Modulation of auditory responses by modality-specific attention in rat primary auditory cortex

How does attention modulate sensory representations? In order to probe the underlying neural mechanisms, we established a simple rodent model of modality-specific attention. Here we describe results of experiments in freely moving rats in which we have used tetrodes to record neural responses in primary auditory cortex (area A1) while subjects performed this behavior.

Subjects were first trained to perform distinct auditory and olfactory two alternative forced-choice (2AFC) tasks. Training and testing were conducted in a custom three-poke computer-controlled behavioral apparatus. Subjects initiated trials with a center-poke, which triggered presentation of a tone (either 5 or 15 Hz), an odor (either R(-)-2-Octanol or S(+)-2-Octanol), or both. Subjects responded moving to the left or right poke. Correct responses were rewarded with water. Auditory and olfactory blocks (of 50 trials each) were interleaved in a single session. In auditory blocks, pure tones were either presented with or without a null odor (caproic acid, n=2 and 3 respectively), and subjects were cued to perform the task based on auditory stimuli. In olfactory blocks, both odors and pure tones were presented simultaneously, and subjects were cued to perform the task based on olfactory stimuli.

After subjects reached consistent performance on the interleaved blocks, tetrode drives were implanted in primary auditory cortex of the left hemisphere. Single unit responses to tones were heterogeneous, and included transient, sustained, and suppressed. Among 304 responsive units recorded, 19% (58 units) showed modality-specific attentional modulation of at least one of the tone-evoked responses; in most cases, the responses to a particular auditory stimulus was enhanced in the auditory block (or, equivalently, suppressed in the olfactory block). In addition, we also observed modality-specific attentional modulation of the spontaneous activity in similar proportion of units (61 units). 

Our results suggest that shifting attention from audition to olfaction and back can modulate the activity of single neurons in primary auditory cortex

Neural Mechanisms of Selective Auditory Attention in Rats (Dissertation)

How does attention modulate sensory representations? In order to probe the underlying neural mechanisms, we established a simple rodent model of modality-specific attention. Rats were trained to perform distinct auditory two-tone discrimination and olfactory odor discrimination in a two alternative choice (2AC) paradigm. 
To determine auditory cortex’s role in this frequency discrimination task, we used GABA-A receptor agonist muscimol to transiently and reversibly inactivate auditory cortexes bilaterally in rats performing simple interleaved auditory and olfactory discrimination. With olfactory discrimination performance serving as internal control for motivation and decision making capability, we found only auditory two-tone discrimination was selectively impaired in these rats. This shows the auditory cortex is involved in this two-tone discrimination task.
To investigate the neural correlate of modality-specific attention in the auditory cortex, we trained rats to perform interleaved auditory and olfactory blocks (of 50~70 trials each) in a single session. In auditory blocks, pure tones were either presented with or without a neutral odor (caproic acid, n=2 and 3 respectively), and subjects were rewarded for discriminating auditory stimuli. In olfactory blocks, both task odors and pure tones were presented simultaneously, and subjects were rewarded for discriminating olfactory stimuli. We recorded neural responses in primary auditory cortex (area A1) in freely moving rats while subjects performed this behavior. Single unit responses to tones were heterogeneous, and included transient, sustained, and suppressed. We found 205 of 802 units recorded responsive to the stimuli we used. Of these 205 units, 18.5% showed modality-specific attentional modulation of the anticipatory activity before tone onset. In addition, we also observed in smaller proportion of units (11.2%) modality-specific attentional modulation of the tone-evoked responses; in most cases, the responses to a particular auditory stimulus was enhanced in the auditory block (or, equivalently, suppressed in the olfactory block). Attention increased choice probability of the population in the auditory block. We have also observed significant behavior choice probability in small proportions of units. 
Our results suggest that shifting attention between audition to olfaction tasks can modulate the activity of single neurons in primary auditory cortex

Rule learning enhances structural plasticity of long-range axons in frontal cortex.

