Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior

• Published in: Neuron (Cambridge, Mass.) Vol. 112; no. 6; pp. 909 - 923.e9
• Main Authors: Vu, Mai-Anh T., Brown, Eleanor H., Wen, Michelle J., Noggle, Christian A., Zhang, Zicheng, Monk, Kevin J., Bouabid, Safa, Mroz, Lydia, Graham, Benjamin M., Zhuo, Yizhou, Li, Yulong, Otchy, Timothy M., Tian, Lin, Davison, Ian G., Boas, David A., Howe, Mark W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.03.2024
• Subjects: Animals; behaving mice; Brain - physiology; Corpus Striatum; Dopamine; freely moving mice; Mice; micro-CT scanning; multi-fiber photometry; Neostriatum; neuromodulator dynamics; Optogenetics - methods; striatum; targeted optogenetics; freely moving mice; multi-fiber photometry; targeted optogenetics; striatum; neuromodulator dynamics; dopamine; behaving mice; micro-CT scanning
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2023.12.011

Neural population dynamics relevant to behavior vary over multiple spatial and temporal scales across three-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice, enabling the investigation of cell-type- and neurotransmitter-specific signals over arbitrary 3D volumes at a spatial resolution and coverage previously inaccessible. We applied this method to resolve rapid dopamine release dynamics across the striatum, revealing distinct, modality-specific spatiotemporal patterns in response to salient sensory stimuli extending over millimeters of tissue. Targeted optogenetics enabled flexible control of neural signaling on multiple spatial scales, better matching endogenous signaling patterns, and the spatial localization of behavioral function across large circuits. •A new customizable, targeted, and dense micro-fiber array approach for behaving mice•Measurements and manipulations of distributed neural dynamics over large 3D volumes•Modality-specific patterns of striatum-wide dopamine release in response to salient stimuli•Spatial mapping of a behavioral function via serially targeted striatum stimulations Vu et al. present a customizable approach using small-diameter optical fibers that enables dense measurements and targeted manipulations of distributed neural activity over large 3D volumes at a spatial resolution and coverage previously inaccessible. They reveal modality-specific spatiotemporal patterns of striatum-wide dopamine release in response to sensory stimuli and precise mapping of a specific behavior onto striatal location.