Summary At various stages of the visual system, visual responses are modulated by arousal. Here, we find that in mice this modulation operates as early as in the first synapse from the retina and even in retinal axons. To measure retinal activity in the awake, intact brain, we imaged the synaptic boutons of retinal axons in the superior colliculus. Their activity depended not only on vision but also on running speed and pupil size, regardless of retinal illumination. Arousal typically reduced their visual responses and selectivity for direction and orientation. Recordings from retinal axons in the optic tract revealed that arousal modulates the firing of some retinal ganglion cells. Arousal had similar effects postsynaptically in colliculus neurons, independent of activity in the other main source of visual inputs to the colliculus, the primary visual cortex. These results indicate that arousal modulates activity at every stage of the mouse visual system.

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Transgenic mouse lines are invaluable tools for neuroscience but as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically-encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, though rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

Neural recording devices normally require one output connection for each electrode. This constrains the number of electrodes that can be accommodated by the thin shafts of implantable probes. Sharing a single output connection between multiple electrodes relaxes this constraint and permits designs of ultra-high density neural probes.Here we report the design and in vivo validation of such a device, a complementary metal-oxidesemiconductor (CMOS) scanning probe with 1344 electrodes and 12 reference electrodes along an 8.1 mm x 100 μm x 50 μm shaft; the outcome of the European research project NeuroSeeker. This technology presented new challenges for data management and visualization, and we also report new methods addressing these challenges developed within NeuroSeeker.Scanning CMOS technology allows the fabrication of much smaller, denser electrode arrays. To help design electrode configurations for future probes, several recordings from many different brain regions were made with an ultra-dense passive probe fabricated using CMOS process. All datasets are available online.

Understanding whole-brain-scale electrophysiological recordings will rely on the collective work of multiple labs. Because two labs recording from the same brain area often reach different conclusions, it is critical to quantify and control for features that decrease reproducibility. To address these issues, we formed a multi-lab collaboration using a shared, open-source behavioral task and experimental apparatus. We repeatedly inserted Neuropixels multi-electrode probes targeting the same brain locations (including posterior parietal cortex, hippocampus, and thalamus) in mice performing the behavioral task. We gathered data across 9 labs and developed a common histological and data processing pipeline to analyze the resulting large datasets. After applying stringent behavioral, histological, and electrophysiological quality-control criteria, we found that neuronal yield, firing rates, spike amplitudes, and task-modulated neuronal activity were reproducible across laboratories. To quantify variance in neural activity explained by task variables (e.g., stimulus onset time), behavioral variables (timing of licks/paw movements), and other variables (e.g., spatial location in the brain or the lab ID), we developed a multi-task neural network encoding model that extends common, simpler regression approaches by allowing nonlinear interactions between variables. We found that within-lab random effects captured by this model were comparable to between-lab random effects. Taken together, these results demonstrate that across-lab standardization of electrophysiological procedures can lead to reproducible results across labs. Moreover, our protocols to achieve reproducibility, along with our analyses to evaluate it are openly accessible to the scientific community, along with our extensive electrophysiological dataset with corresponding behavior and open-source analysis code.

Top-down coordination of local cortical state during selective attention Highlights d Cortical excitability fluctuations are coordinated across visual areas d During selective attention, these fluctuations are driven in a top-down manner d The degree of coordination depends on shared spatial representation d Increased cortical state coordination predicts better behavioral performance

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Widefield calcium imaging has recently emerged as a powerful experimental technique to record coordinated large-scale brain activity. These measurements present a unique opportunity to characterize spatiotemporally coherent structures that underlie neural activity across many regions of the brain. In this work, we leverage analytic techniques from fluid dynamics to develop a visualization framework that highlights features of flow across the cortex, mapping wavefronts that may be correlated with behavioural events. First, we transform the time series of widefield calcium images into time-varying vector fields using optic flow. Next, we extract concise diagrams summarizing the dynamics, which we refer to as FLOW (flow lines in optical widefield imaging) portraits . These FLOW portraits provide an intuitive map of dynamic calcium activity, including regions of initiation and termination, as well as the direction and extent of activity spread. To extract these structures, we use the finite-time Lyapunov exponent technique developed to analyse time-varying manifolds in unsteady fluids. Importantly, our approach captures coherent structures that are poorly represented by traditional modal decomposition techniques. We demonstrate the application of FLOW portraits on three simple synthetic datasets and two widefield calcium imaging datasets, including cortical waves in the developing mouse and spontaneous cortical activity in an adult mouse.