Targeted manipulation of neuronal activity in behaving adult flies

Abstract

The ability to control the activity of specific neurons in freely behaving animals provides an effective way to probe the contributions of neural circuits to behavior. Wide interest in studying principles of neural circuit function using the fruit fly Drosophila melanogaster has fueled the construction of an extensive transgenic toolkit for performing such neural manipulations. Here we describe approaches for using these tools to manipulate the activity of specific neurons and assess how those manipulations impact the behavior of flies. We also describe methods for examining connectivity among multiple neurons that together form a neural circuit controlling a specific behavior. This work provides a resource ABSTRACTThe ability to control the activity of specific neurons in freely behaving animals provides an effective way to probe the contributions of neural circuits to behavior. Wide interest in studying principles of neural circuit function using the fruit fly Drosophila melanogaster has fueled the construction of an extensive transgenic toolkit for performing such neural manipulations. Here we describe approaches for using these tools to manipulate the activity of specific neurons and assess how those manipulations impact the behavior of flies. We also describe methods for examining connectivity among multiple neurons that together form a neural circuit controlling a specific behavior. This work provides a resource for researchers interested in examining how neurons and neural circuits contribute to the rich repertoire of behaviors performed by flies.

Tools for Rapid High-Resolution Behavioral Phenotyping of Automatically Isolated Drosophila

“…Beyond identifying behavioral algorithms, FlyPEZ, used in conjunction with the Drosophila genetic toolkit, provides a platform to interrogate their neural implementation. FlyPEZ can be used to conduct high-throughput behavior screens with collections of flies having any one of a variety of genetic manipulations, including RNAi (Gibson et al, 2015), enhancer-traps (White and Peabody, 2009), null mutants (Takahashi et al, 2008), and GAL4 (Hampel and Seeds, 2017;Jenett et al, 2012;Tirian and Dickson, 2017) or split-GAL4 (Aso et al, 2014;Cande et al, 2017;Wu et al, 2016) collections. As an example, we used FlyPEZ to identify distinct roles for different visual projection neuron cell types in the coordination of the looming escape response.…”

The Drosophila Split Gal4 System for Neural Circuit Mapping

“…Methods for temperature-mediated neuronal activation followed, as did the explosive development of “optogenetic” tools for light-mediated neuronal activation and inactivation (Bernstein et al, 2012 ). Today, the toolkit of effector transgenes available to neurobiologists to manipulate and monitor neuronal function in flies and other genetic model organisms make Crick’s original request seem somewhat quaint (Hampel and Seeds, 2017 ; Martin and Alcorta, 2017 ; Luo et al, 2018 ). Although it remains an aspirational goal to be able to selectively target the expression of such transgenes to each individual neuronal cell type in an animal, advances in genetic targeting techniques are placing even this goal within reach.…”