Department of Biochemistry and Molecular Medicine and ‡Center for Neuroscience, University of California Davis , Davis, California 95817, United States.
ACS Chem Neurosci. 2015 Jan 21;6(1):84-93. doi: 10.1021/cn500280k. Epub 2015 Jan 13.
A major challenge in neuroscience is to decipher the logic of neural circuitry and to link it to learning, memory, and behavior. Synaptic transmission is a critical event underlying information processing within neural circuitry. In the extracellular space, the concentrations and distributions of excitatory, inhibitory, and modulatory neurotransmitters impact signal integration, which in turn shapes and refines the function of neural networks. Thus, the determination of the spatiotemporal relationships between these chemical signals with synaptic resolution in the intact brain is essential to decipher the codes for transferring information across circuitry and systems. Here, we review approaches and probes that have been employed to determine the spatial and temporal extent of neurotransmitter dynamics in the brain. We specifically focus on the design, screening, characterization, and application of genetically encoded indicators directly probing glutamate, the most abundant excitatory neurotransmitter. These indicators provide synaptic resolution of glutamate dynamics with cell-type specificity. We also discuss strategies for developing a suite of genetically encoded probes for a variety of neurotransmitters and neuromodulators.
神经科学的一个主要挑战是破译神经回路的逻辑，并将其与学习、记忆和行为联系起来。突触传递是神经回路中信息处理的关键事件。在细胞外空间，兴奋性、抑制性和调制性神经递质的浓度和分布影响信号整合，进而塑造和完善神经网络的功能。因此，确定这些化学信号与完整大脑中突触分辨率之间的时空关系对于破译跨越回路和系统传递信息的代码至关重要。在这里，我们回顾了用于确定大脑中神经递质动力学的空间和时间范围的方法和探针。我们特别关注直接探测谷氨酸（最丰富的兴奋性神经递质）的基因编码指示剂的设计、筛选、表征和应用。这些指示剂提供了具有细胞类型特异性的谷氨酸动力学的突触分辨率。我们还讨论了开发一系列用于各种神经递质和神经调质的基因编码探针的策略。
