Dissecting Molecular and Circuit Mechanisms for Inhibition and Delayed Response of ASI Neurons during Nociceptive Stimulus
Min Guo,
Minghai Ge,
Michael A. Berberoglu,
Jie Zhou,
Long Ma,
Juan Yang,
Qiyan Dong,
Yanni Feng,
Zhengxing Wu,
Zhiqiang Dong
Affiliations
Min Guo
Bio-Medical Center, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
Minghai Ge
Key Laboratory of Molecular Biophysics of Ministry of Education, Institute of Biophysics and Biochemistry, and Department of Biophysics and Molecular Physiology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Michael A. Berberoglu
Bio-Medical Center, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
Jie Zhou
Bio-Medical Center, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
Long Ma
Bio-Medical Center, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
Juan Yang
Bio-Medical Center, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
Qiyan Dong
Bio-Medical Center, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
Yanni Feng
Bio-Medical Center, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China
Zhengxing Wu
Key Laboratory of Molecular Biophysics of Ministry of Education, Institute of Biophysics and Biochemistry, and Department of Biophysics and Molecular Physiology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Zhiqiang Dong
Bio-Medical Center, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Corresponding author
Summary: The mechanisms by which off-response neurons stay quiescent during stimulation are largely unknown. Here, we dissect underlying molecular and circuit mechanisms for the inhibition of off-response ASI neurons during nociceptive Cu2+ stimulation. ASIs are inhibited in parallel by sensory neurons ASER, ADFs, and ASHs. ASER activates RIC interneurons that release octopamine (OA) to inhibit ASIs through SER-3 and SER-6 receptors. ADFs release 5-HT that acts on the SER-1 receptor to activate RICs and subsequently inhibit ASIs. Furthermore, it is an inherent property of ASIs that only a delayed on response is evoked by Cu2+ stimulation even when all inhibitory neurons are silenced. Ectopic expression of the ion channel OCR-2, which functions synergistically with OSM-9, in the cilia of ASIs can induce an immediate on response of ASIs upon Cu2+ stimulation. Our findings elucidate the molecular and circuit mechanisms regulating fundamental properties of ASIs, including their inhibition and delayed response. : Guo et al. examine a nociceptive circuit in C. elegans and show that inhibitory neurons release octopamine that inhibits ASIs via ser-3 and ser-6 receptors. ASIs show intrinsic delay in response to Cu2+ stimulation even after removal of inhibition, which can be eliminated by ectopic OCR-2 expression. Keywords: off response, ASI, neural circuits, calcium imaging, optogenetics, Caenorhabditis elegans
