The endocannabinoid system in the monkey visual brain.

猴子视觉大脑中的内源性大麻素系统。

• 批准号: RGPIN-2017-03898
• 负责人: Ptito, Maurice
• 金额: $ 2.04万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630737
• 关键词: endocannabinoid; system; monkey; visual; brain.

During the last tenure of the grant, we produced novel and groundbreaking results on the expression, localization and function of the endocannabinoid system in the monkey retina. Monkeys have a very similar visual system to humans and this makes it a rather interesting species to study vision and hence extrapolate data to humans. We have shown unequivocally that the cannabinoid receptors are expressed in specific retinal components and might contribute to diverse visual functions. The cannabinoid receptor 1 (CB1) is mainly expressed in the cone photoreceptors of the central retinal whereas the cannabinoid receptor 2 (CB2R) is mainly found in the retinal glia (Müller cells). The third putative endocannabinoid, GPR55, is expressed in the rod photoreceptors. The contribution of these receptors types to retinal function was assessed through their action on the electroretinographic waves (ERG). Through intravitreous injections of agonists or blockers of the receptors, we were able to show their different modulatory influences on the photopic and scotopic ERG waves. The question remains however on where these cannabinoid receptors are expressed upstream in the retino-recipient structures mainly the primary (dorsal Lateral geniculate nucleus of the thalamus) and the secondary (Superior colliculus-Pulvinar) subcortical relays and the associated cortical recipient areas such the striate cortex (area V1) and the extrastriate cortices (V2 and V3). We will also investigate the expression of these receptors in the efferent dorsal (e.g. area hMT+) and ventral (e.g. inferotemporal) cortical visual streams. The expression and localization of the cannabinoid receptors will be measured with immunohistochemical methods that are currently used in our laboratory. The functions of the cannabinoid receptors on higher visual functions will be investigated using electrophysiological techniques like the Visually Evoked Cortical Potentials (VECP) and pattern electroretinographic responses (PERG) that are good measures of visual acuity and contrast sensitivity with the added advantage that these techniques are totally non-invasive and can be obtained on anesthetized preparations. Selective agonists or blockers of the endocannabinoid receptors will highlight their relative contribution to the M (magnocellular) and P (parvocellular) pathways through their modulatory effects on the visually evoked response patterns. Finally, in vivo measures of visual functions (e.g. visual acuity, contrast sensitivity, optokinetic nystagmus, motion) will be assessed using behavioral techniques that do not require lengthy training such as those currently used in human infants like preferential looking. The results of the proposed project are of great importance for the understanding of the mechanisms by which cannabis sativa exerts its function on the visual system and hence on vision.

在该基金的最后一个任期内，我们在猴子视网膜内源性大麻素系统的表达、定位和功能方面取得了突破性的新成果。猴子的视觉系统与人类非常相似，这使得猴子成为研究视觉的一个相当有趣的物种，从而将数据外推到人类身上。我们已经明确表明大麻素受体在特定的视网膜成分中表达，并可能有助于不同的视觉功能。大麻素受体1 （cannabinoid receptor 1, CB1）主要表达于视网膜中央锥体感光细胞，而大麻素受体2 （cannabinoid receptor 2, CB2R）主要表达于视网膜胶质细胞（m<s:1> ller细胞）。第三种内源性大麻素，GPR55，在杆状光感受器中表达。这些受体类型对视网膜功能的贡献是通过它们对视网膜电波（ERG）的作用来评估的。通过玻璃体内注射受体的激动剂或阻滞剂，我们能够显示它们对光性和暗性ERG波的不同调节作用。然而，问题仍然是这些大麻素受体在视网膜受体结构的上游何处表达，主要是初级（丘脑的背外侧束核）和次级（上丘-枕核）皮层下继电器以及相关的皮层受体区域，如纹状皮层（区域V1）和纹状外皮层（区域V2和V3）。我们还将研究这些受体在传出背侧（例如hMT+区域）和腹侧（例如颞下）皮层视觉流中的表达。大麻素受体的表达和定位将使用我们实验室目前使用的免疫组织化学方法进行测量。大麻素受体在高级视觉功能上的功能将使用电生理技术进行研究，如视觉诱发皮质电位（VECP）和模式视网膜电图反应（PERG），这些技术是视觉灵敏度和对比灵敏度的良好测量，其额外的优势是这些技术完全无创，可以在麻醉制剂上获得。内源性大麻素受体的选择性激动剂或阻滞剂将通过其对视觉诱发反应模式的调节作用，突出其对M（大细胞）和P（细细胞）途径的相对贡献。最后，将使用不需要长时间训练的行为技术来评估体内视觉功能（如视力、对比敏感度、光动性眼球震颤、运动），这些技术目前用于人类婴儿，如优先注视。该项目的结果对于理解大麻对视觉系统和视觉系统发挥其功能的机制具有重要意义。