Functional analysis of periaqueductal gray neurons projecting to the medulla in active and passive defensive behaviors
Fear responses and defensive behaviors are essential for survival. Fear responses are mediated by neural circuits that detect threatening stimuli and classify them as “unpleasant” or “aversive”. These circuits coordinate the selection of defensive behaviors, such as freezing or flight, depending on...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
|
| Series: | Neuroscience Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0168010225001221 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849237966310866944 |
|---|---|
| author | Yuki Honshuku Yuki Yamaguchi Koki Kawazoe Yuki Nishida Yuki Kurauchi Masabumi Minami Hiroshi Katsuki Natsuko Hitora-Imamura |
| author_facet | Yuki Honshuku Yuki Yamaguchi Koki Kawazoe Yuki Nishida Yuki Kurauchi Masabumi Minami Hiroshi Katsuki Natsuko Hitora-Imamura |
| author_sort | Yuki Honshuku |
| collection | DOAJ |
| description | Fear responses and defensive behaviors are essential for survival. Fear responses are mediated by neural circuits that detect threatening stimuli and classify them as “unpleasant” or “aversive”. These circuits coordinate the selection of defensive behaviors, such as freezing or flight, depending on the perceived imminence of the threat. Activation of excitatory neurons in the lateral/ventrolateral periaqueductal gray (l/vlPAG) induces diverse fear responses, depending on the subregions, projection targets, and stimulation intensity. Some l/vlPAG neurons project to the magnocellular nucleus of the medulla (Mc). However, it remains unclear which of the diverse behaviors arising from different intensities of l/vlPAG stimulation are mediated via the l/vlPAG-Mc pathway. Additionally, the role of the l/vlPAG-Mc pathway activation in driving negative or positive valence-related behavior is unknown. To address these questions, we used optogenetics to stimulate Mc-projecting l/vlPAG neurons at two levels of light intensity and analyzed the resulting behavioral changes. Strong stimulation of Mc-projecting l/vlPAG neurons induced flight behavior, whereas weak stimulation elicited a freezing response. Real-time and conditioned place aversion tests indicated that strong stimulation was aversive. These findings suggest that strong stimulation of Mc-projecting l/vlPAG neurons induces active defensive behavior and behavioral aversion, while weak stimulation induces passive defensive behavior. |
| format | Article |
| id | doaj-art-ca633fe371bf499c9452b194aa00aabc |
| institution | Kabale University |
| issn | 0168-0102 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neuroscience Research |
| spelling | doaj-art-ca633fe371bf499c9452b194aa00aabc2025-08-20T04:01:48ZengElsevierNeuroscience Research0168-01022025-09-0121810493910.1016/j.neures.2025.104939Functional analysis of periaqueductal gray neurons projecting to the medulla in active and passive defensive behaviorsYuki Honshuku0Yuki Yamaguchi1Koki Kawazoe2Yuki Nishida3Yuki Kurauchi4Masabumi Minami5Hiroshi Katsuki6Natsuko Hitora-Imamura7Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, JapanDepartment of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, JapanDepartment of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, JapanDepartment of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, JapanDepartment of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, JapanDepartment of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, JapanDepartment of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, JapanDepartment of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Correspondence to: 5–1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.Fear responses and defensive behaviors are essential for survival. Fear responses are mediated by neural circuits that detect threatening stimuli and classify them as “unpleasant” or “aversive”. These circuits coordinate the selection of defensive behaviors, such as freezing or flight, depending on the perceived imminence of the threat. Activation of excitatory neurons in the lateral/ventrolateral periaqueductal gray (l/vlPAG) induces diverse fear responses, depending on the subregions, projection targets, and stimulation intensity. Some l/vlPAG neurons project to the magnocellular nucleus of the medulla (Mc). However, it remains unclear which of the diverse behaviors arising from different intensities of l/vlPAG stimulation are mediated via the l/vlPAG-Mc pathway. Additionally, the role of the l/vlPAG-Mc pathway activation in driving negative or positive valence-related behavior is unknown. To address these questions, we used optogenetics to stimulate Mc-projecting l/vlPAG neurons at two levels of light intensity and analyzed the resulting behavioral changes. Strong stimulation of Mc-projecting l/vlPAG neurons induced flight behavior, whereas weak stimulation elicited a freezing response. Real-time and conditioned place aversion tests indicated that strong stimulation was aversive. These findings suggest that strong stimulation of Mc-projecting l/vlPAG neurons induces active defensive behavior and behavioral aversion, while weak stimulation induces passive defensive behavior.http://www.sciencedirect.com/science/article/pii/S0168010225001221Periaqueductal grayMagnocellular nucleus of the medullaOptogeneticsFiber photometryFear responseFreezing |
| spellingShingle | Yuki Honshuku Yuki Yamaguchi Koki Kawazoe Yuki Nishida Yuki Kurauchi Masabumi Minami Hiroshi Katsuki Natsuko Hitora-Imamura Functional analysis of periaqueductal gray neurons projecting to the medulla in active and passive defensive behaviors Neuroscience Research Periaqueductal gray Magnocellular nucleus of the medulla Optogenetics Fiber photometry Fear response Freezing |
| title | Functional analysis of periaqueductal gray neurons projecting to the medulla in active and passive defensive behaviors |
| title_full | Functional analysis of periaqueductal gray neurons projecting to the medulla in active and passive defensive behaviors |
| title_fullStr | Functional analysis of periaqueductal gray neurons projecting to the medulla in active and passive defensive behaviors |
| title_full_unstemmed | Functional analysis of periaqueductal gray neurons projecting to the medulla in active and passive defensive behaviors |
| title_short | Functional analysis of periaqueductal gray neurons projecting to the medulla in active and passive defensive behaviors |
| title_sort | functional analysis of periaqueductal gray neurons projecting to the medulla in active and passive defensive behaviors |
| topic | Periaqueductal gray Magnocellular nucleus of the medulla Optogenetics Fiber photometry Fear response Freezing |
| url | http://www.sciencedirect.com/science/article/pii/S0168010225001221 |
| work_keys_str_mv | AT yukihonshuku functionalanalysisofperiaqueductalgrayneuronsprojectingtothemedullainactiveandpassivedefensivebehaviors AT yukiyamaguchi functionalanalysisofperiaqueductalgrayneuronsprojectingtothemedullainactiveandpassivedefensivebehaviors AT kokikawazoe functionalanalysisofperiaqueductalgrayneuronsprojectingtothemedullainactiveandpassivedefensivebehaviors AT yukinishida functionalanalysisofperiaqueductalgrayneuronsprojectingtothemedullainactiveandpassivedefensivebehaviors AT yukikurauchi functionalanalysisofperiaqueductalgrayneuronsprojectingtothemedullainactiveandpassivedefensivebehaviors AT masabumiminami functionalanalysisofperiaqueductalgrayneuronsprojectingtothemedullainactiveandpassivedefensivebehaviors AT hiroshikatsuki functionalanalysisofperiaqueductalgrayneuronsprojectingtothemedullainactiveandpassivedefensivebehaviors AT natsukohitoraimamura functionalanalysisofperiaqueductalgrayneuronsprojectingtothemedullainactiveandpassivedefensivebehaviors |