Inhibitory Regulation of Neural Circuit Plasticity in Visual Cortex
视觉皮层神经回路可塑性的抑制调节
基本信息
- 批准号:10468236
- 负责人:
- 金额:$ 39.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylcholineAddressAdolescentAdultAffectAmblyopiaAnimal ModelApicalArousalAtrophicBlindnessBrainCalciumCataractCellsCharacteristicsContralateralD CellsDataDendritesDiseaseElectrophysiology (science)EyeFunctional RegenerationGlaucomaGoalsGrowthInjuryInterneuronsIpsilateralKnowledgeLearningMapsMeasuresMediatingMusNatural regenerationNerve DegenerationNeuraxisNeuronsOcular DominanceOptic NerveParvalbuminsPathway interactionsPropertyPyramidal CellsRecoveryResearch PersonnelRoleSliceSomatostatinSynapsesSynaptic plasticityTestingThalamic structureTherapeuticVasoactive Intestinal PeptideVision DisordersVisualVisual CortexWorkarea striatabasal forebrainbasecholinergiccommon treatmentcritical periodeffectiveness evaluationeffectiveness testingexperimental studyhippocampal pyramidal neuronimprovedin vivoinhibitory neuronmonocular deprivationnerve injuryneural circuitneuronal cell bodyneuroregulationnovelnovel strategiespostnatal developmentreceptive fieldrelating to nervous systemresponsetherapy outcometwo photon microscopyvision development
项目摘要
Project Summary
The proposed work addresses a problem highlighted by the NEI Audacious Goals Initiative as “essential to
resolve”: identifying ways to regenerate damaged neurons and promote their reconnection to the correct targets
in the central nervous system. In mice, a crushed optic nerve can be regenerated by concurrent manipulation of
growth-control pathways and neural activity. Yet these regenerating optic nerves may not form appropriate
connections because they grow into an atrophied thalamus whose inputs to cortex are weakened. Thus,
functional regeneration requires strengthening of thalamocortical inputs representing the damaged eye to re-
establish binocular mapping of visual space onto cortical circuits. Similar challenges are faced in early postnatal
development, when a weak incoming input from the ipsilateral eye must match the mapping laid down in a cortex
already dominated by the contralateral eye. This proposal examines the circuit mechanisms in primary visual
cortex necessary for successful regeneration and integration of weak inputs in primary visual cortex, using in-
vivo two-photon microscopy of calcium activity in alert mice and whole-cell slice electrophysiology, and then tests
the effectiveness of inducing similar conditions in adulthood. The overall hypothesis is that compartmentalized
dendritic activity promotes large-scale integration of new inputs into primary visual cortex. Preliminary data
suggest that direct cholinergic input to one class of inhibitory neurons, the regular-spiking, somatostatin-
expressing interneurons that inhibit dendrites, is lost as the critical period closes, leading these neurons to shift
from compartmentalized dendritic activity to more synchronous activity. Chemogenetic control of somatostatin
interneurons will be used to promote dendritic compartmentalization in adult cortex and to test whether this
enhances regeneration. These experiments are expected to reveal new mechanisms that explain how the
closure of a critical period in visual development reduces the capacity for establishment and strengthening of
synaptic connections in cortex. In the long term, this knowledge is likely to promote incorporation of weak inputs
onto their appropriate targets during regeneration after injury or disease in adulthood, which would achieve a
key goal of the NEI and improve treatment options for vision loss.
