SPLTRAK Abstract Submission
Imaging During Odor-Guided Behavior With a Novel, Wide Field-of-View Miniature Fluorescence Microscope
Daniel P. Leman1, Ichun A. Chen1, William W. Yen1, Lewis N. Perkins1, William A. Liberti III2, Kivilcim Kilic1, Alberto Cruz-Martin1, Timothy J. Gardner1,3, Timothy M. Otchy1, Ian G. Davison1
1Boston University, Boston, MA, United States
2University of California, Berkeley, Berkeley, CA, United States
3Neuralink, San Francisco, CA, United States

Odors provide a rich set of environmental cues that guide ethologically relevant behaviors such as localization, navigation, and social interactions with both conspecifics and predators.  Many, if not all, of these contexts require animals to freely explore and actively sample their surroundings in both space and time. The development of miniaturized, head-mounted fluorescence microscopes, or “miniscopes”, combined with advances in genetically encoded Ca2+ indicators, has allowed recording of activity of large neural populations in small animals during diverse naturalistic behaviors. However, current miniscope systems rely on small diameter gradient-index optics that restrict their effective imaging areas to less than 1 mm2. Here, we present an enlarged field-of-view miniscope providing optical access to brain areas encompassing approximately 7-8 mm2, an order of magnitude increase over prior systems for freely behaving mice. Our optical design provides resolution of approximately 10 μm, sufficient for resolving individual neurons.  Our low-cost, open source system is based on a 3D-printed housing and off-the-shelf components, and is readily modifiable for different experimental demands.  Here we use the wide-area miniscope to image sensory maps in the main olfactory bulb of mice engaged in an odor-based localization task, revealing both spatial patterns of glomerular responses and temporal dynamics of sniffing-coupled activity. This system promises to help provide insight into the strategies that underpin natural sensory behaviors.  More broadly, it will also allow visualization of extended cortical regions, providing a valuable approach for probing large-scale cross-area interactions in naturalistic environments.