Spatio-temporal firing dynamics of cortical and thalamic neurons during typical absence seizures

失神癫痫不同于流行的癫痫图像，因为它的发作不伴有抽搐或其他主要的运动和行为体征。事实上，在较温和的形式下，失神发作可能只是由突然而短暂的意识中断组成(即患者看起来像是失神？从周围活动)和一些轻微的面部、手臂或腿部运动，解释了为什么直到上个世纪中叶，这种疾病在很大程度上还没有被发现，而且往往没有被认为是一种适当的神经系统疾病。失神癫痫是一种遗传性疾病，可发生在年仅2岁的儿童中。在较轻的病例中，癫痫发作可能在青少年后期自发消失，但在绝大多数严重病例中，癫痫每天可发生多达200次，并伴有或发展为惊厥性癫痫。虽然有一些药物能够消除或减少每日失神发作的频率，但这些药物的使用并不是对所有患者都有效，而且与一些不想要的副作用(特别是儿童)有关，对育龄妇女是不可取的。虽然全世界都欢迎对有癫痫发作史的家庭的伴侣进行主动咨询，但我们治愈这一疾病从而减少其教育、发展和经济负担的能力，由于导致这一疾病的大量不同基因突变，以及我们对导致这些癫痫表现的错综复杂的大脑变化缺乏了解，而变得更加困难。这个项目的目的是描述大脑中不同类型的特殊细胞(称为神经元)之间的通信如何在失神发作期间改变它们的电活动。我们将集中在大脑的两个区域(称为皮质和丘脑)，这两个区域已经被癫痫患者的非侵入性成像显示为失神发作起源的关键区域。此外，我们将研究钙离子通过这些神经元中特定的毛孔是否对启动导致失神发作的异常电事件具有重要意义。这项研究可能会为失神癫痫的治疗干预开辟新的途径，并部分填补由于与老年神经系统疾病相比，治疗这种疾病的新药市场规模较小而缺乏私营部门支持所留下的空白。

Absence epilepsy is different from the popular image of epilepsy, since its seizures are not accompanied by convulsions or other major motor and behavioural signs. In its milder forms, in fact, an absence seizure may simply consists of a sudden and brief interruption of consciousness (i.e. the sufferer appears to be ?absent? from surrounding activities) and some minor facial, arm or leg movements, explaining why almost up to the middle of the last century this disease went largely undetected and often unrecognized as a proper neurological disease. Absence epilepsy is a genetic condition that can occur in children as young as 2 years of age. In milder cases, seizures may spontaneously disappear in the late teens, but in the vast majority of severe cases they can occur up to 200 times per day, and are accompanied, or develop into, convulsive epilepsy. Whereas there are medicines capable of abolishing or reducing the daily frequency of absence seizures, their use is not effective in all sufferers, is associated with a number of unwanted side-effects (particularly in children), and is not advisable in women of child-bearing age. While pro-active counselling of partners from families with a history of absence seizures has been welcome worldwide, our ability to cure this disease, and thus to reduce its educational, developmental and financial burden, is compounded by the large number of different genetic mutations that are responsible for this disease and by our poor understanding of the intricate brain alterations that lead to the expression of these seizures. This project, will aim to characterize the way communications between different types of specialized cells in the brain (called neurons) alter their electrical activities during absence seizures. We will focus on two areas of the brain (called the cortex and the thalamus) that have been shown by non-invasive imaging of epileptic patients to be the key regions where absence seizures originate. Moreover, we will investigate whether the passage of calcium ions through specific pores in these neurons is of importance for setting in motion the abnormal electrical events that lead to absence seizures. This research will potentially lead to novel avenues of therapeutic intervention for absence seizures, and partly fill the gap left by the lack of support from the private sector due to the small size of the market for novel drugs for this disease compared to the neurological disorders of old age.