bioRxiv Science⌕ Search

Biology subjects

Zhang, Y.-X.

Publications and source records attributed to Zhang, Y.-X..

4 recordsLinked to original sources

PRRT2 as an auxiliary regulator of Nav channel slow inactivation

During sustained activity, voltage-gated sodium (Nav) channels enter a slow-inactivated state to limit cellular hyperexcitability. Disruption of this regulatory process has been implicated in skeletal, cardiac and neurological disorders. While the kinetics of this process are well characterized, its endogenous modulators remain unclear. Here, we identify Proline-Rich Transmembrane Protein 2 (PRRT2) as a native regulator of Nav channel slow inactivation. We show that PRRT2 facilitates the entry of Nav channels into the slow-inactivated state and delays their recovery, a regulatory effect conserved from zebrafish to humans. PRRT2 forms molecular complexes with Nav channels both in vitro and in vivo. In the mouse cortex, PRRT2 deficiency impairs the slow inactivation of Nav channels in neuronal axons, leading to reduced cortical resilience in response to hyperexcitable challenges. Together, these findings establish PRRT2 as a physiological modulator of Nav channel slow inactivation and reveal a mechanism that supports cortical resilience to pathological perturbations.

neuroscience↗

Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children with prelingual deafness provide a unique opportunity to study this developmental stage. Using functional near-infrared spectroscopy, we revealed that the brain of CI children was nearly irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. In addition, speech responses increased linearly in left sylvian parieto-temporal area and right inferior frontal gyrus, and noise responses changed in U shape in right supramarginal gyrus. Such cortical development predicted behavioral improvement. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition in the human brain. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/483211v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@d84974org.highwire.dtl.DTLVardef@1be9ba0org.highwire.dtl.DTLVardef@db5fb7org.highwire.dtl.DTLVardef@68f420_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe brain of cochlear implanted toddlers is functionally inferior to neonates C_LIO_LIHearing experiences drive functional development in auditory related cortical areas C_LIO_LISpeech and noise processing develop in anti-phasic oscillatory trajectories C_LIO_LIAuditory cortical development predicts post-implantation behavioral improvement C_LI

neuroscience↗

Dopamine enhanced auditory perceptual learning in humans via long-term memory consolidation

Dopamine is known to modulate sensory plasticity in animal brain, but how it impacts perceptual learning in humans remains largely unknown. In a placebo-controlled, double-blinded training experiment with young healthy adults (both male and female), oral administration of Madopar, a dopamine precursor, during each of multiple training sessions was shown to enhance auditory perceptual learning, particularly in late training sessions. Madopar also enhanced learning and transfer to working memory when tested outside the time widow of drug effect, which appeared to retain for at least 20 days. To test whether such learning modulation was mediated by the dopaminergic working memory network, the same dopamine manipulation was applied to working memory training, but to little influence on learning or transfer. Further, a neural network model of auditory perceptual learning revealed distinctive behavioural modulation patterns for proposed dopaminergic functions in the auditory cortex: trial-by-trial reinforcement signals (reward/reward prediction error and expected reward) and across-session memory consolidation. Only the memory consolidation simulations matched experimental observations. The results thus demonstrate that dopamine modulates human perceptual learning, mostly likely via enhancing memory consolidation over extended time scales.

neuroscience↗

Meta-microRNAs as potential noninvasive markers for early diagnosis of Alzheimer’s disease

IntroductionThe aim of this study was to investigate the potential role of a microRNA panel as early diagnostic markers for Alzheimers disease (AD).\n\nMethodsThe differentially expressed serum microRNAs were screened with microarray among cognitively normal controls (CNC), mild cognitive impairment (MCI), and AD. QRT-PCR assay was applied to evaluate differentially expressed microRNAs with two independent cohorts including 202 participants. Logistic regression model based on microRNA panel was constructed using a training cohort and then validated using an independent cohort.\n\nResultsFirst, four differentially expressed serum microRNAs (let-7g, miR-197, miR-126 and miR-29a) were found, which expressions were positively correlated with mini mental state examination (MMSE) score. Second, a microRNA panel with the four microRNAs demonstrated good diagnostic performance for MCI and AD with 84% and 92% accuracy. Third, when combined with MMSE score, the diagnostic performance of the microRNA panel was further improved.\n\nDiscussionBlood microRNAs are potential AD biomarkers that may lead to new diagnostic strategies.

neuroscience↗