High-density multi-fiber photometry for studying large-scale brain circuit dynamics

Animal behavior originates from neuronal activity distributed and coordinated across brain-wide networks. However, techniques to assess large-scale brain circuit dynamics in behaving animals remain limited. Here we present compact, high-density arrays of optical fibers that can be chronically implanted into the mammalian brain, enabling multi-fiber photometry as well as optogenetic perturbations across many regions. In mice engaged in a texture discrimination task we achieved simultaneous photometric calcium recordings from networks of 12 to 48 brain regions, including striatal, thalamic, hippocampal, and cortical areas. Furthermore, we optically perturbed specific subsets of regions in VGAT-ChR2 mice by using a spatial light modulator to address the respective fiber channels. Perturbation of ventral thalamic nuclei caused distributed network modulation and behavioral deficits. Finally, we demonstrate multi-fiber photometry in freely moving animals, including simultaneous recordings from two mice during social interaction. Thus, high-density multi-fiber arrays are simple, low-cost, and versatile tools that open novel ways to investigate large-scale brain dynamics during behavior.