The endocannabinoid system in the monkey visual brain.

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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.