项目摘要
拟议的工作解决了NEI大胆目标倡议强调的一个问题,该问题“对于
解决”:确定再生受损神经元并促进其重新连接到正确目标的方法
在中枢神经系统中。在小鼠中,可以通过同时操作
生长控制途径和神经活动。然而,这些再生的视神经可能无法形成适当的
因为它们生长成萎缩的丘脑,丘脑对皮层的输入减弱。因此,在本发明中,
功能性再生需要加强代表受损眼睛的丘脑皮质输入,
建立视觉空间到皮层回路的双眼映射。产后早期也面临类似的挑战。
当来自同侧眼睛的微弱输入必须与皮层中的映射相匹配时,
已经被对侧眼控制了本研究旨在探讨初级视觉系统的电路机制,
皮质必要的成功再生和整合弱输入在初级视觉皮层,使用在-
活体双光子显微镜检查alert小鼠的钙活性和全细胞切片电生理,然后进行测试
在成年期诱导类似条件的有效性。总的假设是,
树突活动促进新输入到初级视觉皮层的大规模整合。初步数据
表明胆碱能直接输入到一类抑制性神经元,即有规律尖峰,生长抑素-
表达抑制树突的中间神经元,随着关键期的结束而丢失,导致这些神经元转移
从区室化的树突活动到更同步的活动。生长抑素的化学发生调控
interneurons将用于促进成年皮层中的树突区室化,并测试这是否
增强再生能力。预计这些实验将揭示新的机制,解释如何
视觉发展的关键时期的结束降低了建立和加强
皮层的突触连接从长远来看,这种知识可能会促进弱投入的整合
在成年期受伤或疾病后的再生过程中,将其适当的目标,这将实现
NEI的关键目标,并改善视力丧失的治疗方案。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Development of Receptive Field Tuning Properties in Mouse Binocular Primary Visual Cortex.
小鼠双眼初级视觉皮层感受野调节特性的发展。
- DOI:10.1523/jneurosci.1702-21.2022
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Tan,Liming;Ringach,DarioL;Trachtenberg,JoshuaT
- 通讯作者:Trachtenberg,JoshuaT
Parvalbumin Interneurons: All Forest, No Trees.
- DOI:10.1016/j.neuron.2015.06.041
- 发表时间:2015-07-15
- 期刊:
- 影响因子:16.2
- 作者:Trachtenberg JT
- 通讯作者:Trachtenberg JT
Competition, inhibition, and critical periods of cortical plasticity.
- DOI:10.1016/j.conb.2015.06.006
- 发表时间:2015-12
- 期刊:
- 影响因子:5.7
- 作者:Trachtenberg JT
- 通讯作者:Trachtenberg JT
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Joshua Trachtenberg其他文献
Joshua Trachtenberg的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Joshua Trachtenberg', 18)}}的其他基金
Inhibitory regulation of neural circuit plasticity in visual cortex
视觉皮层神经回路可塑性的抑制调节
- 批准号:
8725168 - 财政年份:2013
- 资助金额:
$ 39.75万 - 项目类别:
Inhibitory Regulation of Neural Circuit Plasticity in Visual Cortex
视觉皮层神经回路可塑性的抑制调节
- 批准号:
10245254 - 财政年份:2013
- 资助金额:
$ 39.75万 - 项目类别:
Inhibitory Regulation of Neural Circuit Plasticity in Visual Cortex
视觉皮层神经回路可塑性的抑制调节
- 批准号:
10004651 - 财政年份:2013
- 资助金额:
$ 39.75万 - 项目类别:
Inhibitory regulation of neural circuit plasticity in visual cortex
视觉皮层神经回路可塑性的抑制调节
- 批准号:
8594027 - 财政年份:2013
- 资助金额:
$ 39.75万 - 项目类别:
Inhibitory regulation of neural circuit plasticity in visual cortex
视觉皮层神经回路可塑性的抑制调节
- 批准号:
8927645 - 财政年份:2013
- 资助金额:
$ 39.75万 - 项目类别:
Imaging PTEN-induced changes in adult cortical structure and function in vivo
对 PTEN 诱导的成人皮质结构和功能的体内变化进行成像
- 批准号:
8211003 - 财政年份:2010
- 资助金额:
$ 39.75万 - 项目类别:
Imaging PTEN-induced changes in adult cortical structure and function in vivo
对 PTEN 诱导的成人皮质结构和功能的体内变化进行成像
- 批准号:
7886118 - 财政年份:2010
- 资助金额:
$ 39.75万 - 项目类别:
Imaging PTEN-induced changes in adult cortical structure and function in vivo