Rules encompass cue-action-outcome associations used to guide decisions and strategies in a specific context. Subregions of the frontal cortex including the orbitofrontal cortex (OFC) and dorsomedial prefrontal cortex (dmPFC) are implicated in rule learning, although changes in structural connectivity underlying rule learning are poorly understood. We imaged OFC axonal projections to dmPFC during training in a multiple choice foraging task and used a reinforcement learning model to quantify explore-exploit strategy use and prediction error magnitude. Here we show that rule training, but not experience of reward alone, enhances OFC bouton plasticity. Baseline bouton density and gains during training correlate with rule exploitation, while bouton loss correlates with exploration and scales with the magnitude of experienced prediction errors. We conclude that rule learning sculpts frontal cortex interconnectivity and adjusts a thermostat for the explore-exploit balance

The role of cytochrome c oxidase subunit Va in non-small cell lung carcinoma cells: association with migration, invasion and prediction of distant metastasis

BACKGROUND: Lung cancer is one of the most lethal malignancies worldwide, but useful biomarkers of lung cancer are still insufficient. The aim of this study is to identify some membrane-bound protein(s) associated with migration and invasion in human non-small cell lung cancer (NSCLC) cells. METHODS: We classified four NSCLC cell lines into high and low migration/invasion groups by Transwell and Matrigel assays. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), we identified 10 membrane-associated proteins being significantly overexpressed in the high migration/invasion group. The expression of the target protein in the four NSCLC cell lines was then confirmed by reverse transcription polymerase chain reaction (RT-PCR), western blot and immunostaining. RNA interference technique was applied to observe the influence of the target protein on migration and invasion. Gelatin zymography was also performed to evaluate the activities of matrix metalloproteinase (MMP)-2 and MMP-9. Expression condition of the target protein on surgical specimens was further examined by immunohistochemical staining and the clinicopathologic data were analyzed. RESULTS: We identified a mitochondria-bound protein cytochrome c oxidase subunit Va (COX Va) because of its abundant presence found exclusively in tumorous areas. We also demonstrated that migration and invasion of NSCLC cells decreased substantially after knocking down COX Va by siRNA. Meanwhile, we found a positive correlation between COX Va expression, Bcl-2 expression and activities of MMP-2 and MMP-9 in NSCLC cells. Immunohistochemical staining of surgically resected lung adenocarcinomas in 250 consecutive patients revealed that strong COX Va expression was found in 54.8% (137/250) of patients and correlated positively with the status of lymph node metastasis (P = 0.032). Furthermore, strong COX Va expression was associated with the presence of distant metastasis (P = 0.033). CONCLUSIONS: Our current study showed that COX Va may play a role in migration and invasion of NSCLC cells and can be used as a biomarker to predict aggressiveness of NSCLC

Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function

EBNA1 is the only Epstein–Barr virus (EBV) latent protein responsible for viral genome maintenance and is expressed in all EBV-infected cells. Zn2+ is essential for oligomerization of the functional EBNA1. We constructed an EBNA1 binding peptide with a Zn2+ chelator to create an EBNA1-specific inhibitor (ZRL5P4). ZRL5P4 by itself is sufficient to reactivate EBV from its latent infection. ZRL5P4 is able to emit unique responsive fluorescent signals once it binds with EBNA1 and a Zn2+ ion. ZRL5P4 can selectively disrupt the EBNA1 oligomerization and cause nasopharyngeal carcinoma (NPC) tumor shrinkage, possibly due to EBV lytic induction. Dicer1 seems essential for this lytic reactivation. As can been seen, EBNA1 is likely to maintain NPC cell survival by suppressing viral reactivation

Biomechanical comparison of a new stand-alone anterior lumbar interbody fusion cage with established fixation techniques – a three-dimensional finite element analysis

<p>Abstract</p> <p>Background</p> <p>Initial promise of a stand-alone interbody fusion cage to treat chronic back pain and restore disc height has not been realized. In some instances, a posterior spinal fixation has been used to enhance stability and increase fusion rate. In this manuscript, a new stand-alone cage is compared with conventional fixation methods based on the finite element analysis, with a focus on investigating cage-bone interface mechanics and stress distribution on the adjacent tissues.</p> <p>Methods</p> <p>Three trapezoid 8° interbody fusion cage models (dual paralleled cages, a single large cage, or a two-part cage consisting of a trapezoid box and threaded cylinder) were created with or without pedicle screws fixation to investigate the relative importance of the screws on the spinal segmental response. The contact stress on the facet joint, slip displacement of the cage on the endplate, and rotational angle of the upper vertebra were measured under different loading conditions.</p> <p>Results</p> <p>Simulation results demonstrated less facet stress and slip displacement with the maximal contact on the cage-bone interface. A stand-alone two-part cage had good slip behavior under compression, flexion, extension, lateral bending and torsion, as compared with the other two interbody cages, even with the additional posterior fixation. However, the two-part cage had the lowest rotational angles under flexion and torsion, but had no differences under extension and lateral bending.</p> <p>Conclusion</p> <p>The biomechanical benefit of a stand-alone two-part fusion cage can be justified. This device provided the stability required for interbody fusion, which supports clinical trials of the cage as an alternative to circumferential fixations.</p