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.
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.
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