A New Model of Gestational Cannabis Exposure

摘要 在过去十年中，怀孕期间使用大麻的人数急剧增加。 虽然大麻及其成分对大脑发育的影响鲜为人知， 最近的研究发现，母亲的子女经常出现心理健康问题 在怀孕期间吸食大麻。在人类妊娠的第三个三个月，大脑 经历了一个以突触形成的密集过程为特征的“生长激增”。 这一阶段之后是活动依赖的神经元可塑性的精细化阶段，其中 达到“正确目标”的突触得到加强，而达到“不正确目标”的突触得到加强 目标“被修剪掉。在此期间接触药物和某些药物会对 有可能改变这些过程，导致多种神经行为问题。一直以来 在人类和动物模型中证明，发育中的THC暴露降低了 CB1R的表达。在视皮层的2/3层中，内源性大麻类神经传递是 ILTD的表达和从高到低的发育转变 该区域成熟抑制性细胞的GABA释放概率特征。适当的水平 抑制对眼优势可塑性和神经元的建立是必不可少的 负责神经元定向调节和定向选择性形成的电路 柱子。基于这一科学前提，我们假设在第三次接触中 相当于人类妊娠的三个月导致内源性大麻素持续减少 传递，导致iLTD受损，阻止成熟的抑制。作为一名 结果，眼优势可塑性和定向选择性都会受到损害。 在这里，我们将使用体内和体外电生理学和光学成像的组合 检验这一假说的内在信号。这些实验的完成将导致 在开发一种新的产前大麻暴露模式方面，该模式可用于 研究妊娠大麻的作用机制和可能的干预措施。

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.