Neuronal and Circuitry Mechanisms of Epileptogenesis in a Complex in Vitro Model

描述(申请人提供)：这一休假期间的目标包括：1)学习和应用一种新的复杂的体外制剂研究CMS的电路，包括癫痫的发作和扩散；2)应用成像技术了解这种复杂的体外制剂的连通性，包括代谢和内部信号成像(即NADH，IOS)；3)评估癫痫的代谢作用，特别是酮体在零镁模型中抑制癫痫发作和扩散的作用；4)与复杂癫痫综合征的临床评估和外科治疗相互作用。作为一名临床医生兼科学家，我对这个复杂的体外模型的基础神经科学感兴趣，因为我随后可以在我的资助研究中使用这种准备，以及将Bernard博士嵌入其中的相互交织的基础和临床神经科学单元。在评估了几个可能的美国休假地点后，这个位于法国马赛的地点是独一无二的，它将基础、翻译和临床神经科学/神经外科结合到一个紧密整合的单元中，专注于 关于一个临床实体，癫痫，我在几个层面上感兴趣。作为高级研究员，我打算：(A) 对研究方向进行重大改变，现在更多地侧重于癫痫，这是过去但目前没有资助的兴趣；(B)扩大我的科学和临床背景，特别是因为这个Inserm提供了截然不同的方法以及紧密交织在一起的研究/临床活动；(C)获得新的研究能力，特别是一种新的复杂的体外制剂，进一步的膜片钳记录经验，以及这种制剂的成像；以及(D)扩大我对临床癫痫领域的了解，目前在杜克大学对该领域的接触很少。作为一名神经外科医生和临床医生兼科学家，这个奖项将特别使我能够从我的常规(广泛和非常繁忙的)专业职责中抽出时间来提高我在与健康相关的癫痫研究方面的能力。由于我对基础科学、翻译和临床有广泛的兴趣，这个Inserm单位是少数几个可以很容易地增强所有这些兴趣的单位之一。例如，我对中间神经元的记录和细胞内染色以及这些中间神经元在海马区发育和维持同步性中的作用感兴趣，这非常适合伯纳德博士开创的复杂的体外准备。此外，还将回顾实验室结果在临床癫痫领域的翻译应用。这项研究与研究和分析癫痫的新方法的相关性非常高，因为这种复杂的体外准备通过保留与海马体相关的复杂电路，将简单的体外切片模型与困难的体内模型连接起来。

DESCRIPTION (provided by applicant): The goals of this sabbatical period include: 1) learn and apply a new, complex in vitro preparation to the study of circuitry in the CMS, including onset and spread of epilepsy; 2) apply imaging techniques to understand connectivity in this complex, in vitro preparation, including metabolic and intrinsic signal imaging (ie, NADH, IOS); 3) assess metabolic role of epilepsy, particularly the role of ketone bodies in suppressing epileptic onset and spread in zero magnesium model; 4) interact with the clinical assessment and surgical treatment of complex epilepsy syndromes. As a clinician-scientist I am interested in both the basic neuroscience of this complex in vitro model, since I can subsequently use this preparation in my funded research, as well as the interwoven basic and clinical neuroscience unit, in which Dr. Bernard is embedded. After assessing several possible USA sites for this sabbatical, this site in Marseille, France is unique in combining basic, translational and clinical neuroscience/neurosurgery into a tightly integrated unit, focused on a clinical entity, epilepsy, in which I am interested on several levels. As a senior fellow I intend to: (a) make a major change in research direction, focusing now more on epilepsy, a past but not currently funded interest; (b) broaden my scientific and clinical background, particularly because of the radically different approaches offered by this Inserm and the tightly interwoven research/clinical activities; (c) acquire new research capabilities, particular a new, complex in vitro preparation, further patch clamp recording experience, and imaging of this preparation; and (d) enlarge my command of the clinical epilepsy field, to which there is currently minimal exposure at Duke University. This award in particular will enable me to take time from my regular (extensive and very busy) professional responsibilities, as a neurosurgeon and clinician-scientist, to increase my capability in health-related epilepsy research. Since I have a wide variety of basic science, translational and clinical interests this Inserm unit is one of the few where all of these interests can be readily enhanced. For example, I am interested in recording and intracellular staining of interneurons and the role of these interneurons in developing and maintaining synchrony in the hippocampus, which is well suited to the complex in vitro preparation pioneered by Dr. Bernard. Also, the translational application of lab findings into the clinical epilepsy realm will be reviewed. The relevance of this research to new approaches to the study and analysis of epilepsy is very high, since this complex in vitro, preparation bridges simpler slice in vitro models with difficult in vivo models, by preserving complex circuitry relevant to the hippocampus.