Context and space coding in mossy cell population activity.

The dentate gyrus plays a key role in the discrimination of memories by segregating and storing similar episodes. Whether hilar mossy cells, which constitute a major excitatory principal cell type in the mammalian hippocampus, contribute to this decorrelation function has remained largely unclear. Using two-photon calcium imaging of head-fixed mice performing a spatial virtual reality task, we show that mossy cell populations robustly discriminate between familiar and novel environments. The degree of discrimination depends on the extent of visual cue differences between contexts. A context decoder revealed that successful environmental classification is explained mainly by activity difference scores of mossy cells. By decoding mouse position, we reveal that in addition to place cells, the coordinated activity among active mossy cells markedly contributes to the encoding of space. Thus, by decorrelating context information according to the degree of environmental differences, mossy cell populations support pattern separation processes within the dentate gyrus.

A persistent prefrontal reference frame across time and task rules.

Behavior can be remarkably consistent, even over extended time periods, yet whether this is reflected in stable or 'drifting' neuronal responses to task features remains controversial. Here, we find a persistently active ensemble of neurons in the medial prefrontal cortex (mPFC) of mice that reliably maintains trajectory-specific tuning over several weeks while performing an olfaction-guided spatial memory task. This task-specific reference frame is stabilized during learning, upon which repeatedly active neurons show little representational drift and maintain their trajectory-specific tuning across long pauses in task exposure and across repeated changes in cue-target location pairings. These data thus suggest a 'core ensemble' of prefrontal neurons forming a reference frame of task-relevant space for the performance of consistent behavior over extended periods of time.

Neuronal tuning to threat exposure remains stable in the mouse prefrontal cortex over multiple days.

Intense threat elicits action in the form of active and passive coping. The medial prefrontal cortex (mPFC) executes top-level control over the selection of threat coping strategies, but the dynamics of mPFC activity upon continuing threat encounters remain unexplored. Here, we used 1-photon calcium imaging in mice to probe the activity of prefrontal pyramidal cells during repeated exposure to intense threat in a tail suspension (TS) paradigm. A subset of prefrontal neurons displayed selective activation during TS, which was stably maintained over days. During threat, neurons showed specific tuning to active or passive coping. These responses were unrelated to general motion tuning and persisted over days. Moreover, the neural manifold traversed by low-dimensional population activity remained stable over subsequent days of TS exposure and was preserved across individuals. These data thus reveal a specific, temporally, and interindividually conserved repertoire of prefrontal tuning to behavioral responses under threat.

Determination of n-Type Doping Level in Single GaAs Nanowires by Cathodoluminescence.

We present an effective method of determining the doping level in n-type III-V semiconductors at the nanoscale. Low-temperature and room-temperature cathodoluminescence (CL) measurements are carried out on single Si-doped GaAs nanowires. The spectral shift to higher energy (Burstein-Moss shift) and the broadening of luminescence spectra are signatures of increased electron densities. They are compared to the CL spectra of calibrated Si-doped GaAs layers, whose doping levels are determined by Hall measurements. We apply the generalized Planck's law to fit the whole spectra, taking into account the electron occupation in the conduction band, the bandgap narrowing, and band tails. The electron Fermi levels are used to determine the free electron concentrations, and we infer nanowire doping of 6 × 1017 to 1 × 1018 cm-3. These results show that cathodoluminescence provides a robust way to probe carrier concentrations in semiconductors with the possibility of mapping spatial inhomogeneities at the nanoscale.

Influenza A virus upregulates PRPF8 gene expression to increase virus production.

A ddRT-PCR analysis was performed to detect cellular genes that are differentially expressed after influenza A virus (H1N1) infection of A549 cells. After ddRT-PCR, eight DNA fragments were identified. PRPF8, one of the cellular genes that were upregulated after virus infection, was further analyzed since it has previously been identified as a cellular factor required for influenza virus replication. The upregulation of PRPF8 gene expression after viral infection was confirmed using real-time RT-PCR for mRNA detection and Western blot analysis for protein detection. Influenza A virus also upregulated the PRPF8 promoter in a reporter assay. In addition to H1N1, influenza A virus H3N2 and influenza B virus could also activate PRPF8 expression. Therefore, upregulation of PRPF8 expression might be important for the replication of different influenza viruses. Indeed, overexpression of PRPF8 gene enhanced virus production, while knockdown of expression of this gene reduced viral production significantly. To determine which viral protein could enhance PRPF8 gene expression, individual viral genes were cloned and expressed. Among the different viral proteins, expression of either the viral NS1 or PB1 gene could upregulate the PRPF8 expression. Our results from this study indicate that influenza A virus upregulates cellular PRPF8 gene expression through viral NS1 and PB1 proteins to increase virus production.

Both core and F proteins of hepatitis C virus could enhance cell proliferation in transgenic mice.

The role of the protein encoded by the alternative open reading frame (ARF/F/core+1) of the Hepatitis C virus (HCV) genome in viral pathogenesis remains unknown. The different forms of ARF/F/core+1 protein were labile in cultured cells, a myc-tag fused at the N-terminus of the F protein made it more stable. To determine the role of core and F proteins in HCV pathogenesis, transgenic mice with either protein expression under the control of Albumin promoter were generated. Expression of core protein and F protein with myc tag (myc-F) could be detected by Western blotting analysis in the livers of these mice. The ratio of liver to body weight is increased for both core and myc-F transgenic mice compared to that of wild type mice. Indeed, the proliferating cell nuclear antigen protein, a proliferation marker, was up-regulated in the transgenic mice with core or myc-F protein. Further analyses by microarray and Western blotting suggested that ß-catenin signaling pathway was activated by either core or myc-F protein in the transgenic mice. These transgenic mice were further treated with either Diethynitrosamine (a tumor initiator) or Phenobarbital (a tumor promoter). Phenobarbital but not Diethynitrosamine treatment could increase the liver/body weight ratio of these mice. However, no tumor formation was observed in these mice. In conclusion, HCV core and myc-F proteins could induce hepatocyte proliferation in the transgenic mice possibly through ß-catenin signaling pathway.