Tau P301S Transgenic Mice Develop Gait and Eye Movement Impairments That Mimic Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with an estimated prevalence of 5-7 people in 100,000. Clinically characterized by impairments in gait, balance, and eye movements, as well as aggregated Tau pathology, PSP leads to death in approximately 5-8 years. No disease-modifying treatments are currently available. The contribution of Tau pathology to the symptoms of patients with PSP is poorly understood, in part due to lack of a rodent model that recapitulates characteristic aspects of PSP. Here, we assessed the hTau.P301S mouse for key clinical features of PSP, finding progressive impairments in balance and gait coordination. Additionally, we found impairments in fast vertical eye movements, one of the most distinctive features of PSP. Across animals, we found that Tau pathology in motor control regions correlated with motor deficits. These findings highlight the utility of the hP301S mouse in modeling key aspects of PSP.

Reactivity of Ultrathin Kagome Metal FeSn toward Oxygen and Water.

The kagome metal FeSn consists of alternating layers of kagome-lattice Fe3Sn and honeycomb Sn2 and exhibits great potential for applications in future low-energy electronics and spintronics because of an ideal combination of topological phases and high-temperature magnetic ordering. Robust synthesis methods for ultrathin FeSn films, as well as an understanding of their air stability, are crucial for its development and long-term operation in future devices. In this work, we realize large-area, <10 nm thick, epitaxial FeSn thin films and explore the oxidation process via synchrotron-based photoelectron spectroscopy using in situ oxygen and water dosing, as well as ex situ air exposure. Upon exposure to the atmosphere, the FeSn films are shown to be highly reactive, with a stable ∼3 nm thick oxide layer forming at the surface within 10 min. Notably, the surface Fe remains largely unoxidized when compared with Sn, which undergoes near-complete oxidation. Additionally, the band structure remains metallic under oxygen exposure. These are further confirmed with controlled in situ dosing of O2 and H2O, where only the Sn2 (stanene) interlayers within the FeSn lattice oxidize, suggesting the Fe3Sn kagome layers remain almost pristine. These results are in excellent agreement with first-principles calculations, which show that Fe-O bonds to the Fe3Sn layer are energetically unfavorable and a large formation energy preference of 1.37 eV for Sn-O bonds in the stanene Sn2 layer over Sn-O bonds in the kagome Fe3Sn layer. The demonstration that oxidation only occurs within the stanene layers and the preservation of the Dirac bands may provide additional avenues in how to engineer, handle, and prepare future kagome metal devices.

Cuprizone-induced oligodendrocyte loss and demyelination impairs recording performance of chronically implanted neural interfaces.

Biological inflammation induced during penetrating cortical injury can disrupt functional neuronal and glial activity within the cortex, resulting in potential recording failure of chronically implanted neural interfaces. Oligodendrocytes provide critical support for neuronal health and function through direct contact with neuronal soma and axons within the cortex. Given their fundamental role to regulate neuronal activity via myelin, coupled with their heightened vulnerability to metabolic brain injury due to high energetic demands, oligodendrocytes are hypothesized as a possible source of biological failure in declining recording performances of intracortical microelectrode devices. To determine the extent of their contribution to neuronal activity and function, a cuprizone-inducible model of oligodendrocyte depletion and demyelination in mice was performed prior to microelectrode implantation. At 5 weeks of cuprizone exposure, mice demonstrated significantly reduced cortical oligodendrocyte density and myelin expression. Mice were then implanted with functional recording microelectrodes in the visual cortex and neuronal activity was evaluated up to 7 weeks alongside continued cuprizone administration. Cuprizone-induced oligodendrocyte loss and demyelination was associated with significantly reduced recording performances at the onset of implantation, which remained relatively stable over time. In contast, recording performances for mice on a normal diet were intially elevated before decreasing over time to the recording level of tcuprizone-treated mice. Further electrophysiological analysis revealed deficits in multi-unit firing rates, frequency-dependent disruptions in neuronal oscillations, and altered laminar communication within the cortex of cuprizone-treated mice. Post-mortem immunohistochemistry revealed robust depletion of oligodendrocytes around implanted microelectrode arrays alongside comparable neuronal densities to control mice, suggesting that oligodendrocyte loss was a possible contributor to chronically impaired device performances. This study highlights potentially significant contributions from the oligodendrocyte lineage population concerning the biological integration and long-term functional performance of neural interfacing technology.