Neuroligin 1 Regulates Autistic‐Like Repetitive Behavior through Modulating the Activity of Striatal D2 Receptor‐Expressing Medium Spiny Neurons
Abstract Restricted and repetitive behavior (RRB) is a primary symptom of autism spectrum disorder (ASD), which poses a significant risk to individuals' health and is becoming increasingly prevalent. However, the specific cellular and neural circuit mechanisms underlying the generation of RRB r...
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202410728 |
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| author | Dandan Lv An Liu Ziyue Yi Mingdao Mu Miao Wu Xingcan Li Kun Cao Ruining Liu Zhengping Jia Junhai Han Wei Xie |
| author_facet | Dandan Lv An Liu Ziyue Yi Mingdao Mu Miao Wu Xingcan Li Kun Cao Ruining Liu Zhengping Jia Junhai Han Wei Xie |
| author_sort | Dandan Lv |
| collection | DOAJ |
| description | Abstract Restricted and repetitive behavior (RRB) is a primary symptom of autism spectrum disorder (ASD), which poses a significant risk to individuals' health and is becoming increasingly prevalent. However, the specific cellular and neural circuit mechanisms underlying the generation of RRB remain unclear. In this study, it is reported that the absence of the ASD‐related protein Neuroligin 1 (NLGN1) in dopamine receptor D2‐expressing medium spiny neurons (D2‐MSNs) in the dorsal striatum is associated with the duration and frequency of self‐grooming and digging behaviors. The Nlgn1‐deficient D2‐MSNs are hyperactivated, which correlates with excessive self‐grooming and digging behaviors. Inhibiting the activity of D2‐MSNs reduces the duration and frequency of these RRBs. Furthermore, it is demonstrated that the generation of self‐grooming and digging behaviors depends on distinct patterns of D2‐MSN activity. Finally, through single‐nucleus RNA sequencing (sn‐RNAseq) and protein detection verification, it is revealed that the overactivation of protein kinase C (PKC) in Nlgn1‐deficient mice contributes to excessive repetitive behaviors and increased neuronal excitability. In this study, potential mechanisms are proposed for the generation of self‐grooming and digging behaviors, as well as suggest possible treatments and interventions ASD. |
| format | Article |
| id | doaj-art-605267d471a048ff8a7cee4b499ed13c |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-605267d471a048ff8a7cee4b499ed13c2025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202410728Neuroligin 1 Regulates Autistic‐Like Repetitive Behavior through Modulating the Activity of Striatal D2 Receptor‐Expressing Medium Spiny NeuronsDandan Lv0An Liu1Ziyue Yi2Mingdao Mu3Miao Wu4Xingcan Li5Kun Cao6Ruining Liu7Zhengping Jia8Junhai Han9Wei Xie10The Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaThe Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaThe Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaThe Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaThe Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaThe Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaThe Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaThe Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaNeurosciences & Mental Health The Hospital for Sick Children 555 University Ave. Toronto Ontario M5G 1×8 CanadaThe Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaThe Key Laboratory of Developmental Genes and Human Disease The School of Life Science and Technology Southeast University 2 Sipailou Road Nanjing 210096 ChinaAbstract Restricted and repetitive behavior (RRB) is a primary symptom of autism spectrum disorder (ASD), which poses a significant risk to individuals' health and is becoming increasingly prevalent. However, the specific cellular and neural circuit mechanisms underlying the generation of RRB remain unclear. In this study, it is reported that the absence of the ASD‐related protein Neuroligin 1 (NLGN1) in dopamine receptor D2‐expressing medium spiny neurons (D2‐MSNs) in the dorsal striatum is associated with the duration and frequency of self‐grooming and digging behaviors. The Nlgn1‐deficient D2‐MSNs are hyperactivated, which correlates with excessive self‐grooming and digging behaviors. Inhibiting the activity of D2‐MSNs reduces the duration and frequency of these RRBs. Furthermore, it is demonstrated that the generation of self‐grooming and digging behaviors depends on distinct patterns of D2‐MSN activity. Finally, through single‐nucleus RNA sequencing (sn‐RNAseq) and protein detection verification, it is revealed that the overactivation of protein kinase C (PKC) in Nlgn1‐deficient mice contributes to excessive repetitive behaviors and increased neuronal excitability. In this study, potential mechanisms are proposed for the generation of self‐grooming and digging behaviors, as well as suggest possible treatments and interventions ASD.https://doi.org/10.1002/advs.202410728Autism Spectrum Disorder (ASD)D2‐MSNneuroligin1restricted and repetitive behavior (RRB)striatum |
| spellingShingle | Dandan Lv An Liu Ziyue Yi Mingdao Mu Miao Wu Xingcan Li Kun Cao Ruining Liu Zhengping Jia Junhai Han Wei Xie Neuroligin 1 Regulates Autistic‐Like Repetitive Behavior through Modulating the Activity of Striatal D2 Receptor‐Expressing Medium Spiny Neurons Advanced Science Autism Spectrum Disorder (ASD) D2‐MSN neuroligin1 restricted and repetitive behavior (RRB) striatum |
| title | Neuroligin 1 Regulates Autistic‐Like Repetitive Behavior through Modulating the Activity of Striatal D2 Receptor‐Expressing Medium Spiny Neurons |
| title_full | Neuroligin 1 Regulates Autistic‐Like Repetitive Behavior through Modulating the Activity of Striatal D2 Receptor‐Expressing Medium Spiny Neurons |
| title_fullStr | Neuroligin 1 Regulates Autistic‐Like Repetitive Behavior through Modulating the Activity of Striatal D2 Receptor‐Expressing Medium Spiny Neurons |
| title_full_unstemmed | Neuroligin 1 Regulates Autistic‐Like Repetitive Behavior through Modulating the Activity of Striatal D2 Receptor‐Expressing Medium Spiny Neurons |
| title_short | Neuroligin 1 Regulates Autistic‐Like Repetitive Behavior through Modulating the Activity of Striatal D2 Receptor‐Expressing Medium Spiny Neurons |
| title_sort | neuroligin 1 regulates autistic like repetitive behavior through modulating the activity of striatal d2 receptor expressing medium spiny neurons |
| topic | Autism Spectrum Disorder (ASD) D2‐MSN neuroligin1 restricted and repetitive behavior (RRB) striatum |
| url | https://doi.org/10.1002/advs.202410728 |
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