Sequences of cortical activation states encode search strategies during spatial navigation

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Sequences of cortical activation states encode search strategies during spatial navigation

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Successful goal-directed navigation requires an integration of multiple streams of sensory environments, incorporating those representations into goal-related plans, and actuating those goal-related plans. How this multi-sensory information is processed across the cortex during navigation is not well understood. To investigate this, we recorded cortex-wide calcium dynamics in Thy1-GCamp6f mice (n = 11) using the mini-mScope (Rynes*, Surinach* et al 2021), a head-mounted miniaturized microscope capable of mesoscale calcium imaging of large swathes of the dorsal cortex, in mice solving the Barnes maze. The Barnes maze consists of a single escape hole in the presence of mildly aversive sensory stimuli. Mice learned to successfully navigate to the escape hole predominantly using a random search strategy in early trials, progressing to serial search and spatial search strategies in later tests. A holistic view of the activity across the cortex during a rapid, ethologically relevant spatial learning task revealed neural states indicative of distinct sets of brain-wide circuits being recruited during navigation behaviors. Using an unsupervised algorithm, we clustered cortical activity via k-means clustering into sets of “states” characterized by instantaneous patterns of spatially distributed activity across the FOV of the cortex. We found 5-10 states in each mouse and 7 states across mice. This low-dimensional space allowed the discovery of search strategy-specific spatiotemporal sequences of activity. Trial initiation was marked by repeated macro timescale patterns of state activation with a prolonged duration of activation of states involving high calcium activity in the frontal regions of the cortex occurring shortly after trial initiation. This frontal cortex-activated state coincided with mice approaching the edge of the maze from the center and occurred reliably in nonrandom search strategies. These events were preceded by sequences of state transitions that were distinct for serial and spatial search strategies.


University of Minnesota Ph.D. dissertation. May 2023. Major: Biomedical Engineering. Advisor: Suhasa Kodandaramaiah. 1 computer file (PDF); vi, 109 pages.

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Rynes, Mathew. (2023). Sequences of cortical activation states encode search strategies during spatial navigation. Retrieved from the University Digital Conservancy,

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