NSF Award
2420655
ABSTRACT<br/><br/>Nervous systems are biological communication networks that use signaling molecules called neurotransmitters to transfer information critical to every facet of brain function. “Bilingual” neurons are neurons that release two types of neurotransmitters to communicate with other neurons. Co-transmission allows the brain to fine-tune responses with multiple messages, which increases the functional flexibility of the brain, allowing it to accurately respond to a continually changing environment appropriately. The increasing number of examples of “bilingual” neurons found in the brains of animals from flies to humans indicates this is a fundamental mechanism by which neurons communicate. Despite this functional significance, there is still only limited insight into how co-transmission is regulated within neurons, and how the social environment impacts neuron communication. In this proposal, the investigators will use the fruit fly, Drosophila, to identify mechanisms that regulate co-transmission and identify how these mechanisms are dynamically regulated by the animal’s social environment, in both females and males. The outcomes of this work include an in-depth understanding of how multiple neurotransmitters generate behavioral flexibility, and separately provide a potential neuroprotective role in response to a social isolation environment. The project will provide research experience to students in diverse molecular and physiological techniques through international training and mentoring. In addition, each investigator will engage historically excluded groups in science at the University of Montana, Brown University, and Bar-Ilan University.<br/><br/>In this proposal, the investigators will leverage their deep understanding of behavior-promoting neurons, spatial transcriptomic approaches, and functional imaging to test the hypothesis that the molecular and physiological mechanisms that regulate co-transmission are themselves dynamically regulated by sex and state-dependent properties. The PIs will use cutting-edge techniques to examine how glutamate+/octopamine+ neurons in the Drosophila model system differ within a novel sex-specific context as well in response to state-dependent changes at the anatomical, transcriptomic and functional level. Specifically, the investigators will first address how the neural dynamics, neurotransmitter levels and distribution of glutamate and octopamine are impacted in the context of sexual dimorphism and the social isolation state. Second, they will identify transcriptional pathways that regulate glutamate or octopamine signaling through single nuclei RNA-seq and the spatial transcriptomics technology, Ex-seq. Laboratory settings are increasingly international and collaborative places, both in the university and in the global biotechnology industry. As a team the investigators are providing a collaborative and interactive training plan for their students to receive international instruction and mentoring, as well as learn new molecular and physiological techniques. Additional student education will occur through laboratory courses taught at Brown University and the University of Montana. Ultimately, this work will fill a large gap in our understanding of the regulation of co-transmission by identifying the rich assortment of communication capabilities that neurons possess in behaving animals.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
