Astrocyte deletion of α2-Na/K ATPase triggers episodic motor paralysis in mice via a metabolic pathway.

Familial hemiplegic migraine is an episodic neurological disorder characterized by transient sensory and motor symptoms and signs. Mutations of the ion pump α2-Na/K ATPase cause familial hemiplegic migraine, but the mechanisms by which α2-Na/K ATPase mutations lead to the migraine phenotype remain incompletely understood. Here, we show that mice in which α2-Na/K ATPase is conditionally deleted in astrocytes display episodic paralysis. Functional neuroimaging reveals that conditional α2-Na/K ATPase knockout triggers spontaneous cortical spreading depression events that are associated with EEG low voltage activity events, which correlate with transient motor impairment in these mice. Transcriptomic and metabolomic analyses show that α2-Na/K ATPase loss alters metabolic gene expression with consequent serine and glycine elevation in the brain. A serine- and glycine-free diet rescues the transient motor impairment in conditional α2-Na/K ATPase knockout mice. Together, our findings define a metabolic mechanism regulated by astrocytic α2-Na/K ATPase that triggers episodic motor paralysis in mice.

Designing a large field-of-view two-photon microscope using optical invariant analysis.

Conventional two-photon microscopy (TPM) is capable of imaging neural dynamics with subcellular resolution, but it is limited to a field-of-view (FOV) diameter [Formula: see text]. Although there has been recent progress in extending the FOV in TPM, a principled design approach for developing large FOV TPM (LF-TPM) with off-the-shelf components has yet to be established. Therefore, we present a design strategy that depends on analyzing the optical invariant of commercially available objectives, relay lenses, mirror scanners, and emission collection systems in isolation. Components are then selected to maximize the space-bandwidth product of the integrated microscope. In comparison with other LF-TPM systems, our strategy simplifies the sequence of design decisions and is applicable to extending the FOV in any microscope with an optical relay. The microscope we constructed with this design approach can image [Formula: see text] lateral and [Formula: see text] axial resolution over a 7-mm diameter FOV, which is a 100-fold increase in FOV compared with conventional TPM. As a demonstration of the potential that LF-TPM has on understanding the microarchitecture of the mouse brain across interhemispheric regions, we performed in vivo imaging of both the cerebral vasculature and microglia cell bodies over the mouse cortex.

Lightweight sCMOS-based high-density diffuse optical tomography.

Though optical imaging of human brain function is gaining momentum, widespread adoption is restricted in part by a tradeoff among cap wearability, field of view, and resolution. To increase coverage while maintaining functional magnetic resonance imaging (fMRI)-comparable image quality, optical systems require more fibers. However, these modifications drastically reduce the wearability of the imaging cap. The primary obstacle to optimizing wearability is cap weight, which is largely determined by fiber diameter. Smaller fibers collect less light and lead to challenges in obtaining adequate signal-to-noise ratio. Here, we report on a design that leverages the exquisite sensitivity of scientific CMOS cameras to use fibers with ∼30× smaller cross-sectional area than current high-density diffuse optical tomography (HD-DOT) systems. This superpixel sCMOS DOT (SP-DOT) system uses 200-µm -diameter fibers that facilitate a lightweight, wearable cap. We developed a superpixel algorithm with pixel binning and electronic noise subtraction to provide high dynamic range ( >105 ), high frame rate ( >6 Hz ), and a low effective detectivity threshold ( ∼200 fW/Hz1/2-mm2 ), each comparable with previous HD-DOT systems. To assess system performance, we present retinotopic mapping of the visual cortex ( n=5 subjects). SP-DOT offers a practical solution to providing a wearable, large field-of-view, and high-resolution optical neuroimaging system.

Cerebral functional connectivity and Mayer waves in mice: Phenomena and separability.

Resting-state functional connectivity is a growing neuroimaging approach that analyses the spatiotemporal structure of spontaneous brain activity, often using low-frequency (<0.08 Hz) hemodynamics. In addition to these fluctuations, there are two other low-frequency hemodynamic oscillations in a nearby spectral region (0.1-0.4 Hz) that have been reported in the brain: vasomotion and Mayer waves. Despite how close in frequency these phenomena exist, there is little research on how vasomotion and Mayer waves are related to or affect resting-state functional connectivity. In this study, we analyze spontaneous hemodynamic fluctuations over the mouse cortex using optical intrinsic signal imaging. We found spontaneous occurrence of oscillatory hemodynamics ∼0.2 Hz consistent with the properties of Mayer waves reported in the literature. Across a group of mice (n = 19), there was a large variability in the magnitude of Mayer waves. However, regardless of the magnitude of Mayer waves, functional connectivity patterns could be recovered from hemodynamic signals when filtered to the lower frequency band, 0.01-0.08 Hz. Our results demonstrate that both Mayer waves and resting-state functional connectivity patterns can co-exist simultaneously, and that they can be separated by applying bandpass filters.