@article {69633, title = {A Drosophila computational brain model reveals sensorimotor processing.}, journal = {Nature}, volume = {634}, year = {2024}, month = {2024 Oct 02}, pages = {210-219}, abstract = {

The recent assembly of the adult Drosophila melanogaster central brain connectome, containing more than 125,000 neurons and 50 million synaptic connections, provides a template for examining sensory processing throughout the brain. Here we create a leaky integrate-and-fire computational model of the entire Drosophila brain, on the basis of neural connectivity and neurotransmitter identity, to study circuit properties of feeding and grooming behaviours. We show that activation of sugar-sensing or water-sensing gustatory neurons in the computational model accurately predicts neurons that respond to tastes and are required for feeding initiation. In addition, using the model to activate neurons in the feeding region of the Drosophila brain predicts those that elicit motor neuron firing-a testable hypothesis that we validate by optogenetic activation and behavioural studies. Activating different classes of gustatory neurons in the model makes accurate predictions of how several taste modalities interact, providing circuit-level insight into aversive and appetitive taste processing. Additionally, we applied this model to mechanosensory circuits and found that computational activation of mechanosensory neurons predicts activation of a small set of neurons comprising the antennal grooming circuit, and accurately describes the circuit response upon activation of different mechanosensory subtypes. Our results demonstrate that modelling brain circuits using only synapse-level connectivity and predicted neurotransmitter identity generates experimentally testable hypotheses and can describe complete sensorimotor transformations.

}, keywords = {Animals, Brain, Computer Simulation, Connectome, Drosophila melanogaster, Feeding Behavior, Female, Grooming, Male, Models, Neurological, Motor Neurons, Optogenetics, Synapses, Taste}, issn = {1476-4687}, doi = {10.1038/s41586-024-07763-9}, url = {https://doi.org/10.1038/s41586-024-07763-9}, author = {Shiu, Philip K and Sterne, Gabriella R and Spiller, Nico and Franconville, Romain and Sandoval, Andrea and Zhou, Joie and Simha, Neha and Kang, Chan Hyuk and Yu, Seongbong and Kim, Jinseop S and Dorkenwald, Sven and Matsliah, Arie and Schlegel, Philipp and Yu, Szi-Chieh and McKellar, Claire E and Sterling, Amy and Costa, Marta and Eichler, Katharina and Bates, Alexander Shakeel and Eckstein, Nils and Funke, Jan and Jefferis, Gregory S X E and Murthy, Mala and Bidaye, Salil S and Hampel, Stefanie and Seeds, Andrew M and Scott, Kristin} } @article {48788, title = {Simultaneous activation of parallel sensory pathways promotes a grooming sequence in Drosophila.}, journal = {eLife}, volume = {6}, year = {2017}, month = {2017 Sep 09}, abstract = {

A central model that describes how behavioral sequences are produced features a neural architecture that readies different movements simultaneously, and a mechanism where prioritized suppression between the movements determines their sequential performance. We previously described a model whereby suppression drives a Drosophila grooming sequence that is induced by simultaneous activation of different sensory pathways that each elicit a distinct movement (Seeds et al. 2014). Here, we confirm this model using transgenic expression to identify and optogenetically activate sensory neurons that elicit specific grooming movements. Simultaneous activation of different sensory pathways elicits a grooming sequence that resembles the naturally induced sequence. Moreover, the sequence proceeds after the sensory excitation is terminated, indicating that a persistent trace of this excitation induces the next grooming movement once the previous one is performed. This reveals a mechanism whereby parallel sensory inputs can be integrated and stored to elicit a delayed and sequential grooming response.

}, issn = {2050-084X}, doi = {10.7554/eLife.28804}, author = {Hampel, Stefanie and McKellar, Claire E and Simpson, Julie H and Seeds, Andrew M} } @inbook {47793, title = {Targeted manipulation of neuronal activity in behaving adult flies.}, booktitle = {Decoding Neural Circuit Structure and Function}, year = {2017}, month = {2016 Aug 15}, pages = {191-222}, 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 for researchers interested in examining how neurons and neural circuits contribute to the rich repertoire of behaviors performed by flies.

