the fruit fly Drosophila melanogaster enabled the discovery of a wealth of molecular and genetic mechanisms that drive the development of these synaptic connections – specialized cell-to-cell connections that are the essential substrate for information flow and processing in the nervous system. The major driver of knowledge focused on studies at the neuromuscular junction due to its ease of examination. Analogous studies in the central nervous system lagged behind due to a lack of genetic accessibility of specific central neuron classes, appropriate synaptic labels compatible with cell-type specific access, and high resolution, quantitative imaging strategies. However, understanding how synapses in central circuits form remains a prerequisite to understanding brain development. In the last decade, a host of new tools and techniques made possible the extension of genetic studies of synapse organization into central circuits and greatly enhanced our understanding of central synapse formation, organization, and maturation. In this review, we consider the current state-of-the-field, focusing on two major elements. We first discuss the tools, technologies, and strategies developed to visualize and quantify synapses in vivo in genetically identifiable neurons of the Drosophila CNS. Second, we explore in depth how these tools enabled a clearer understanding of synaptic development and organization in different circuits of the fly brain and discovered novel molecular mechanisms that underlie synapse formation. These studies establish multiple brain regions in the fly as powerful in vivo genetic models that offer novel insights into synaptogenic regulators and mechanisms of neural development.

synapse; central nervous system; drosophila; synaptogenesis; genetics; development; active zones

BIOLOGY, Other