Synapse- specific catecholaminergic modulation of neuronal glutamate release

• 成果类型: Article
• 署名作者: Bakshinska, Dariya; Liu, William YuChen; Schultz, Ryan; Stowers, R. Steven; Hoagland, Adam; Cypranowska, Caroline; Stanley, Cherise; Younger, Susan H.; Newman, Zachary L.; Isacoff, Ehud Y.
• 署名单位: Francis Crick Institute; University of Minnesota System; University of Minnesota Twin Cities; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Montana State University System; Montana State University Bozeman; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11299
• DOI: 10.1073/pnas.2420496121
• 发表日期: 2025-01-07
• 关键词: drosophila; octopamine; transmission; receptor; RECRUITMENT; activation; plasticity; vesicles; munc13-1; muscles

摘要

Norepinephrine in vertebrates and its invertebrate analog, octopamine, regulate the activity of neural circuits. We find that, when hungry, Drosophila larvae switch activcoincide with locomotion- driving bursts in type I glutamatergic MNs that converge on the same muscles. Optical quantal analysis across hundreds of synapses simultaneously reveals that octopamine potentiates glutamate release by tonic type Ib MNs, but not phasic type Is MNs, and occurs via the Gq- coupled octopamine receptor (OAMB). OAMB is more abundant in type Ib terminals and acts through diacylglycerol and its target Unc13A, a key component of the glutamate release machinery. Potentiation varies significantly-by up to 1,000%-across synapses of a single Ib axon, with synaptic Unc13A levels determining both release probability and potentiation. We propose that a dual molecular mechanism-an upstream neuromodulator receptor and a downstream tonic synapses exhibit large potentiation, while weaker tonic and all phasic synapses maintain consistency, yielding a sophisticated regulation of locomotor behavior.