Design of Molecular Probes For Optical Imaging of Dopamine Neurotransmission

描述（申请人提供）：多巴胺（DA）神经传递在学习，动机和奖励过程以及工作记忆和认知中起关键作用。突触前多巴胺储存和释放的异常是多种神经精神疾病的基础，包括精神分裂症、多动症、药物成瘾和帕金森病。PI的实验室与David Sulzer博士的实验室合作，最近推出了一种名为“荧光假神经递质”（ffn）的新型光学探针，这种探针被设计为多巴胺的示踪剂，可以直接可视化神经递质在单个突触末端的摄取和释放。ffn提供了第一种光学成像大脑中神经递质释放的手段，从而能够检查与发病机制和治疗作用相关的突触可塑性。新的ffn将被合成以优化这些探针的关键功能参数，包括摄取选择性、信号对比、诱发释放动力学和光稳定性。此外，还将开发pH响应型ffn。这些目标将通过有前途的化合物引线的系统结构改变来实现。

DESCRIPTION (provided by applicant): Dopamine (DA) neurotransmission plays key roles in learning, motivation and reward processes as well as working memory and cognition. Aberrations in presynaptic dopamine stores and release underlie several neuropsychiatric disorders including schizophrenia, ADHD, drug addiction and Parkinson's disease. The PI's laboratory in collaboration with the laboratory of Dr. David Sulzer recently introduced new optical probes termed "Fluorescent False Neurotransmitters" (FFNs) that were designed as tracers of dopamine to enable direct visualization of neurotransmitter uptake and release at individual synaptic terminals. FFNs provide the first means to optically image the neurotransmitter release in the brain and thus enable the examination of synaptic plasticity associated with pathogenesis and the action of therapeutics. New FFNs will be synthesized to optimize the key functional parameters of these probes, which include the selectivity of uptake, signal contrast, kinetics of evoked release, and photostability. Also, pH responsive FFNs will be developed. These aims will be achieved via systematic structural alterations of promising compound leads.