![]() ![]() Calcium imaging relies on the usage of high resolution genetically encoded calcium indicators (GECIs) (e.g., GCaMP), which detect calcium-dependent changes in the chromophore environment of ultrasensitive circularly permuted fluorescent proteins (cpFP) (e.g., the green cpGFP). Advanced in vivo imaging methods to track AP propagation in genetically defined cells have been developed across the past decades, most notably in vivo calcium imaging, the method of choice for monitoring intracellular calcium levels as a proxy for AP propagation. The ability to answer these questions is dependent on available technologies that can reliably monitor neuromodulatory processes, including (i) action potential (AP) propagation and (ii) synaptic release. A key challenge for neuroscientists is the ability to understand how neuromodulators encode and control behavioral outputs in health and disease states and in turn how these neuromodulators can be harnessed to treat brain disorders. Disturbances in neuromodulatory signaling pathways are associated with a large number of behavioral dysfunctions and brain pathologies including psychotic and mood disorders, motor diseases or addiction. By rapidly modifying the properties of their target neurons, neuromodulators can deeply affect neural circuits and in turn modulate behavior. Neuromodulators, such as dopamine (DA), provide one evolutionary conserved mechanism that supports this behavioral adaptability. Measuring Neuromodulator Release During BehaviorĪnimals must constantly adjust their behavior to meet the demands of ever-changing sensory inputs, external environments and internal needs. Altogether this review should act as a tool to guide DA sensor choice for end-users.ġ.1. We then outline a map of DA heterogeneity across the brain and provide a guide for optimal sensor choice and implementation based on local DA levels and other experimental parameters. In this review, we use DA as an example we briefly summarize old and new techniques to monitor DA release, including DA biosensors. Molecular specificity, sensor kinetics, spectral properties, brightness, sensor scaffold and pharmacology can further influence sensor choice depending on the experimental question. Sensor properties, most importantly their affinity and dynamic range, must be carefully chosen to match local DA levels. When implementing these tools in the laboratory, it is important to consider there is not a ‘one-size-fits-all’ sensor. Combined with rapid developments in in vivo imaging, these sensors have the potential to transform the field of DA sensing and DA-based drug discovery. Recently, red and green genetically encoded sensors for DA (dLight, GRAB-DA) were developed and now provide the ability to track release dynamics at a subsecond resolution, with submicromolar affinity and high molecular specificity. Understanding how dopamine (DA) encodes behavior depends on technologies that can reliably monitor DA release in freely-behaving animals. ![]()
0 Comments
Leave a Reply. |