Flexible fiber bundle devices for chronic imaging across deep brain regions in mice

Capturing neural activity across deep brain regions is highly motivated by the need to understand how distributed circuits coordinate complex behaviors and brain functions. Optical access to such regions in animal models is achievable using endoscopic probes; however, implantable (graded refractive index) lenses are mechanically incompatible with soft brain tissue and difficult to scale across sites of interest. Alternatively, we present devices incorporating soft polymer optical fiber bundles as flexible alternatives capable of spatially resolving neuronal activity while incurring less damage to brain tissue. Critically, we combine our fiber bundles with 3D-printed housing and viral vector delivery to enable chronic calcium imaging across three deep brain regions with a single back-end microscope. Our results show coordinated and heterogeneous activity along midbrain sites related to stress and reward in response to drug delivery, which we hope will yield new insights into the biology of addiction.