}, doi = {10.1007/978-3-319-57363-2_7}, author = {Hampel, Stefanie and Seeds, Andrew M} } @article {47038, title = {A neural command circuit for grooming movement control.}, journal = {eLife}, volume = {4}, year = {2015}, month = {2015 Sep 7}, abstract = {

Animals perform many stereotyped movements, but how nervous systems are organized for controlling specific movements remains unclear. Here we use anatomical, optogenetic, behavioral, and physiological techniques to identify a circuit in Drosophila melanogaster that can elicit stereotyped leg movements that groom the antennae. Mechanosensory chordotonal neurons detect displacements of the antennae and excite three different classes of functionally connected interneurons, which include two classes of brain interneurons and different parallel descending neurons. This multilayered circuit is organized such that neurons within each layer are sufficient to specifically elicit antennal grooming. However, we find differences in the durations of antennal grooming elicited by neurons in the different layers, suggesting that the circuit is organized to both command antennal grooming and control its duration. As similar features underlie stimulus-induced movements in other animals, we infer the possibility of a common circuit organization for movement control that can be dissected in Drosophila.

}, issn = {2050-084X}, doi = {10.7554/eLife.08758}, author = {Hampel, Stefanie and Franconville, Romain and Simpson, Julie H and Seeds, Andrew M} } @article {45417, title = {A suppression hierarchy among competing motor programs drives sequential grooming in Drosophila.}, journal = {eLife}, volume = {3}, year = {2014}, month = {2014 Aug 19}, pages = {e02951}, abstract = {

Motor sequences are formed through the serial execution of different movements, but how nervous systems implement this process remains largely unknown. We determined the organizational principles governing how dirty fruit flies groom their bodies with sequential movements. Using genetically targeted activation of neural subsets, we drove distinct motor programs that clean individual body parts. This enabled competition experiments revealing that the motor programs are organized into a suppression hierarchy; motor programs that occur first suppress those that occur later. Cleaning one body part reduces the sensory drive to its motor program, which relieves suppression of the next movement, allowing the grooming sequence to progress down the hierarchy. A model featuring independently evoked cleaning movements activated in parallel, but selected serially through hierarchical suppression, was successful in reproducing the grooming sequence. This provides the first example of an innate motor sequence implemented by the prevailing model for generating human action sequences.

}, issn = {2050-084X}, doi = {10.7554/eLife.02951}, author = {Seeds, Andrew M and Ravbar, Primoz and Chung, Phuong and Hampel, Stefanie and Midgley, Frank M and Mensh, Brett D and Simpson, Julie H} } @article {1513, title = {Drosophila brainbow: a recombinase-based fluorescence labeling technique to subdivide neural expression patterns.}, journal = {Nature Methods}, volume = {8}, year = {2011}, month = {2011 Mar}, pages = {253-9}, abstract = {

We developed a multicolor neuron labeling technique in Drosophila melanogaster that combines the power to specifically target different neural populations with the label diversity provided by stochastic color choice. This adaptation of vertebrate Brainbow uses recombination to select one of three epitope-tagged proteins detectable by immunofluorescence. Two copies of this construct yield six bright, separable colors. We used Drosophila Brainbow to study the innervation patterns of multiple antennal lobe projection neuron lineages in the same preparation and to observe the relative trajectories of individual aminergic neurons. Nerve bundles, and even individual neurites hundreds of micrometers long, can be followed with definitive color labeling. We traced motor neurons in the subesophageal ganglion and correlated them to neuromuscular junctions to identify their specific proboscis muscle targets. The ability to independently visualize multiple lineage or neuron projections in the same preparation greatly advances the goal of mapping how neurons connect into circuits.

}, issn = {1548-7105}, doi = {10.1038/nmeth.1566}, author = {Hampel, Stefanie and Chung, Phuong and McKellar, Claire E and Hall, Donald and Looger, Loren L and Simpson, Julie H} }