{"title":"慢性应激通过增加直接通路神经元的兴奋驱动来促进基底神经节的去抑制","authors":"Diana Rodrigues , Patricia Monteiro","doi":"10.1016/j.ynstr.2023.100571","DOIUrl":null,"url":null,"abstract":"<div><p>Chronic stress (CS) is a well-recognized triggering factor in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS), two neuropsychiatric disorders characterized by the presence of stereotypic motor symptoms. Planning and execution of motor actions are controlled by the dorsal striatum, a brain region that promotes or suppresses motor movement by activating striatal neurons from the direct- or indirect-pathway, respectively. Despite the dorsal striatum being affected in motor disorders and by CS exposure, how CS affects the two opposing pathways is not fully understood. Here, we report that CS in mice selectively potentiates the direct-pathway, while sparing the indirect-pathway. Specifically, we show that CS both increases excitation and reduces inhibition over direct-pathway neurons in the dorsomedial striatum (DMS). Furthermore, inhibitory interneurons located in the DMS also display reduced excitatory drive after chronic stress, thus amplifying striatal disinhibition. Altogether, we propose a model where both increased excitatory drive and decreased inhibitory drive in the striatum causes disinhibition of basal ganglia's motor direct pathway - a mechanism that might explain the emergence of motor stereotypies and tic disorders under stress.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"27 ","pages":"Article 100571"},"PeriodicalIF":4.3000,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540042/pdf/","citationCount":"0","resultStr":"{\"title\":\"Chronic stress promotes basal ganglia disinhibition by increasing the excitatory drive of direct-pathway neurons\",\"authors\":\"Diana Rodrigues , Patricia Monteiro\",\"doi\":\"10.1016/j.ynstr.2023.100571\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Chronic stress (CS) is a well-recognized triggering factor in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS), two neuropsychiatric disorders characterized by the presence of stereotypic motor symptoms. Planning and execution of motor actions are controlled by the dorsal striatum, a brain region that promotes or suppresses motor movement by activating striatal neurons from the direct- or indirect-pathway, respectively. Despite the dorsal striatum being affected in motor disorders and by CS exposure, how CS affects the two opposing pathways is not fully understood. Here, we report that CS in mice selectively potentiates the direct-pathway, while sparing the indirect-pathway. Specifically, we show that CS both increases excitation and reduces inhibition over direct-pathway neurons in the dorsomedial striatum (DMS). Furthermore, inhibitory interneurons located in the DMS also display reduced excitatory drive after chronic stress, thus amplifying striatal disinhibition. Altogether, we propose a model where both increased excitatory drive and decreased inhibitory drive in the striatum causes disinhibition of basal ganglia's motor direct pathway - a mechanism that might explain the emergence of motor stereotypies and tic disorders under stress.</p></div>\",\"PeriodicalId\":19125,\"journal\":{\"name\":\"Neurobiology of Stress\",\"volume\":\"27 \",\"pages\":\"Article 100571\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2023-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540042/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurobiology of Stress\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2352289523000590\",\"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 Stress","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352289523000590","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Chronic stress promotes basal ganglia disinhibition by increasing the excitatory drive of direct-pathway neurons
Chronic stress (CS) is a well-recognized triggering factor in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS), two neuropsychiatric disorders characterized by the presence of stereotypic motor symptoms. Planning and execution of motor actions are controlled by the dorsal striatum, a brain region that promotes or suppresses motor movement by activating striatal neurons from the direct- or indirect-pathway, respectively. Despite the dorsal striatum being affected in motor disorders and by CS exposure, how CS affects the two opposing pathways is not fully understood. Here, we report that CS in mice selectively potentiates the direct-pathway, while sparing the indirect-pathway. Specifically, we show that CS both increases excitation and reduces inhibition over direct-pathway neurons in the dorsomedial striatum (DMS). Furthermore, inhibitory interneurons located in the DMS also display reduced excitatory drive after chronic stress, thus amplifying striatal disinhibition. Altogether, we propose a model where both increased excitatory drive and decreased inhibitory drive in the striatum causes disinhibition of basal ganglia's motor direct pathway - a mechanism that might explain the emergence of motor stereotypies and tic disorders under stress.
期刊介绍:
Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal.
Basic, translational and clinical research on the following topics as they relate to stress will be covered:
Molecular substrates and cell signaling,
Genetics and epigenetics,
Stress circuitry,
Structural and physiological plasticity,
Developmental Aspects,
Laboratory models of stress,
Neuroinflammation and pathology,
Memory and Cognition,
Motivational Processes,
Fear and Anxiety,
Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse),
Neuropsychopharmacology.