A New Model of Gestational Cannabis Exposure

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Summary The use of cannabis during pregnancy have dramatically increased during the last ten years. While the effects of cannabis and its components on brain development are poorly known, recent studies have observed frequent mental health problems in the offspring of mothers that used marijuana during gestation. During the third trimester of human gestation the brain undergoes a “growth spurt” that is characterized by an intensive process of synaptogenesis. This stage is followed by a period of refinement by activity-dependent neuronal plasticity where synapses reaching “correct targets” are strengthened whereas synapses reaching “incorrect targets” are pruned. The exposure to drugs and certain medications during this period have the potential to alter these processes, resulting in multiple neurobehavioral problems. It has been demonstrated in humans and animal models that developmental THC exposure reduces the expression of CB1r. In layer 2/3 of the visual cortex endocannabinoid neurotransmission is essential for the expression of iLTD and for the developmental transition between high to low GABA release probability characteristic of mature inhibitory cells in this region. Proper levels of inhibition are essential for the ocular dominance plasticity and the establishment of neuronal circuits responsible for neuronal orientation tuning and formation of orientation selectivity columns. Based on this scientific premise we hypothesize that THC exposure during the third trimester equivalent of human gestation leads to persistent reduction in endocannabinoid transmission, resulting in an impairment in iLTD and preventing maturation of inhibition. As a consequence, both ocular dominance plasticity and orientation selectivity would be impaired. Here we will use a combination of in vivo and ex vivo electrophysiology and optical imaging of intrinsic signals to test this hypothesis. The accomplishment of these experiments would result in the development of a novel model of prenatal exposure to cannabis that could be used to investigate mechanisms of action of gestational marijuana and potential interventions.