Circuit Investigations With Open-Source Miniaturized Microscopes: Past, Present and Future

Abstract

The ability to simultaneously image the spatiotemporal activity signatures from many neurons during unrestrained vertebrate behaviors has become possible through the development of miniaturized fluorescence microscopes, or miniscopes, sufficiently light to be carried by small animals such as bats, birds and rodents. Miniscopes have permitted the study of circuits underlying song vocalization, action sequencing, head-direction tuning, spatial memory encoding and sleep to name a few. The foundation for these microscopes has been laid over the last two decades through academic research with some of this work resulting in commercialization. More recently, open-source initiatives have led to an even broader adoption of miniscopes in the neuroscience community. Open-source designs allow for rapid modification and extension of their function, which has resulted in a new generation of miniscopes that now permit wire-free or wireless recording, concurrent electrophysiology and imaging, two-color fluorescence detection, simultaneous optical actuation and read-out as well as wide-field and volumetric light-field imaging. These novel miniscopes will further expand the toolset of those seeking affordable methods to probe neural circuit function during naturalistic behaviors. Here, we will discuss the early development, present use and future potential of miniscopes.

Simultaneous Electrophysiology and Fiber Photometry in Freely Behaving Mice

“…A limitation of fiber photometry in general is that it provides only population-level activity. Although an alternative approach is the use of GRIN lenses (Ghosh et al, 2011;Skocek et al, 2018;Aharoni and Hoogland, 2019), this approach is more invasive due to larger lens diameters. Hence, simultaneous calcium imaging of individual neurons and electrophysiological monitoring may be challenging.…”

The McGill-Mouse-Marmoset Platform: A Standardized Approach for High-throughput Imaging of Neuronal Dynamics During Behavior

“…Currently, the one-photon, wide-field miniscope is ideal for high throughput imaging in freely behaving animals as it is the most cost-efficient, lightweight, and robust version of the miniscopes developed to date, with a large field of view to maximize cell counts 15 . However, recent initiatives in open source development of miniscopes pave the way for a multitude of independently designed and modified miniscopes in the near future, with a variety of unique uses 33 . These include integration with optogenetic manipulations 34 and wire-free miniscopes for efficient monitoring of social behaviour 35 .…”

Online analysis of microendoscopic 1-photon calcium imaging data streams

“…In vivo calcium imaging of activities from large neural populations at single cell resolution has become a widely used technique among experimental neuroscientists. Recent advances in optical imaging technology using a 1-photon-based miniscope and a microendoscopic lens have enabled in vivo calcium imaging studies of neural activities in freely behaving animals [1][2][3]. However, this data typically displays large, blurry background fluctuations due to fluorescence contributions from neurons outside the focal plane, arising from the large integration volume of one photon microscopy.…”