A Drosophila computational brain model reveals sensorimotor processing

• 成果类型: Article
• 署名作者: Shiu, Philip K.; Sterne, Gabriella R.; Spiller, Nico; Franconville, Romain; Sandoval, Andrea; Zhou, Joie; Simha, Neha; Kang, Chan Hyuk; Yu, Seongbong; Kim, Jinseop S.; Dorkenwald, Sven; Matsliah, Arie; Schlegel, Philipp; Yu, Szi-chieh; McKellar, Claire E.; Sterling, Amy; Costa, Marta; Eichler, Katharina; Bates, Alexander Shakeel; Eckstein, Nils; Funke, Jan; Jefferis, Gregory S. X. E.; Murthy, Mala; Bidaye, Salil S.; Hampel, Stefanie; Seeds, Andrew M.; Scott, Kristin
• 署名单位: University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Rochester; Max Planck Society; Sungkyunkwan University (SKKU); Princeton University; Princeton University; University of Cambridge; MRC Laboratory Molecular Biology; University of Oxford; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; University of Puerto Rico; University of Puerto Rico Medical Sciences Campus
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3901
• DOI: 10.1038/s41586-024-07763-9
• 发表日期: 2024-10-03
• 关键词: bitter taste; neurons; sugar; neuromodulation; REPRESENTATIONS; melanogaster; connectome; SYSTEM; sweet; pair

摘要

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(1,2). Here we create a leaky integrate-and-fire computational model of the entire Drosophila brain, on the basis of neural connectivity and neurotransmitter identity3, 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 initiation4. In addition, using the model to activate neurons in the feeding region of the Drosophila brain predicts those that elicit motor neuron firing5-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(6-10). 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.