High-throughput DNA sequencing method for probing the connectivity of neural circ

描述(申请人提供)：大脑是一个极其复杂的网络，由数万亿个突触连接的数十亿个神经元组成。这些连接的细节--哪些神经元与其他神经元形成突触连接--在决定大脑功能方面至关重要。出生前和出生后早期发育过程中这些连接的畸形可能会导致智力低下、自闭症或精神分裂症；晚年特定连接的丢失与阿尔茨海默氏症等神经退行性疾病有关。确定大脑接线图的有效方法将改变神经科学研究。我们建议开发一种方法，利用高通量DNA测序来探测单个神经元分辨率下神经电路的连通性。 公共卫生相关性：许多神经精神疾病和神经退行性疾病，包括自闭症、精神分裂症、精神发育迟滞和阿尔茨海默病，都会导致大脑中特定连接的丧失。我们建议开发一种在疾病动物模型中识别这些联系的方法。我们的方法将对理解这些疾病的原因产生深远的影响。

DESCRIPTION (provided by applicant): The brain is an extremely complex network, consisting of billions of neurons connected by trillions of synapses. The details of these connections-which neurons form synaptic connections with which other neurons-are crucial in determining brain function. Malformation of these connections during prenatal and early postnatal development can lead to mental retardation, autism or schizophrenia; loss of specific connections later in life is associated with neurodegenerative diseases such as Alzheimer's. An efficient method for determining the brain's wiring diagram would transform neuroscience research. We propose to develop a method for exploiting high-throughput DNA sequencing to probe the connectivity of neural circuits at single-neuron resolution. PUBLIC HEALTH RELEVANCE: Many neuropsychiatric and neurodegenerative diseases, including autism, schizophrenia, mental retardation and Alzheimer's disease, result in the loss of specific connections in the brain. We propose to develop a method for identifying these connections in animal models of disease. Our method will have a profound impact on understanding the causes of these diseases.