Abstract
Animal behavior is regulated by environmental stimuli and is shaped by the activity of neural networks, underscoring the importance of assessing the morpho-functional properties of different populations of cells in freely behaving animals. In recent years, a number of optical tools have been developed to monitor and modulate neuronal and glial activity at the protein, cellular, or network level and have opened up new avenues for studying brain function in freely behaving animals. Tools such as genetically encoded sensors and actuators are now commonly used for studying brain activity and function through their expression in different neuronal ensembles. In parallel, microscopy has also made major progress over the last decades. The advent of miniature microscopes (mini-microscopes also called mini-endoscopes) has become a method of choice for studying brain activity at the cellular and network levels in different brain regions of freely behaving mice. This technique also allows for longitudinal investigations while animals carrying the microscope on their head are performing behavioral tasks. In this review, we will discuss mini-endoscopic imaging and the advantages that these devices offer to research. We will also discuss current limitations of and potential future improvements in mini-endoscopic imaging.
Highlights
Understanding how brain functions are shaped by experience and, in turn, how neural networks regulate animal behavior has always been of great interest to the scientific community as well as the general public
Traditional tools used for imaging such as two-photon excitation microscopy have opened up the possibility of imaging Ca2+ activity patterns at the cellular and subcellular levels with unprecedented optical resolution
The capacity to take recordings from large neuronal populations in freely behaving animals has made it possible to analyze large-scale Ca2+ imaging data with higher statistical power and to discover different types of coding dynamics related to animal behavior
Summary
Understanding how brain functions are shaped by experience and, in turn, how neural networks regulate animal behavior has always been of great interest to the scientific community as well as the general public. In addition to combining imaging and electrophysiological recordings, commercially available dual implant baseplates composed of a GRIN lens and an optical fiber allow Ca2+ imaging and photometry recordings in two different brain regions located as close together as 1 mm to be performed Another potential new application for mini-endoscopes involves combining Ca2+ imaging with intrinsic optical signals (Senarathna et al, 2019). The first versions of commercial and open-source mini-endoscopes offered the possibility to manually and mechanically adjust the image focus with a slider, screw, or turret before starting a recording, which resulted in additional manipulations of both the device and the animal (Ghosh et al, 2011; Barbera et al, 2016; Cai et al, 2016; Liberti et al, 2017; Jacob et al, 2018) To deal with this issue, updated electronically focused versions of endoscopes have been released by several companies such as Inscopix and Doric Lenses or were built from open-source designs (e.g., UCLA miniscope version 4). Future studies will certainly deepen our understanding of the cellular and molecular mechanisms operating in homeostatic and diseased conditions
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