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

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.
项目概要 拟议的工作解决了 NEI 大胆目标倡议强调的一个问题,即“对于 解决”:确定再生受损神经元并促进其与正确目标重新连接的方法 在中枢神经系统中。在小鼠中,被压碎的视神经可以通过同时操作而再生 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 连接因为它们长成萎缩的丘脑,其对皮质的输入减弱。因此, 功能再生需要加强代表受损眼睛的丘脑皮质输入以重新 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 发育时,来自同侧眼睛的微弱传入输入必须与皮层中制定的映射相匹配 已经被对侧眼所支配。该提案研究了初级视觉中的电路机制 初级视觉皮层的成功再生和弱输入整合所必需的皮层,使用in- 体内双光子显微镜观察警觉小鼠的钙活性和全细胞切片电生理学,然后进行测试 在成年期诱发类似情况的有效性。总体假设是,划分 树突活动促进新输入大规模整合到初级视觉皮层。初步数据 表明直接胆碱能输入一类抑制性神经元,即定期尖峰的生长抑素- 表达抑制树突的中间神经元随着关键期的结束而丢失,导致这些神经元发生转变 从划分的树突活动到更同步的活动。生长抑素的化学遗传学控制 中间神经元将用于促进成人皮质中的树突区室化,并测试这是否 增强再生。这些实验有望揭示新的机制,解释如何 视觉发育关键时期的结束会降低建立和加强视觉发育的能力 皮质中的突触连接。从长远来看,这些知识可能会促进弱投入的纳入 在成年期受伤或患病后的再生过程中,将其集中到适当的目标上,这将实现 NEI 的主要目标是改善视力丧失的治疗选择。

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。
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
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Joshua Trachtenberg其他文献

Joshua Trachtenberg的其他文献

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{{ 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 Core
成像核心
  • 批准号:
    8110618
  • 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:
    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:
Imaging Core
成像核心
  • 批准号:
    7625008
  • 财政年份:
    2008
  • 资助金额:
    $ 39.75万
  • 项目类别:

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