Behavioral resilience via dynamic circuit firing homeostasis

• 成果类型: Article
• 署名作者: Hoagland, Adam; Schultz, Ryan; Cai, Zerong; Newman, Zachary L.; Isacoff, Ehud Y.
• 署名单位: University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Minnesota System; University of Minnesota Twin Cities
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12704
• DOI: 10.1073/pnas.2421386122
• 发表日期: 2025-05-06
• 关键词: synaptic-transmission; nervous-system; drosophila; transmitter; mechanisms; COMPENSATION; expression; plasticity; release; neurons

摘要

Homeostatic regulation ensures stable neural circuit output under changing conditions. We find that in Drosophila larvae, either presynaptic weakening due to perturbation of transmitter release or postsynaptic weakening due to perturbation of glutamate receptors at synapses between motor neuron (MN) and muscle has little impact on locomotion, suggesting a nonsynaptic compensatory mechanism. In vivo imaging shows that five different forms of synaptic weakening increase the duration of activity bouts in type I MNs. Strikingly, this compensation is input selective: occurring only in the tonic type Ib MN, not the phasic type Is MN that innervates the same muscle. Moreover, an inhibitory class of central pre-MNs that innervates the tonic-but not phasic-input decreases in activity. The adjustment in activity occurs remarkably quickly: within minutes of synapse perturbation. We propose that MN firing is dynamically regulated by two coordinated mechanisms: a cell-autonomous adjustment of MN excitability and a circuit adjustment of inhibitory central drive. The input selectivity of this process suggests homeostatic adjustment to maintain tonic drive but hold constant the phasic drive that organizes locomotory wave patterns.