Chronic multiscale resolution of mouse brain networks using combined mesoscale cortical imaging and subcortical fiber photometry

SIGNIFICANCE: Genetically encoded optical probes to image calcium levels in neurons in vivo are used widely as a real-time measure of neuronal activity in the brain. Mesoscale calcium imaging through a cranial window provides a method of studying the interaction of circuit activity between cortical areas but lacks access to subcortical regions. AIM: We have developed an optical and surgical preparation that preserves wide-field imaging of the cortical surface while also permitting access to specific subcortical networks. APPROACH: This was achieved using an optical fiber implanted in the striatum, along with a bilateral widefield cranial window, enabling simultaneous mesoscale cortical imaging and subcortical fiber photometry recording of calcium signals in a transgenic animal expressing GCaMP. Subcortical signals were collected from the dorsal regions of the striatum. We combined this approach with multiple sensory-motor tasks, including specific auditory and visual stimulation, and video monitoring of animal movements and pupillometry during head-fixed behaviors. RESULTS: We found high correlations between cortical and striatal activity in response to sensory stimulation or movement. Furthermore, spontaneous activity recordings revealed that specific motifs of cortical activity are correlated with presynaptic activity recorded in the striatum, enabling us to select for corticostriatal activity motifs. CONCLUSION: We believe that this method can be utilized to reveal not only global patterns but also cell-specific connectivity that provides insight into corticobasal ganglia circuit organization.