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Implantable graded‐index fibers for neural‐dynamics‐resolving brain imaging in awake mice on an air‐lifted platform

We demonstrate a versatile framework for cellular brain imaging in awake mice based on suitably tailored segments of graded‐index (GRIN) fiber. Closed‐form solutions to ray‐path equations for graded‐index waveguides are shown to offer important insights into image‐transmission properties of GRIN fibers, suggesting useful recipes for optimized GRIN‐fiber‐based deep‐brain imaging. We show that the lengths of GRIN imaging components intended for deep‐brain studies in freely moving rodents need to be chosen as a tradeoff among the spatial resolution, the targeted imaging depth and the degree of fiber‐probe invasiveness. In the experimental setting that we present in this paper, the head of an awake mouse with a GRIN‐fiber implant is fixed under a microscope objective, but the mouse is free to move around an in‐house‐built flat‐floored air‐lifted platform, exploring a predesigned environment, configured as an arena for one of standard cognitive tests. We show that cellular‐resolution deep‐brain imaging can be integrated in this setting with robust cell‐specific optical neural recording to enable in vivo studies with minimal physical restraints on animal models. The enhancement of the information capacity of the fluorescence signal, achieved via a suitable filtering of the GRIN‐fiber readout, is shown to open routes toward practical imaging modalities whereby the deep‐brain neuronal dynamics and axonal connections underpinning the integrative functions of essential brain structures can be studied in awake rodent models.