Homeostatic plasticity in mouse visual cortex

小鼠视觉皮层的稳态可塑性

• 批准号: BB/M021408/1
• 负责人: Frank Sengpiel
• 金额: $ 47.19万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM021408%2F1
• 关键词: Homeostatic; plasticity; mouse; visual; cortex

The primary visual cortex (V1) is one of the most extensively studied areas of the mammalian brain, not only because it is crucial for our understanding of human vision but also because it has become a model system for studying cellular processes underlying plasticity, learning and memory. Visual experience during a so-called critical period in early childhood shapes the way neurons in V1 respond to visual stimuli throughout life, and any conditions that put one eye at a disadvantage (such as cross-eyes or a cataract) can cause amblyopia ('lazy eye') if not corrected in time. Up to 4% of the population suffer from this condition. In recent years research (including in our own labs) has increasingly employed mice in an effort to discover the cellular and molecular mechanisms of the underlying processes, using monocular eyelid suture ('monocular deprivation') as the standard paradigm to challenge visual cortex plasticity. Studies have identified the involvement of different mechanisms for different lengths of monocular deprivation and at different ages. One of these is 'homeostatic plasticity', an important ability of neurons to regulate their excitability in order to maintain stable network activity, balancing the effects of long-term synaptic potentiation and depression. This is thought to be mediated by a process called synaptic scaling. We have previously discovered evidence for the operation of this mechanism following monocular deprivation in juvenile but not adult mouse visual cortex. We also showed that the GluA1 subunit of the AMPA receptor which is the main mediator of excitatory transmission in the visual cortex is important for homeostatic plasticity.In addition to monocular deprivation, homeostatic plasticity can be triggered by placing animals in complete darkness, presumably because this depresses overall cortical activity dramatically. Dark exposure has recently been shown to promote recovery from monocular deprivation in adolescent rats and cats and may therefore present an opportunity to treat amblyopia beyond the end of the critical period. The latest work in our lab demonstrates that just a few days of dark exposure restore plasticity in V1 of mice which have been monocular deprived beyond the end of the critical period.Here we address key questions regarding the cellular mechanisms of homeostatic plasticity in juvenile and adult mice, as well as of the effects of dark exposure on plasticity. We shall investigate,1) By which mechanism does dark exposure promote plasticity in the adult visual cortex? Does it enable the GluA1 dependent homeostatic plasticity that operates in the juvenile cortex, or does it simply enhance existing mechanisms of adult plasticity (such as long-term potentiation)? 2) Is the restoration of visual cortex plasticity in adult mice by means of dark exposure behaviourally significant? In other words, do mice perform better on visually guided tasks, using the previously deprived eye, after a period of dark exposure?3) Which of the cells in V1 mediate the GluA1 dependent plasticity? Using molecular biology techniques we shall inhibit the production of GluA1 in each of 3 main classes of cells (excitatory pyramidal neurons, parvalbumin positive inhibitory neurons and astrocytes) in turn to assess whether plasticity in response to monocular deprivation in young mice is affected.4) Does homeostatic plasticity occur at all in adult visual cortex, and if not through synaptic scaling then through which alternative mechanism?

初级视觉皮质(V1)是哺乳动物大脑中研究最广泛的区域之一，不仅因为它对我们理解人类视觉至关重要，而且因为它已经成为研究细胞可塑性、学习和记忆过程的模型系统。儿童早期所谓关键时期的视觉体验决定了V1区神经元在一生中对视觉刺激的反应方式，任何让一只眼睛处于不利地位的情况(如对眼或白内障)，如果不及时纠正，都可能导致弱视(懒眼)。多达4%的人口患有这种疾病。近年来，越来越多的研究(包括我们自己的实验室)使用小鼠来努力发现潜在过程的细胞和分子机制，使用单眼皮缝合(单眼剥夺)作为挑战视觉皮质可塑性的标准范例。研究发现，不同的单眼剥夺时长和不同的年龄与不同的机制有关。其中之一是“稳态可塑性”，这是神经元调节其兴奋性以维持稳定的网络活动的一种重要能力，以平衡长期突触增强和抑制的影响。这被认为是由一个被称为突触缩放的过程所调节的。我们之前已经在幼年鼠的单眼剥夺后发现了这种机制运作的证据，但在成年鼠的视皮层中没有。我们还发现，AMPA受体的GluA1亚单位是视觉皮质兴奋性传递的主要媒介，对动态平衡可塑性非常重要。除了单眼剥夺，将动物置于完全黑暗中也可以触发动态平衡可塑性，可能是因为这会显著抑制整体皮质活动。最近，黑暗暴露被证明可以促进青春期大鼠和猫从单眼剥夺中恢复，因此可能提供了一个在关键期结束后治疗弱视的机会。我们实验室的最新工作表明，仅仅几天的暗暴露就可以恢复超过关键期结束的单眼剥夺小鼠V1的可塑性。这里我们讨论了关于幼年和成年小鼠体内平衡可塑性的细胞机制以及暗暴露对可塑性的影响的关键问题。我们将研究，1)黑暗暴露促进成人视皮层可塑性的机制是什么？它是使依赖于GluA1的动态平衡可塑性在幼年皮质中发挥作用，还是仅仅增强了成人可塑性的现有机制(如长时增强)？2)通过暗暴露恢复成年小鼠的视皮层可塑性在行为上有意义吗？换句话说，在一段时间的黑暗暴露后，小鼠是否在使用先前剥夺的眼睛的视觉引导任务中表现得更好？3)V1中的哪些细胞介导了GluA1依赖的可塑性？利用分子生物学技术，我们将依次抑制3种主要细胞(兴奋性锥体神经元、小白蛋白阳性抑制神经元和星形胶质细胞)中每一种细胞中GluA1的产生，以评估是否影响幼年小鼠对单眼剥夺的反应的可塑性。4)成年视皮层是否存在稳态可塑性，如果不是通过突触伸缩，那么通过哪种替代机制？

项目成果

Identification of individual PV+ cells across imaging sessions and visual responses to oriented gratings in mouse V1. from Enhancement of visual cortex plasticity by dark exposure

在小鼠 V1 的成像过程中识别单个光伏电池以及对定向光栅的视觉反应。

• DOI: 10.6084/m9.figshare.4285067
• 发表时间: 2016
• 作者: Erchova I

Experience dependent plasticity of higher visual cortical areas in the mouse.

• DOI: 10.1093/cercor/bhad203
• 发表时间: 2023-07-24
• 期刊: Cerebral cortex (New York, N.Y. : 1991)

Spatial Memory Engram in the Mouse Retrosplenial Cortex.

• DOI: 10.1016/j.cub.2018.05.002
• 发表时间: 2018-06-18
• 期刊: Current biology : CB
• 作者: Milczarek MM;Vann SD;Sengpiel F
• 通讯作者: Sengpiel F

Comparable reduction in Zif268 levels and cytochrome oxidase activity in the retrosplenial cortex following mammillothalamic tract lesions.

• DOI: 10.1016/j.neuroscience.2016.05.030
• 发表时间: 2016-08-25
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Frizzati A;Milczarek MM;Sengpiel F;Thomas KL;Dillingham CM;Vann SD
• 通讯作者: Vann SD

Enhancement of visual cortex plasticity by dark exposure.

通过黑暗暴露增强视觉皮层可塑性。

• DOI: 10.1098/rstb.2016.0159
• 发表时间: 2017-03-05
• 期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• 作者: Erchova I;Vasalauskaite A;Longo V;Sengpiel F
• 通讯作者: Sengpiel F