Fetal Alcohol Exposure and Sensorimotor Cortex Function

描述(申请人提供)：怀孕期间大量饮酒的母亲的孩子会出现发育迟缓、语言和学习障碍，以及视觉空间和感觉运动能力受损，包括平衡不良和粗大/精细运动协调。这一范围的缺陷突显了胎儿酒精暴露(FAE)时中枢神经系统(CNS)处理的中断。在人类中，这种中枢神经系统残疾会对生活质量产生负面影响。我们对FAE对中枢神经系统加工的影响的不完全了解限制了我们改善这些缺陷的能力。通过使用我们擅长的模型系统和技术，我们将阐明FAE在感觉运动系统中造成的特定干扰，并测试潜在的机制。通过了解与感觉运动功能相关的酒精相关神经异常的生物学基础，我们可以希望改进FAE受损儿童的康复训练策略。 我们将检验FAE改变躯体感觉皮质和运动皮质的组织以及这些区域之间信息传递的途径的假设。我们将研究FAE后感觉运动障碍的可能机制。成年大鼠的感觉运动系统将作为我们的模型系统。我们将利用躯体感觉皮层中与前爪表征相关的中枢神经系统加工，研究前肢在运动皮质中的表征和运动研究的输出通路，以及前肢感觉和运动皮质之间的通路，以进行感觉运动整合研究。我们之前已经研究了新生和成年大鼠的躯体感觉皮质，以及小鼠运动皮质的功能组织，这为拟议的研究提供了基础。该提案结合了我们实验室中常规使用的结构和功能图谱、体内细胞内记录和标记、微刺激、解剖示踪、免疫细胞化学和电子显微镜等技术。特定的目标将FAE大鼠与配对喂养、全食和交叉养育的对照组大鼠进行比较。

DESCRIPTION (provided by applicant): Children of mothers who consume significant amounts of alcohol during pregnancy exhibit delayed development, deficits in language and learning, and impaired visuospatial and sensorimotor abilities, including poor balance and gross/fine motor coordination. This range of deficits underscores a disruption of central nervous system (CNS) processing in fetal alcohol exposure (FAE). In humans, such CNS disabilities negatively impact quality of life. Our incomplete understanding of the effects of FAE on CNS processing limits our ability to ameliorate these deficits. By using a model system and techniques in which we are expert, we will elucidate the specific disruptions caused by FAE in sensorimotor systems and test potential mechanisms. By understanding the biological bases of alcohol-related neurological abnormalities related to sensorimotor functions, we can hope to achieve improved training strategies for rehabilitation in FAE-impaired children. We will test the hypothesis that FAE alters the organization of somatosensory cortex and motor cortex and the pathway for the transfer of information between these regions. We will examine potential mechanisms for sensorimotor deficits following FAE. The sensorimotor system in adult rats will serve as our model system. We will study CNS processing using the well-characterized forepaw barrel subfield (FBS) in somatosensory cortex associated with the representation of the forepaw for somatosensory investigations, the forelimb representation in motor cortex and the output pathway for motor investigations, and the pathway between forelimb sensory and motor cortices for sensorimotor integration studies. We have previously studied somatosensory cortex in newborn and adult rats and the functional organization of mouse motor cortex that provide foundations for the proposed studies. The proposal incorporates techniques for structural and functional mapping, in-vivo intracellular recording and labeling, microstimulation, anatomical tracing, immunocytochemistry, and electron microscopy that are routinely used in our laboratories. Specific Aims will compare FAE rats with pair-fed, chow-fed, and cross-fostered control rats.