A compact head-mounted endoscope for in vivo calcium imaging in freely-behaving mice

Miniaturized fluorescence microscopes for imaging calcium transients are a promising tool for investigating the relationship between behaviour and population-level neuronal activity in rodents. However, commercially available miniature microscopes may be costly, and, because they are closed-source, may not be easily modified based on particular experimental requirements. Here, we describe how to build and use a low-cost c ompact h ead-mounted e ndoscope (CHEndoscope) system for in vivo calcium imaging. The CHEndoscope uses an implanted gradient index (GRIN) lens along with the genetically encoded calcium indicator GCaMP6 to image calcium transients from hundreds of neurons simultaneously in awake behaving mice. This system is affordable, open-source, and flexible, permitting modification depending on the particular experiment. This Unit describes in detail the assembly, surgical implantation, data collection, and processing of calcium signals using the CHEndoscope system. The aim of this open framework model is to provide an accessible set of miniaturized calcium imaging tools for the neuroscience research community. Significance Statement The ability to image calcium transients in awake, behaving rodents using miniature microscopes opens exciting and novel avenues for gaining insights into how information is encoded in neural circuits. The development of this tool has already had a significant impact on neuroscience research. The cost of commercial systems, however, may be prohibitive for many laboratories. Here, we describe an affordable, open-source c ompact h ead-mounted e ndoscope (CHEndoscope) system for performing in vivo calcium imaging in freely-behaving mice. CHEndoscopes may be manufactured by individual laboratories at relatively minor cost. Our hope is that greater availability of affordable, open-source tools (such as the one presented here) will accelerate the pace of discoveries in systems neuroscience.