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Healthy brain function requires a delicate balance between neural activity and local vascular dynamics. Perturbations to this balance, such as vessel diameter changes or fluctuations in red blood cell velocity, are thought to underlie a number of neurodegenerative and neurovascular diseases, including migraine, stroke, and epilepsy. Here, for the first time, we demonstrate high fidelity simultaneous acquisition of vascular and neural circuit dynamics in freely-moving animals using our newly developed nVue dual color miniscope. Our system enables simultaneous imaging of blood flow and neural activity in both superficial and deep-brain structures in awake, behaving rodents. By multiplexing two LEDs at up to 100hz, the nVue enables direct, real-time visualization of both hemodynamics and calcium activity in two channels. Additionally, we have augmented the Inscopix Data Processing Software package to capture time-varying estimates of vessel diameter and red blood cell (RBC) velocity in specific vessels. Vessel diameter is estimated as the full-width half maximum of a Lorentzian function fit to vessel cross-section, while RBC velocity is calculated based on time-lagged correlations between seed-pixels within individual regions of interest and all immediately neighboring pixels. Distances between correlation peaks are then plotted against time. Manual annotation of blood flow data was performed to establish a ground truth against which to validate the algorithm. The nVue blood flow imaging application offers a powerful, turn-key, multisystem workflow for simultaneously interrogating hemodynamics and neural circuit function in freely behaving animals which will profoundly expand the neurovascular coupling toolkit not only for basic and translational research but also for the development of novel preclinical therapeutics. Commercial This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The detection of novel stimuli is critical to learn and survive in a dynamic environment. Though novel stimuli powerfully affect brain activity, their impact on specific cell types and circuits is not well understood. Disinhibition is one candidate mechanism for novelty-induced enhancements in activity. Here we characterize the impact of stimulus novelty on disinhibitory circuit components using longitudinal 2-photon calcium imaging of Vip, Sst, and excitatory populations in the mouse visual cortex. Mice learn a behavioral task with stimuli that become highly familiar, then are tested on both familiar and novel stimuli. Mice consistently perform the task with novel stimuli, yet responses to stimulus presentations and stimulus omissions are dramatically altered. Further, we find that novelty modifies coding of visual as well as behavioral and task information. At the population level, the direction of these changes is consistent with engagement of the Vip-Sst disinhibitory circuit. At the single cell level, we identify separate clusters of Vip, Sst, and excitatory cells with unique patterns of novelty-induced coding changes. This study and the accompanying open-access dataset reveals the impact of novelty on sensory and behavioral representations in visual cortical circuits and establishes novelty as a key driver of cellular functional diversity.

The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically