Pub Date : 2024-07-01DOI: 10.1038/s41583-024-00841-x
Sian Lewis
The maladaptive reward learning associated with morphine administration is shown here to be mediated by changes in dopamine-release dynamics in reward circuitry resulting from increased myelination specifically in the ventral tegmental area.
{"title":"Wrapping up reward","authors":"Sian Lewis","doi":"10.1038/s41583-024-00841-x","DOIUrl":"10.1038/s41583-024-00841-x","url":null,"abstract":"The maladaptive reward learning associated with morphine administration is shown here to be mediated by changes in dopamine-release dynamics in reward circuitry resulting from increased myelination specifically in the ventral tegmental area.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":28.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1038/s41583-024-00843-9
Katherine Whalley
A study maps the effects of ageing and sex on gene regulation in specific human cortical cell types.
一项研究描绘了衰老和性别对特定人类皮质细胞类型基因调控的影响。
{"title":"Mapping the cell-type-specific effects of ageing in the human cortex","authors":"Katherine Whalley","doi":"10.1038/s41583-024-00843-9","DOIUrl":"10.1038/s41583-024-00843-9","url":null,"abstract":"A study maps the effects of ageing and sex on gene regulation in specific human cortical cell types.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":28.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-27DOI: 10.1038/s41583-024-00836-8
Jacob A. Miller, Christos Constantinidis
The lateral prefrontal cortex (PFC) in humans and other primates is critical for immediate, goal-directed behaviour and working memory, which are classically considered distinct from the cognitive and neural circuits that support long-term learning and memory. Over the past few years, a reconsideration of this textbook perspective has emerged, in that different timescales of memory-guided behaviour are in constant interaction during the pursuit of immediate goals. Here, we will first detail how neural activity related to the shortest timescales of goal-directed behaviour (which requires maintenance of current states and goals in working memory) is sculpted by long-term knowledge and learning — that is, how the past informs present behaviour. Then, we will outline how learning across different timescales (from seconds to years) drives plasticity in the primate lateral PFC, from single neuron firing rates to mesoscale neuroimaging activity patterns. Finally, we will review how, over days and months of learning, dense local and long-range connectivity patterns in PFC facilitate longer-lasting changes in population activity by changing synaptic weights and recruiting additional neural resources to inform future behaviour. Our Review sheds light on how the machinery of plasticity in PFC circuits facilitates the integration of learned experiences across time to best guide adaptive behaviour. The prefrontal cortex is critical for working memory, over a timescale of seconds. In this Review, Miller and Constantinidis examine how the prefrontal cortex facilitates the integration of memory systems across other timescales as well. In this framework of prefrontal learning, short-term memory and long-term memory interact to serve goal-directed behaviour.
{"title":"Timescales of learning in prefrontal cortex","authors":"Jacob A. Miller, Christos Constantinidis","doi":"10.1038/s41583-024-00836-8","DOIUrl":"10.1038/s41583-024-00836-8","url":null,"abstract":"The lateral prefrontal cortex (PFC) in humans and other primates is critical for immediate, goal-directed behaviour and working memory, which are classically considered distinct from the cognitive and neural circuits that support long-term learning and memory. Over the past few years, a reconsideration of this textbook perspective has emerged, in that different timescales of memory-guided behaviour are in constant interaction during the pursuit of immediate goals. Here, we will first detail how neural activity related to the shortest timescales of goal-directed behaviour (which requires maintenance of current states and goals in working memory) is sculpted by long-term knowledge and learning — that is, how the past informs present behaviour. Then, we will outline how learning across different timescales (from seconds to years) drives plasticity in the primate lateral PFC, from single neuron firing rates to mesoscale neuroimaging activity patterns. Finally, we will review how, over days and months of learning, dense local and long-range connectivity patterns in PFC facilitate longer-lasting changes in population activity by changing synaptic weights and recruiting additional neural resources to inform future behaviour. Our Review sheds light on how the machinery of plasticity in PFC circuits facilitates the integration of learned experiences across time to best guide adaptive behaviour. The prefrontal cortex is critical for working memory, over a timescale of seconds. In this Review, Miller and Constantinidis examine how the prefrontal cortex facilitates the integration of memory systems across other timescales as well. In this framework of prefrontal learning, short-term memory and long-term memory interact to serve goal-directed behaviour.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":28.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-27DOI: 10.1038/s41583-024-00830-0
David Williams
Bradykinesia, or slowness of movement, is a defining feature of Parkinson disease (PD) and a major contributor to the negative effects on quality of life associated with this disorder and related conditions. A dominant pathophysiological model of bradykinesia in PD has existed for approximately 30 years and has been the basis for the development of several therapeutic interventions, but accumulating evidence has made this model increasingly untenable. Although more recent models have been proposed, they also appear to be flawed. In this Perspective, I consider the leading prior models of bradykinesia in PD and argue that a more functionally related model is required, one that considers changes that disrupt the fundamental process of accurate information transmission. In doing so, I review emerging evidence of network level functional connectivity changes, information transfer dysfunction and potential motor code transmission error and present a novel model of bradykinesia in PD that incorporates this evidence. I hope that this model may reconcile inconsistencies in its predecessors and encourage further development of therapeutic interventions. There are a number of models that have attempted to explain why people with Parkinson disease move slowly. In this Perspective, Williams identifies the inconsistencies in these models and suggests that these may be addressed by a different model that considers disordered information transmission as fundamental to slow movement development.
{"title":"Why so slow? Models of parkinsonian bradykinesia","authors":"David Williams","doi":"10.1038/s41583-024-00830-0","DOIUrl":"10.1038/s41583-024-00830-0","url":null,"abstract":"Bradykinesia, or slowness of movement, is a defining feature of Parkinson disease (PD) and a major contributor to the negative effects on quality of life associated with this disorder and related conditions. A dominant pathophysiological model of bradykinesia in PD has existed for approximately 30 years and has been the basis for the development of several therapeutic interventions, but accumulating evidence has made this model increasingly untenable. Although more recent models have been proposed, they also appear to be flawed. In this Perspective, I consider the leading prior models of bradykinesia in PD and argue that a more functionally related model is required, one that considers changes that disrupt the fundamental process of accurate information transmission. In doing so, I review emerging evidence of network level functional connectivity changes, information transfer dysfunction and potential motor code transmission error and present a novel model of bradykinesia in PD that incorporates this evidence. I hope that this model may reconcile inconsistencies in its predecessors and encourage further development of therapeutic interventions. There are a number of models that have attempted to explain why people with Parkinson disease move slowly. In this Perspective, Williams identifies the inconsistencies in these models and suggests that these may be addressed by a different model that considers disordered information transmission as fundamental to slow movement development.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":28.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-20DOI: 10.1038/s41583-024-00839-5
Lauren N. Ross, Dani S. Bassett
{"title":"Reply to ‘Causal prominence for neuroscience’","authors":"Lauren N. Ross, Dani S. Bassett","doi":"10.1038/s41583-024-00839-5","DOIUrl":"10.1038/s41583-024-00839-5","url":null,"abstract":"","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":28.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41583-024-00839-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The power of direct observation: discovery of REM sleep","authors":"Danqian Liu","doi":"10.1038/s41583-024-00840-y","DOIUrl":"10.1038/s41583-024-00840-y","url":null,"abstract":"In this Journal Club, Danqian Liu describes the 1953 paper that reported the discovery of rapid eye movement (REM) sleep.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":28.7,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1038/s41583-024-00829-7
Jingjing Gao, Swetharajan Gunasekar, Ziting (Judy) Xia, Kiruba Shalin, Christopher Jiang, Hao Chen, Dongtak Lee, Sohyung Lee, Nishkal D. Pisal, James N. Luo, Ana Griciuc, Jeffrey M. Karp, Rudolph Tanzi, Nitin Joshi
Gene therapy is emerging as a powerful tool to modulate abnormal gene expression, a hallmark of most CNS disorders. The transformative potentials of recently approved gene therapies for the treatment of spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and active cerebral adrenoleukodystrophy are encouraging further development of this approach. However, most attempts to translate gene therapy to the clinic have failed to make it to market. There is an urgent need not only to tailor the genes that are targeted to the pathology of interest but to also address delivery challenges and thereby maximize the utility of genetic tools. In this Review, we provide an overview of gene therapy modalities for CNS diseases, emphasizing the interconnectedness of different delivery strategies and routes of administration. Important gaps in understanding that could accelerate the clinical translatability of CNS genetic interventions are addressed, and we present lessons learned from failed clinical trials that may guide the future development of gene therapies for the treatment and management of CNS disorders. Recent advances in the development of gene therapy tools provide hope that these approaches might modulate the altered gene expression that characterizes many CNS disorders. Gao et al. provide an overview of current gene therapy strategies, highlighting the interdependence of therapeutic modality, delivery vehicle and administration route for translational success.
