Neuromodulation and Plasticity of the Visual System

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My NSERC program is to determine the role of neuromodulators in the plasticity and functioning of the visual system. In this proposal, I will specifically study the contribution of the endocannabinoid (eCB) system in properties of visual neurons at different levels. eCB plays a modulatory role in neurobiological functions such as memory, nociception, plasticity, and in a number of cellular signaling processes. eCBs are generally associated with the modulation of neuronal transmission and with developmental processes. These effects depend largely on two cannabinoid receptors, CB1 (CB1R) and CB2 (CB2R). Both subtypes have been found in the central nervous system, including the visual system. For example, CBRs are present in all major types of retinal neurons, in neurons of the lateral geniculate nucleus (LGN) and of the visual cortex (V1). While these observations indicate that an eCB signaling system exists in the visual system, there is little information, if any, about the functional impact of cannabinoids on visual neuron properties. Given the eCBs widespread distribution in cerebral structures of the visual system, eCBs have the potential to affect both vision and visual behavior. In this proposal, I plan to pursue my investigation on the functional role of cannabinoids in vision using complementary approaches (e.g. electroretinogram, single cell recording, and optical imaging). I propose three specific aims: The first aim is to determine the contribution of the cannabinoid system in the retinal function by studying the effects of exogenous agonists and antagonists of CBRs on the scotopic and photopic responses as well as on the ON and OFF pathways of adult rodents. In conjunction with these experiments, we will assess the effects of eCBs using inhibitors of their synthesis or degradation enzymes. The second aim is to determine the consequences of the eCB-mediated retinal changes (characterized in aim 1) on thalamic and cortical processing using visual evoked potentials, brain optical imaging and single-cell recordings. The third aim is to investigate the direct and local impact of eCBs in the LGN and V1. CBR ligands or enzyme inhibitors will thus be injected in the two structures to assess the influence of endocannabinoids on the neural coding of visual stimuli at central levels. First, the effects of solely modulating LGN activity on cortical processing will be assessed. Then, the effects of administrating eCBS at the cortical level on the comprising neurons will be studied. The proposed experiments are essential for a better understanding of the fundamental role of the eCB system in normal visual processing. These unique and innovative experimental approaches will address different levels of visual system functions with complementary methodological approaches, and I believe that they represent the first necessary step to reveal the functional role of eCBs on processes such as receptive field formation and temporal visual coding.