对 PTEN 诱导的成人皮质结构和功能的体内变化进行成像
- 批准号:
8054250 - 财政年份:2010
- 资助金额:
$ 39.75万 - 项目类别:
相似海外基金
Enhancing Structural Competency in School-Based Health Centers to Address LGBTQ+ Adolescent Health Equity
增强校本健康中心的结构能力,以解决 LGBTQ 青少年健康公平问题
- 批准号:
10608426 - 财政年份:2023
- 资助金额:
$ 39.75万 - 项目类别:
Application and feasability of a brief digital screening tool to address parental and adolescent tobacco and electronic cigarette use in pediatric medical care - a pilot study
简短的数字筛查工具的应用和可行性,以解决儿科医疗中父母和青少年烟草和电子烟的使用问题 - 一项试点研究
- 批准号:
486580 - 财政年份:2022
- 资助金额:
$ 39.75万 - 项目类别:
Studentship Programs
Co-design of an intervention to address alcohol use among adolescent boys and young men in Tanzania
共同设计一项干预措施,解决坦桑尼亚青春期男孩和年轻男性的饮酒问题
- 批准号:
MR/V032380/1 - 财政年份:2022
- 资助金额:
$ 39.75万 - 项目类别:
Research Grant
Complex intervention to optimise adolescent BMI pre-conception to address the double burden of malnutrition: A RCT in rural and urban South Africa
优化青少年孕前体重指数以解决营养不良的双重负担的复杂干预措施:南非农村和城市的随机对照试验
- 批准号:
MR/V005790/1 - 财政年份:2021
- 资助金额:
$ 39.75万 - 项目类别:
Research Grant
Application of a brief digital screening tool to address parental and adolescent tobacco and electronic cigarette use in pediatric medical care
应用简短的数字筛查工具来解决儿科医疗中父母和青少年烟草和电子烟的使用问题
- 批准号:
455984 - 财政年份:2021
- 资助金额:
$ 39.75万 - 项目类别:
Operating Grants
Complex intervention to optimise adolescent BMI pre-conception to address the double burden of malnutrition: A RCT in rural and urban South Africa
优化青少年孕前体重指数以解决营养不良的双重负担的复杂干预措施:南非农村和城市的随机对照试验
- 批准号:
MR/V005790/2 - 财政年份:2021
- 资助金额:
$ 39.75万 - 项目类别:
Research Grant
Development of the Cannabis Actions and Practices (CAP): A Parent-Focused Intervention to Address Adolescent Marijuana Use
大麻行动和实践 (CAP) 的发展:以家长为中心的干预措施,解决青少年大麻使用问题
- 批准号:
10057761 - 财政年份:2020
- 资助金额:
$ 39.75万 - 项目类别:
Development of the Cannabis Actions and Practices (CAP): A Parent-Focused Intervention to Address Adolescent Marijuana Use
大麻行动和实践 (CAP) 的发展:以家长为中心的干预措施,解决青少年大麻使用问题
- 批准号:
10213683 - 财政年份:2020
- 资助金额:
$ 39.75万 - 项目类别:
Targeted interventions to address the multi-level effects of gender-based violence on PrEP uptake and adherence among adolescent girls and young women in Kenya
有针对性的干预措施,以解决性别暴力对肯尼亚少女和年轻妇女接受和坚持 PrEP 的多层面影响
- 批准号:
9403567 - 财政年份:2017
- 资助金额:
$ 39.75万 - 项目类别:
Designing targeted interventions to address HIV vulnerabilities and improve clinical outcomes among conflict affected adolescent girls and young women under 25 in Northern Uganda
设计有针对性的干预措施,以解决乌干达北部受冲突影响的少女和 25 岁以下年轻妇女的艾滋病毒脆弱性并改善临床结果
- 批准号:
356145 - 财政年份:2016
- 资助金额:
$ 39.75万 - 项目类别:
Operating Grants