{"title":"Gene therapy for CNS disorders: modalities, delivery and translational challenges","authors":"Jingjing Gao, Swetharajan Gunasekar, Ziting (Judy) Xia, Kiruba Shalin, Christopher Jiang, Hao Chen, Dongtak Lee, Sohyung Lee, Nishkal D. Pisal, James N. Luo, Ana Griciuc, Jeffrey M. Karp, Rudolph Tanzi, Nitin Joshi","doi":"10.1038/s41583-024-00829-7","DOIUrl":"10.1038/s41583-024-00829-7","url":null,"abstract":"Gene therapy is emerging as a powerful tool to modulate abnormal gene expression, a hallmark of most CNS disorders. The transformative potentials of recently approved gene therapies for the treatment of spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and active cerebral adrenoleukodystrophy are encouraging further development of this approach. However, most attempts to translate gene therapy to the clinic have failed to make it to market. There is an urgent need not only to tailor the genes that are targeted to the pathology of interest but to also address delivery challenges and thereby maximize the utility of genetic tools. In this Review, we provide an overview of gene therapy modalities for CNS diseases, emphasizing the interconnectedness of different delivery strategies and routes of administration. Important gaps in understanding that could accelerate the clinical translatability of CNS genetic interventions are addressed, and we present lessons learned from failed clinical trials that may guide the future development of gene therapies for the treatment and management of CNS disorders. Recent advances in the development of gene therapy tools provide hope that these approaches might modulate the altered gene expression that characterizes many CNS disorders. Gao et al. provide an overview of current gene therapy strategies, highlighting the interdependence of therapeutic modality, delivery vehicle and administration route for translational success.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":28.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-11DOI: 10.1038/s41583-024-00835-9
Sabine Krabbe
Sabine Krabbe describes a 1993 study of classical conditioning in the honeybee that provided early insights into the mechanisms of predictive learning.
{"title":"Lessons on predictive learning from the honeybee","authors":"Sabine Krabbe","doi":"10.1038/s41583-024-00835-9","DOIUrl":"10.1038/s41583-024-00835-9","url":null,"abstract":"Sabine Krabbe describes a 1993 study of classical conditioning in the honeybee that provided early insights into the mechanisms of predictive learning.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":28.7,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-10DOI: 10.1038/s41583-024-00832-y
Alexander J. Shackman, Shannon E. Grogans, Andrew S. Fox
{"title":"Fear, anxiety and the functional architecture of the human central extended amygdala","authors":"Alexander J. Shackman, Shannon E. Grogans, Andrew S. Fox","doi":"10.1038/s41583-024-00832-y","DOIUrl":"10.1038/s41583-024-00832-y","url":null,"abstract":"","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":null,"pages":null},"PeriodicalIF":28.7,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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