Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance

SummaryAn increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity.Video Abstrac

Neural field dynamics for growing brains

We propose an extended framework of two dimensional neural field with network between distant cortical areas as a model of global brain dynamics, and the models whose geometry of the neural field changes depending on the field dynamics as a model for growing brains. As a characteristic pattern with non-local and network interactions in neural field, pulser and memory are constructed. Possible applications to quantitative measurements of cortical activities of mouse and human brain development are briefly discussed

State-Dependent Modulation of Slow Wave Motifs towards Awakening

Slow cortical waves that propagate across the cerebral cortex forming large-scale spatiotemporal propagation patterns are a hallmark of non-REM sleep and anesthesia, but also occur during resting wakefulness. To investigate how the spatial temporal properties of slow waves change with the depth of anesthetic, we optically imaged population voltage transients generated by mouse layer 2/3 pyramidal neurons across one or two cortical hemispheres dorsally with a genetically encoded voltage indicator (GEVI). From deep barbiturate anesthesia to light barbiturate sedation, depolarizing wave events recruiting at least 50% of the imaged cortical area consistently appeared as a conserved repertoire of distinct wave motifs. Toward awakening, the incidence of individual motifs changed systematically (the motif propagating from visual to motor areas increased while that from somatosensory to visual areas decreased) and both local and global cortical dynamics accelerated. These findings highlight that functional endogenous interactions between distant cortical areas are not only constrained by anatomical connectivity, but can also be modulated by the brain state

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Data from: The impact of bilateral ongoing activity on evoked responses in mouse cortex

In the absence of external stimuli or overt behavior, the activity of the left and right cortical hemispheres shows fluctuations that are largely bilateral. Here we show that these fluctuations are largely responsible for the variability observed in cortical responses to sensory stimuli. Using widefield imaging of voltage and calcium signals, we measured activity in the cortex of mice performing a visual detection task. Bilateral fluctuations invested all areas, particularly those closest to the midline. Activity was less bilateral in the monocular region of primary visual cortex and, especially during task engagement, in secondary motor cortex. Ongoing bilateral fluctuations dominated unilateral visual responses, and interacted additively with them, explaining much of the variance in trial-by-trial activity. Even though these fluctuations occurred in regions necessary for the task, they did not affect detection behavior. We conclude that bilateral ongoing activity continues during visual stimulation and has a powerful additive impact on visual responses