谷氨酸能沉默突触在视觉发育神经元可塑性中的作用

突触是神经环路中相邻神经元之间进行信息传递的点状接触区域,是神经可塑性变化的敏感部位,其中仅具有突触结构,在正常情况下不产生生理功能的突触称为沉默突触。沉默突触转化为功能性突触在神经可塑性巾具有重要作用,包括突触在形态和功能上的改变,长时程增强和长时程抑制是主要的表现模式。目前研究发现,沉默突触包括谷氨酸能沉默突触和γ-氨基丁酸能沉默突触。当前弱视发病神经机制研究的热点和前沿是视觉可塑性的研究,而后者是通过突触的修饰过程形成的。深入研究沉默突触,特别是谷氨酸能沉默突触在视觉发育过程中的作用,对于儿童弱视的治疗具有一定的临床指导意义。就近年来视觉发育可塑性中谷氨酸能沉默突触作用的研究进展进行综述。     

NMDA受体在视觉发育过程中的作用

N-甲基-D-天门冬氨酸（N—methyl—D-aspartate．NMDA）受体通过长时程增强（LTP）的建立参与了出生前后视皮质发育过程中可塑性的调控，在调节成年后视皮层神经元突触联系的可塑性中也起着关键作用，此外，NMDA受体还可诱导c—fos基因的表达。蛋白激酶C（PKC）对NMDA受体在视觉发育过程中的作用有着重要的影响。深入研究NMDA受体在视觉发育过程中的作用，对于儿童弱视的治疗具有非常重要的临床意义。     

γ-氨基丁酸A受体α1亚单位在正常发育大鼠视皮层中的表达

目的观察大鼠视皮层γ-氨基丁酸A受体（GABAAR）功能亚单位GABAARα1的表达随发育发生的量的变化。方法将45只健康纯系新生Wistar大鼠按出生后年龄以随机数字表法分为9组,每组5只,分别于出生后第0、7、14、21、28、35、45、60、90天用质量分数4%多聚甲醛经左心室穿刺至升主动脉灌注固定后处死。应用免疫组织化学染色和图像分析技术分析GABAARα1在出生后不同天龄Wistar大鼠视皮层的表达情况。结果苏木精-伊红染色显示,Wistar大鼠视皮层神经元分6层,各层神经元排列整齐。免疫组织化学染色结果显示,GABAARα1阳性反应产物呈棕黄色颗粒状,染色部位主要在神经元细胞膜、树突或轴突,其中视皮层第Ⅱ/Ⅲ层细胞染色最密集。图像分析结果提示,GABAARα1在出生时的大鼠视皮层中即已存在,但表达量很少,大鼠睁眼前表达量上升缓慢,睁眼后迅速上升,在出生时GABAARα1的吸光度（A）值为4.79±1.51,至35d峰值达231.52±21.65,差异有统计学意义（P〈0.01）,此后维持高水平至出生后90d,为231.52±21.65,与出生时比较差异有统计学意义（P〈0.01）。结论大鼠视皮层中GABAARα1表达量的发育性变化与视觉发育可塑性关键期的起始和终止在时间上具有一定的同步性,提示GABAARα1表达的发育性变化可能是视觉可塑性调节的一个重要分子基础。     

γ-氨基丁酸能神经回路在视觉系统发育和可塑性研究中的进展

研究表明γ-氨基丁酸受体及其抑制性神经回路在视觉发育和可塑性中起着至关重要的作用,近年来相关研究主要集中在GABA能抑制性回路在视觉发育关键期的开始、终止及其在成年视觉发育可塑性中的作用.本文主要回顾近年国内外在视觉发育和可塑性变化方面对γ-氨基丁酸受体及其抑制性神经回路研究的最新进展和成就,探讨影响视觉发育的机制及其与视皮层其他神经回路或结构的关系,并展望在弱视治疗中的应用前景.     

突触蛋白及其在视觉发育可塑性中的作用

突触由突触前部、突触间隙和突触后部三部分组成,突触前可塑性在神经元发育可塑性中发挥着重要作用.突触蛋白(synapsin)是一种突触前特异性蛋白家族,参与突触前短时程可塑性、长时程可塑性以及脑源性神经营养因子介导的可塑性.在视皮质,突触蛋白的含量随发育增多,异常视觉经验可影响视皮质突触蛋白的表达及磷酸化水平,表明其在视觉发育可塑性中也发挥着重要调控作用.     

PSD-95在正常发育和单眼剥夺大鼠视皮层的表达

目的研究突触后致密物(post-synaptic density,PSD)-95在正常发育以及单眼视觉剥夺性大鼠视皮层中的蛋白动态表达情况,以期在突触水平为视觉发育可塑性提供分子基础。方法健康生后14d Wistar大鼠35只,随机分成正常组及单眼剥夺组,单眼剥夺组在生后14d行单眼缝合术制备单眼剥夺模型。动物在同等环境下喂养,分别于生后14d、21d、28d、45d麻醉、灌注、固定、开颅、冠状切取后部脑组织(单眼剥夺组取剥夺眼对侧脑组织),进行常规HE和免疫组织化学方法染色。结果 HE染色中正常发育大鼠视皮层的神经元分布呈层状,且各层神经元排列整齐;单眼剥夺组大鼠视皮层未见明显异常。正常发育组PSD-95蛋白的表达随年龄呈发育性变化,生后21d有明显升高(12.47±2.06),28d(10.54±1.72)、45d(11.65±1.55)持续在较高水平。PSD-95表达产物在单眼剥夺组较正常组明显减少,生后21d(4.94±0.57)、28d(5.20±0.47)、45d(4.87±0.72)与正常组相比均下降(均为P<0.05)。结论 PSD-95可能参与视觉发育敏感期视皮层神经元可塑性的调节。     

突触自身稳态可塑性及其在视觉发育中的作用研究进展

传统的Hebbian突触可塑性可引起神经元放电与突触传递的波动,导致神经回路不同程度的失稳状态.近年研究发现的突触自身稳态可塑性能够对活动或者突触传递的波动产生一种代偿反应,使神经元放电率保持在某一功能性范围内,对保持整个神经回路的活动依赖性发育过程的稳态具有重要作用.微小兴奋性突触后电流可反映自身稳态调节过程中突触效能的动态变化.本文探讨了突触自身稳态可塑性的机制及其在视觉发育中的作用.     

神经营养素在视觉发育可塑性中的作用

越来越多的证据表明神经营养家族参与神经发育的可塑性,并对视觉发育起着至关重要的作用。本文主要回顾近年来,国内外在视觉发育和可塑性变化方面对神经营养素家族研究的最新进展和成就,探讨其影响视觉发育的机制,及与其他神经递质之间的相互作用关系,并对其在弱视治疗中的应用前景加以展望。     

视觉发育过程中神经网络的可塑性

视觉系统的神经网络是由许多神经元通过突触联系而形成的。遗传因素为年幼个体的突触联系奠定了良好的基础,而网络中的突触联系又是在内、外界环境因素的影响下,不断地发育和完善,因而突触联系便有了可塑性和敏感期,而且与一些疾病（如：弱视）的发病机理密切相关。随着电生理（尤其是膜片钳方法）和分子生物学技术的迅猛发展,近年来对这些课题进行了更深入的研究,本文综述国内外在这方面的一些新观念和所取得的新成果。     

视觉发育敏感期及其可塑性机制的研究

生后视觉发育存在"敏感期",在此期间视觉神经系统具有经验依赖的可塑性.复习文献,对视皮层NMDAR、NTs及相关基因在发育敏感期不同时限的表达规律以及视觉经验对皮层神经元突触进行修饰、重建的作用机制作一综述.     

多巴胺及其受体对形觉剥夺近视发展的影响

我国近视人口已近6亿,青少年近视率居世界第一,近视已成为危害我国居民视力健康的主要疾病之一。多巴胺是视网膜中主要的儿茶酚胺,众多研究发现提高多巴胺含量可有效抑制近视的发展。形觉剥夺是一种经典的近视造模方法,通过观察多巴胺及其受体对形觉剥夺近视发展的影响,可以反映其在近视发展中的作用,对指导控制近视的发生发展具有重要意义。本文就多巴胺及其受体对形觉剥夺性近视发展的影响进行综述,以期为近视的防治提供参考。     

Role of ocular involvement in the prediction of visual development and clinical prognosis in Aicardi syndrome.

AIMS/BACKGROUND: This study was undertaken to document visual function and acuity in patients with Aicardi syndrome, and to determine whether there is any relation between ocular features of the syndrome exhibited at birth and later visual function. METHODS: Fourteen patients with Aicardi syndrome, all examined and followed by the same ophthalmologist, were reviewed between 1975 and 1992 and their ocular characteristics and visual acuity described. It was hypothesised that larger lacunae may be associated with poorer clinical outcome and therefore the relation between these two variables was investigated. RESULTS: Visual acuity as documented by Snellen, Sheridan-Gardner, preferential looking, or pattern visual evoked potential tests was in the normal to low normal range in six eyes of four patients. Visual function correlated significantly with macular appearance. Good visual function was preserved if the fovea appeared normal on funduscopic examination and was uninvolved by lacunae. The size of the largest chorioretinal lacuna also correlated significantly with clinical outcome: patients with large lacunae were more likely to be immobile and to have no language skills. CONCLUSION: It was concluded that good visual function in patients with Aicardi syndrome may be anticipated if the fovea is normal. Although many patients have severe psychomotor retardation, the presence of predominantly small chorioretinal lacunae may indicate a better prognosis for mobility and language development.     

