Monoamine neuromodulators, e.g., dopamine (DA), norepinephrine (NE) and serotonin (5-HT), play important roles in a plethora of physiological processes, including motivational behavior, movement, attention, sleep, learning and memory. Dysfunction of the monoaminergic system is associated with a range of diseases, such as Parkinson’s disease (PD), attention deficit hyperactivity disorder, depression and addiction. A longstanding yet largely unmet goal is to measure the dynamics of monoamine neuromodulators reliably and specifically with high spatiotemporal precision, particularly in animals executing complex behaviors. In this talk I will introduce a series of genetically encoded GPCR-activation-based (GRAB) sensors that enable these measurements. GRABDA sensors can detect endogenous DA release in mouse brain slices, resolve compartmental DA release from a single neuron in live flies, and report optogenetically elicited nigrostriatal DA release as well as mesoaccumbens dopaminergic activity during sexual behavior in freely behaving mice. Using GRABNE, we successfully observed looming-evoked NE release in the midbrain of live zebrafish, as well as optogenetically and behaviorally triggered NE release in the LC and hypothalamus of freely moving mice. Similarly, GRAB5-HT can detect 5-HT release in multiple physiological and pathological conditions in both flies and mice. These sensors enrich our understanding of monoaminergic neuromodulation in the brain. Furthermore, The GRAB strategy can be applied to develop new GRAB sensors for other important neurotransmitters and neuromodulators.
Yulong Li is a professor at the School of Life Sciences of Peking University (PKU), PKU-THU Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research. He obtained his B.D. from PKU and Ph.D. from Duke Univ. He then conducted his postdoctoral research at Stanford Univ.
His group’s research centers on “synapse”, the fundamental unit for the communication between neurons. They carry two layers of research: first, they develop cutting edge research tools, namely advanced genetically-encoded imaging probes, to untangle the complexity of nervous system in space and in time; second, capitalizing on the advancement of research toolkits, they study the regulation of synaptic transmission, focusing on the modulation of various neuromodulator release. Recently, his group pioneered the development and application of new genetically-encoded fluorescent sensors, capable to detect the release of dopamine, acetylcholine, norepinephrine, and adenosine with high spatial and temporal resolution in physiological and pathological conditions. These works were recently published in Cell, Nature Biotechnology, Neuron, Nature Methods, and Nature Neuroscience. His group currently is expanding this principle to develop sensors for the entire range of known neurotransmitters and neuromodulators.