Loss of oxytocin receptors in hilar mossy cells impairs social discrimination
Hippocampal oxytocin receptor (OXTR) signaling is crucial for discrimination of social stimuli to guide social recognition, but circuit mechanisms and cell types involved remain incompletely understood. Here, we report a role for OXTR-expressing hilar mossy cells (MCs) of the dentate gyrus in social...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123003273 |
| _version_ | 1797653723479015424 |
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| author | Yu-Chieh Hung Yi-Jen Wu Miao-Er Chien Yu-Ting Lin Cheng-Fang Tsai Kuei-Sen Hsu |
| author_facet | Yu-Chieh Hung Yi-Jen Wu Miao-Er Chien Yu-Ting Lin Cheng-Fang Tsai Kuei-Sen Hsu |
| author_sort | Yu-Chieh Hung |
| collection | DOAJ |
| description | Hippocampal oxytocin receptor (OXTR) signaling is crucial for discrimination of social stimuli to guide social recognition, but circuit mechanisms and cell types involved remain incompletely understood. Here, we report a role for OXTR-expressing hilar mossy cells (MCs) of the dentate gyrus in social stimulus discrimination by regulating granule cell (GC) activity. Using a Cre-loxP recombination approach, we found that ablation of Oxtr from MCs impairs discrimination of social, but not object, stimuli in adult male mice. Ablation of MC Oxtr increases spontaneous firing rate of GCs, synaptic excitation to inhibition ratio of MC-to-GC circuit, and GC firing when temporally associated with the lateral perforant path inputs. Using mouse hippocampal slices, we found that bath application of OXTR agonist [Thr4,Gly7]-oxytocin causes membrane depolarization and increases MC firing activity. Optogenetic activation of MC-to-GC circuit ameliorates social discrimination deficit in MC OXTR deficient mice. Together, our results uncover a previously unknown role of MC OXTR signaling for discrimination of social stimuli and delineate a MC-to-GC circuit responsible for social information processing. |
| first_indexed | 2024-03-11T16:48:45Z |
| format | Article |
| id | doaj.art-f346f313adc94710985b0f5878f9c145 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-03-11T16:48:45Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-f346f313adc94710985b0f5878f9c1452023-10-22T04:48:11ZengElsevierNeurobiology of Disease1095-953X2023-10-01187106311Loss of oxytocin receptors in hilar mossy cells impairs social discriminationYu-Chieh Hung0Yi-Jen Wu1Miao-Er Chien2Yu-Ting Lin3Cheng-Fang Tsai4Kuei-Sen Hsu5Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70457, Taiwan; Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, TaiwanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70457, TaiwanInstitute of Systems Neuroscience, College of Life Science, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Physical Medicine and Rehabilitation, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60002, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Corresponding author at: Department of Physical Medicine and Rehabilitation, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60002, Taiwan.Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Corresponding author at: Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Rd., Tainan 70101, Taiwan.Hippocampal oxytocin receptor (OXTR) signaling is crucial for discrimination of social stimuli to guide social recognition, but circuit mechanisms and cell types involved remain incompletely understood. Here, we report a role for OXTR-expressing hilar mossy cells (MCs) of the dentate gyrus in social stimulus discrimination by regulating granule cell (GC) activity. Using a Cre-loxP recombination approach, we found that ablation of Oxtr from MCs impairs discrimination of social, but not object, stimuli in adult male mice. Ablation of MC Oxtr increases spontaneous firing rate of GCs, synaptic excitation to inhibition ratio of MC-to-GC circuit, and GC firing when temporally associated with the lateral perforant path inputs. Using mouse hippocampal slices, we found that bath application of OXTR agonist [Thr4,Gly7]-oxytocin causes membrane depolarization and increases MC firing activity. Optogenetic activation of MC-to-GC circuit ameliorates social discrimination deficit in MC OXTR deficient mice. Together, our results uncover a previously unknown role of MC OXTR signaling for discrimination of social stimuli and delineate a MC-to-GC circuit responsible for social information processing.http://www.sciencedirect.com/science/article/pii/S0969996123003273Oxytocin receptorMossy cellGranule cellSocial discriminationNovel object recognitionHippocampus |
| spellingShingle | Yu-Chieh Hung Yi-Jen Wu Miao-Er Chien Yu-Ting Lin Cheng-Fang Tsai Kuei-Sen Hsu Loss of oxytocin receptors in hilar mossy cells impairs social discrimination Neurobiology of Disease Oxytocin receptor Mossy cell Granule cell Social discrimination Novel object recognition Hippocampus |
| title | Loss of oxytocin receptors in hilar mossy cells impairs social discrimination |
| title_full | Loss of oxytocin receptors in hilar mossy cells impairs social discrimination |
| title_fullStr | Loss of oxytocin receptors in hilar mossy cells impairs social discrimination |
| title_full_unstemmed | Loss of oxytocin receptors in hilar mossy cells impairs social discrimination |
| title_short | Loss of oxytocin receptors in hilar mossy cells impairs social discrimination |
| title_sort | loss of oxytocin receptors in hilar mossy cells impairs social discrimination |
| topic | Oxytocin receptor Mossy cell Granule cell Social discrimination Novel object recognition Hippocampus |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123003273 |
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