Neuronal membrane proteasomes regulate neuronal circuit activity in vivo and are required for learning-induced behavioral plasticity.

Protein degradation is critical for brain function through processes that remain incompletely understood. Here, we investigated the in vivo function of the 20S neuronal membrane proteasome (NMP) in the brain of Xenopus laevis tadpoles. With biochemistry, immunohistochemistry, and electron microscopy, we demonstrated that NMPs are conserved in the tadpole brain and preferentially degrade neuronal activity-induced newly synthesized proteins in vivo. Using in vivo calcium imaging in the optic tectum, we showed that acute NMP inhibition rapidly increased spontaneous neuronal activity, resulting in hypersynchronization across tectal neurons. At the circuit level, inhibiting NMPs abolished learning-dependent improvement in visuomotor behavior in live animals and caused a significant deterioration in basal behavioral performance following visual training with enhanced visual experience. Our data provide in vivo characterization of NMP functions in the vertebrate nervous system and suggest that NMP-mediated degradation of activity-induced nascent proteins may serve as a homeostatic modulatory mechanism in neurons that is critical for regulating neuronal activity and experience-dependent circuit plasticity.

Altered auditory feedback improves speech intelligibility in individuals diagnosed with Parkinson's disease - A pilot study.

INTRODUCTION: The purpose of the current study was to evaluate speech intelligibility and speech rate in individuals with Parkinson's disease using altered auditory feedback (AAF) in comparison to age-matched healthy controls. Based on prior research, it is hypothesized that the use of AAF will improve participants' speech intelligibility. METHOD: Five individuals with Parkinson's disease (clinical group) and five age-matched healthy controls aged 50 and above participated in this pre/post group experiment. All participants completed reading and monologue tasks with and without AAF. The AAF delayed the participants' auditory feedback by 150 milliseconds and altered it by 1/20 octave. Thirty-two naïve listeners listened to the recorded participants' speech samples (with and without AAF) randomly and rated the participants' speech intelligibility. RESULTS: Results of the mixed model ANOVA revealed that participants in the control group had significantly higher speech intelligibility scores than the participants in the clinical group. Post-hoc tests indicated that only participants in the clinical group were more intelligible with AAF than without AAF. Participants in the clinical group had better speech intelligibility when reading the passage than speaking the monologue. With regards to speech rate, participants spoke more slowly with AAF than without. Finally, there was a negative correlation between speech rate and speech intelligibility. CONCLUSION: The current findings support our hypothesis that AAF improves speech intelligibility in people with Parkinson's disease, though not healthy controls. Future research should evaluate the long-term effect of AAF use on speech intelligibility in people with Parkinson's disease.

Analytic consistency and neural correlates of peak alpha frequency in the study of pain.

BACKGROUND: Several studies have found evidence of reduced resting-state peak alpha frequency (PAF) in populations with pain. However, the stability of PAF from different analytic pipelines used to study pain has not been determined and underlying neural correlates of PAF have not been validated in humans. NEW METHOD: For the first time we compare analytic pipelines and the relationship of PAF to activity in the whole brain and thalamus, a hypothesized generator of PAF. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data and subsequently 64 channel resting-state electroencephalographic (EEG) from 47 healthy men, controls from an ongoing study of chronic prostatitis (a pain condition affecting men). We identified important variations in EEG processing for PAF from a review of 17 papers investigating the relationship between pain and PAF. We tested three progressively complex pre-processing pipelines and varied four postprocessing variables (epoch length, alpha band, calculation method, and region-of-interest [ROI]) that were inconsistent across the literature. RESULTS: We found a single principal component, well-represented by the average PAF across all electrodes (grand-average PAF), explained > 95% of the variance across participants. We also found the grand-average PAF was highly correlated among the pre-processing pipelines and primarily impacted by calculation method and ROI. Across methods, interindividual differences in PAF were correlated with rs-fMRI-estimated activity in the thalamus, insula, cingulate, and sensory cortices. CONCLUSIONS: These results suggest PAF is a relatively stable marker with respect to common pre and post-processing methods used in pain research and reflects interindividual differences in thalamic and salience network function.