Spatial distribution of visual pigment and dopamine in the bullfrog retina

Visual pigments and a neurotransmitter, dopamine, were quantitatively investigated in the retina of adult bullfrog, Rana catesbeiana. The adult bullfrog (body length 15-16 cm, body weight 375 +/- 52 g, n = 10) had 21.4 +/- 4.2 nmol visual pigment and 209 +/- 28 pmol dopamine in retinal areas of 266 +/- 27 mm2. Greater pigment densities were recorded in a semicircular band around the optic disc, extending to the nasal and temporal peripheries of the ventral retina. The area with the highest concentration of visual pigment was found in the middle of the dorsal retina, 3-4 mm dorsal to the optic disc. A high concentration of vitamin A2-based pigment was found in the dorsal quarter of the retina (porphyropsin zone); the zone extended up to the most ventral part along peripheral regions of the retina. There was also a band with higher dopamine concentrations although it was not so prominent as that of the visual pigment; the highest concentration of dopamine was found in the area immediately dorsotemporal to the optic disc. Fluorescence micrography indicated that the distribution pattern of catecholamine-containing amacrine cells paralleled that of the dopamine content. The topographic map of dopamine was slightly different from that of visual pigment in the bullfrog retina.     

Advances in the development of visual prostheses

Visual prostheses are based on neuronal electrical stimulation at different locations along the visual pathway (ie, cortical, optic nerve, epiretinal, subretinal). In terms of retinal prostheses, advances in microtechnology have allowed for the development of sophisticated, high-density integrated circuit devices that may be implanted either in the subretinal or epiretinal space. Analogous to the cochlear implants for some forms of deafness, these devices could restore useful vision by converting visual information into patterns of electrical stimulation that would excite the remaining spared inner retinal neurons in patients with diseases such as retinitis pigmentosa and age-related macular degeneration. The different types of implants and recent results are discussed, but special emphasis is given to retinal implants.     

Loss of visual acuity under dopamine substitution therapy

Visual dysfunction is a well-known feature of Parkinson’s disease. Dopamine has been shown to be a functional modulator at many levels of the visual system. We report on a parkinsonian patient, suffering concurrently from various ophthalmological conditions including glaucoma and cataracts and displaying objectively measurable loss of visual acuity and blurring of vision while under medication with an MAO-B inhibitor and multiple ergolene-derived dopamine agonists. Various studies have investigated the effects of different D1- and D2-agonists and -antagonists on visual function and found that the presynaptic dopaminergic autoreceptor involved in the modulation of dopamine release in the retina displays characteristics of D2-receptors. We conclude that the observed phenomenon represents either an inhibition of dopamine release due to excessive stimulation of presynaptic D2-autoreceptors, leading to an insufficient stimulation of postsynaptic dopaminergic receptors and thus impeding retinal signal conduction, or a heretofore unclear interaction between the patient’s ophthalmological pathologies and dopaminergic therapy, possibly due to excessive stimulation of postsynaptic dopamine receptors, leading to faulty retinal information processing.     

视网膜多巴胺系统在视觉信息传递中的作用

视网膜是人体富含多巴胺的组织之一,但多巴胺在各种视功能中的作用尚不清楚.本文主要介绍视网膜组织中多巴胺细胞及其受体的分布、多巴胺神经元发育、以及多巴胺在视网膜信息传递中的可能作用.     

Role of visual cortex in interocular alignment.

The role which the visual cortex plays in the development of interocular alignment in the cat was examined by removing this structure bilaterally in 4 groups of subjects. These included (1) kittens 10 to 14 days of age, (2) 10- to 14-day-old kittens in which one eyelid was sutured shut at the same time, (3) normally reared adult cats, and (4) cats dark-reared until 4 months of age. If the cortex is removed in young kittens, interocular alignment appears to develop normally until the kittens are 60 to 80 days of age. At this time, an abrupt change in alignment resulting in incyclotorsion of the optic axes is observed. If binocular vision is prevented in kittens with neonatal visual cortex lesions by suturing one eyelid shut, convergent strabismus and/or incyclotorsion are frequently observed. This characteristic incyclotorsion does not develop if similar lesions are made in adult cats; no significant alterations of eye alignment occur in these animals even after postoperative survival times of more than 6 months. Incyclotorsion characterizes dark-reared cats when they are first brought into the light, but this diminishes with time and may even be replaced by excyclotorsion after the animals spend a few weeks in the light. If dark-reared cats are decorticated on being brought into the light, these changes are largely prevented. Such animals remain permanently incyclotorted relative to normal cats. The results indicate that the visual cortex plays an important role in the development of torsional alignment of the eyes.     

Role of a circle's center in visual interpolation

Basic geometric patterns like straight lines and circles seem fundamental to human perception and mental imagery. In this study we examined subjects' ability to interpolate circular curves-to derive the whole circle from an arc of 180 degrees or less. Specifically, we tested how the center point is utilized during such visual interpolation. Naturally, a mechanism that interpolates by extending the curvature of the visible arc will be unaffected by the presence or absence of the center point. On the other hand, a mechanism that achieves the same end by completing the circle from estimates of the center and radius will be significantly aided by the presence of the center. We found that when the visible arc was long (180 degrees), presenting the circle's center did not affect the precision with which subjects localized the invisible section. However, when the visible arc was relatively short (90 degrees or 45 degrees), displaying the center point significantly increased spatial precision. Thus, both computational mechanisms appear to exist.