Recent evidence suggests that mesoscopic neural oscillations measured via intracranial electroencephalography exhibit spatial representations, which were previously only observed at the micro-and macroscopic level of brain organization. Specifically, theta (and gamma) oscillations correlate with movement, speed, distance, specific locations, and goal proximity to boundaries. In entorhinal cortex, they exhibit hexadirectional modulation, which is putatively linked to grid cell activity. Understanding this mesoscopic neural code is crucial because information represented by oscillatory power and phase may complement the information content at other levels of brain organization. Mesoscopic neural oscillations help bridge the gap between single-neuron and macroscopic brain signals of spatial navigation and may provide a mechanistic basis for novel biomarkers and therapeutic targets to treat diseases causing spatial disorientation.

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Autophagy is a major degradation system which processes substrates through the steps of autophagosome formation, autophagosome-lysosome fusion, and substrate degradation. Aberrant autophagic fl ux is present in many pathological conditions including neurodegeneration and tumors. CHIP/STUB1, an E3 ligase, plays an important role in neurodegeneration. In this study, we identifi ed the regulation of autophagic flux by CHIP (carboxy-terminus of Hsc70-interacting protein). Knockdown of CHIP induced autophagosome formation through increasing the PTEN protein level and decreasing the AKT/mTOR activity as well as decreasing phosphorylation of ULK1 on Ser757. However, degradation of the autophagic substrate p62 was disturbed by knockdown of CHIP, suggesting an abnormality of autophagic flux. Furthermore, knockdown of CHIP increased the susceptibility of cells to autophagic cell death induced by bafi lomycin A1. Thus, our data suggest that CHIP plays roles in the regulation of autophagic fl ux.

Objectives: Inwardly rectifying potassium current plays critical roles in setting resting membrane potential and thus modulating the excitability of many excitable cells including the hair cells in inner ears, which are excitable during early development. Up to 7 subfamilies have been identified as channels for this current. The present study investigated the developmental and spatial expression of one member, Kir2.1, in the sensorineural epithelia and spiral ganglion neurons of mouse cochleae starting from neonatal stage to the maturation of hearing function, in an attempt to verify its role in the postnatal cochlear development. Methods: The distribution of Kir2.1 protein and mRNA was observed using immunofluorescence staining and in situ hybridization on samples of surface preparation and cross sections of cochleae. The protein and mRNA were further measured with semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting to show the developmental change of this channel in the cochlea of mice. Results: The expression of Kir2.1 appears to have a clear temporal pattern: increasing from the first postnatal day (PD0) to PD12 and then quickly decreasing after that. The expression cannot be detected on PD20. Throughout this developmental pattern, the expression was stronger at the basal turn on PD0 and shifted upwards (longitudinal gradient), so that stronger signals were generally seen in the apical parts of the cochlea after PD0. A radial gradient of the Kir2.1 protein was also evident with a stronger and consistent signal usually occurring on row 3 outer hair cells. The spatial and developmental changes of Kir2.1 mRNA in in situ hybridization exhibited similar patterns as seen for the Kir2.1 protein on PD8 and PD12. Western blot data showed a slightly higher concentration of the protein in the apical half of the cochlea and a slight increase from PD4 to PD12. This result is consistent with the quantification of mRNA in RT-PCR. No significant expression of Kir2.1 was found in spiral ganglion neurons. Conclusions: Kir2.1 exhibits a clear and temporal expression in the hair cells of mouse cochleae which may be related to the functional maturation of the hair cells and the neurons.

These data suggest that synaptic degeneration may be an initial molecular mechanism for neurodegeneration in glaucoma and appropriate NgR1 antagonism may delay the progression of the disease.