Carlos Alberto Ortiz-Cruz , Miroslava Peralta-Ramirez , Mateo Alberto Herrera-Murillo , Regina Andrea Mejia-Ortiz , Marcela Palomero-Rivero , Baolin Guo , Uri Nimrod Ramirez-Jarquin , Violeta Gisselle Lopez-Huerta
{"title":"自闭症小鼠Shank3突变模型中一阶和高阶丘脑网状神经元的亚型特异性改变","authors":"Carlos Alberto Ortiz-Cruz , Miroslava Peralta-Ramirez , Mateo Alberto Herrera-Murillo , Regina Andrea Mejia-Ortiz , Marcela Palomero-Rivero , Baolin Guo , Uri Nimrod Ramirez-Jarquin , Violeta Gisselle Lopez-Huerta","doi":"10.1016/j.nbd.2025.107108","DOIUrl":null,"url":null,"abstract":"<div><div>The thalamic reticular nucleus (TRN) is a critical inhibitory structure in the thalamocortical network, playing key roles in sensory processing, attention, cognitive flexibility, and sleep rhythms; importantly these functions are altered in autism spectrum disorder (ASD). The TRN consists mainly of two neuronal subpopulations: first order (FO) neurons, which modulate sensory relay nuclei, and higher-order (HO) neurons, which control associative thalamic circuits. TRN-FO neurons are located in the core region, show a high expression of repetitive burst firing, and are known to contribute to slow-wave oscillations. In contrast, neurons innervating HO thalamic nuclei are in the anterior and peripheral regions of the TRN and have fewer burst firing. These subpopulations provide specialized inhibition to thalamus, but their alterations in ASD have rarely been explored. We evaluated the reticular inhibitory system in thalamic nuclei (FO and HO) in Shank3 KO mice, a well-established monogenic model of ASD. We analyzed electrophysiological properties of targeted TRN neurons, our results show that TRN neurons projecting to FO and HO nuclei exhibit differential changes in Shank3 KO mice, including decreased burst firing in FO projecting neurons, which is crucial for maintaining sleep architecture. Additionally, we examined spontaneous and miniature inhibitory postsynaptic currents (IPSCs), in ventroposteromedial (VPM-FO) and posteromedial (POm-HO) thalamic nuclei. We show a reduction in frequency of spontaneous IPSCs and mIPSCs in VPM and POm. Together, our results show distinct alterations in the inhibitory control of FO and HO thalamic nuclei in Shank3 KO mice, which could contribute to the deficits in sleep and sensory processing observed in ASD.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"216 ","pages":"Article 107108"},"PeriodicalIF":5.6000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Subtype-specific alterations in first- and higher-order thalamic reticular neurons in the Shank3 mutant mouse model of autism\",\"authors\":\"Carlos Alberto Ortiz-Cruz , Miroslava Peralta-Ramirez , Mateo Alberto Herrera-Murillo , Regina Andrea Mejia-Ortiz , Marcela Palomero-Rivero , Baolin Guo , Uri Nimrod Ramirez-Jarquin , Violeta Gisselle Lopez-Huerta\",\"doi\":\"10.1016/j.nbd.2025.107108\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The thalamic reticular nucleus (TRN) is a critical inhibitory structure in the thalamocortical network, playing key roles in sensory processing, attention, cognitive flexibility, and sleep rhythms; importantly these functions are altered in autism spectrum disorder (ASD). The TRN consists mainly of two neuronal subpopulations: first order (FO) neurons, which modulate sensory relay nuclei, and higher-order (HO) neurons, which control associative thalamic circuits. TRN-FO neurons are located in the core region, show a high expression of repetitive burst firing, and are known to contribute to slow-wave oscillations. In contrast, neurons innervating HO thalamic nuclei are in the anterior and peripheral regions of the TRN and have fewer burst firing. These subpopulations provide specialized inhibition to thalamus, but their alterations in ASD have rarely been explored. We evaluated the reticular inhibitory system in thalamic nuclei (FO and HO) in Shank3 KO mice, a well-established monogenic model of ASD. We analyzed electrophysiological properties of targeted TRN neurons, our results show that TRN neurons projecting to FO and HO nuclei exhibit differential changes in Shank3 KO mice, including decreased burst firing in FO projecting neurons, which is crucial for maintaining sleep architecture. Additionally, we examined spontaneous and miniature inhibitory postsynaptic currents (IPSCs), in ventroposteromedial (VPM-FO) and posteromedial (POm-HO) thalamic nuclei. We show a reduction in frequency of spontaneous IPSCs and mIPSCs in VPM and POm. Together, our results show distinct alterations in the inhibitory control of FO and HO thalamic nuclei in Shank3 KO mice, which could contribute to the deficits in sleep and sensory processing observed in ASD.</div></div>\",\"PeriodicalId\":19097,\"journal\":{\"name\":\"Neurobiology of Disease\",\"volume\":\"216 \",\"pages\":\"Article 107108\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurobiology of Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0969996125003250\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969996125003250","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Subtype-specific alterations in first- and higher-order thalamic reticular neurons in the Shank3 mutant mouse model of autism
The thalamic reticular nucleus (TRN) is a critical inhibitory structure in the thalamocortical network, playing key roles in sensory processing, attention, cognitive flexibility, and sleep rhythms; importantly these functions are altered in autism spectrum disorder (ASD). The TRN consists mainly of two neuronal subpopulations: first order (FO) neurons, which modulate sensory relay nuclei, and higher-order (HO) neurons, which control associative thalamic circuits. TRN-FO neurons are located in the core region, show a high expression of repetitive burst firing, and are known to contribute to slow-wave oscillations. In contrast, neurons innervating HO thalamic nuclei are in the anterior and peripheral regions of the TRN and have fewer burst firing. These subpopulations provide specialized inhibition to thalamus, but their alterations in ASD have rarely been explored. We evaluated the reticular inhibitory system in thalamic nuclei (FO and HO) in Shank3 KO mice, a well-established monogenic model of ASD. We analyzed electrophysiological properties of targeted TRN neurons, our results show that TRN neurons projecting to FO and HO nuclei exhibit differential changes in Shank3 KO mice, including decreased burst firing in FO projecting neurons, which is crucial for maintaining sleep architecture. Additionally, we examined spontaneous and miniature inhibitory postsynaptic currents (IPSCs), in ventroposteromedial (VPM-FO) and posteromedial (POm-HO) thalamic nuclei. We show a reduction in frequency of spontaneous IPSCs and mIPSCs in VPM and POm. Together, our results show distinct alterations in the inhibitory control of FO and HO thalamic nuclei in Shank3 KO mice, which could contribute to the deficits in sleep and sensory processing observed in ASD.
期刊介绍:
Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.