Thyroid hormone controls the timely differentiation of oligodendrocytes (OLs), and its deficiency can delay myelin development and cause mental retardation. Previous studies showed that the active thyroid hormone T3 is converted from its prohormone T4 by the selenoprotein DIO2, whose mRNA is primarily expressed in astrocytes in the central nervous system. In the present study, we discovered that SECISBP2L is highly expressed in differentiating OLs and is required for DIO2 translation. Conditional knockout of Secisbp2l in OL lineage resulted in a decreased level of DIO2 and T3, accompanied by impaired OL differentiation, hypomyelination and motor deficits in both sexes of mice. Moreover, the defective differentiation of OLs in Secisbp2l mutants can be alleviated by T3 or its analog, but not the prohormone T4. The present study has provided strong evidence for the autonomous regulation of OL differentiation by its intrinsic T3 production mediated by the novel SECISBP2L-DIO2-T3 pathway during myelin developme...

Speech perception in noisy environments is enhanced by seeing facial movements of communication partners. However, the neural mechanisms by which audio and visual speech are combined are not fully understood. We explore MEG phase locking to auditory and visual signals in MEG recordings from 14 human participants (6 females, 8 males) that reported words from single spoken sentences. We manipulated the acoustic clarity and visual speech signals such that critical speech information is present in auditory, visual or both modalities. MEG coherence analysis revealed that both auditory and visual speech envelopes (auditory amplitude modulations and lip aperture changes) were phase-locked to 2-6Hz brain responses in auditory and visual cortex, consistent with entrainment to syllable-rate components. Partial coherence analysis was used to separate neural responses to correlated audio-visual signals and showed non-zero phase locking to auditory envelope in occipital cortex during audio-visual (AV) speech. Furthermo...

Cognitive decline is a debilitating aspect of aging and neurodegenerative diseases such as Alzheimer’s disease that is closely associated with mitochondrial dysfunction, increased reactive oxygen species (ROS), neuroinflammation and astrogliosis. This study investigated the effects of decreased mitochondrial antioxidant response specifically in astrocytes on cognitive performance and neuronal function in C57Bl/6J mice using a tamoxifen-inducible astrocyte-specific knockout of manganese superoxide dismutase (aSOD2-KO), a mitochondrial matrix antioxidant that detoxifies superoxide generated during mitochondrial respiration. We reduced astrocyte SOD2 levels in male and female mice at 11-12 months of age and tested in an automated home-cage (PhenoTyper) apparatus for diurnal patterns, spatial learning and memory function at 15 months of age. Astrocyte-specific SOD2-knockout impaired hippocampal-dependent spatial working memory and decreased cognitive flexibility in the reversal phase of the testing paradigm in...

Human society operates on large-scale cooperation. However, individual differences in cooperativeness and incentives to free-ride on others’ cooperation make large-scale cooperation fragile and can lead to reduced social-welfare. Thus, how individual cooperation spreads through human social networks remains puzzling from ecological, evolutionary and societal perspectives. Here, we identify oxytocin and costly punishment as biobehavioral mechanisms that facilitate the propagation of cooperation in social networks. In three laboratory experiments ( n = 870 human participants, 373 males and 497 females), individuals were embedded in heterogeneous networks and made repeated decisions with feedback in games of trust ( n = 342), ultimatum bargaining ( n = 324), and prisoner’s dilemma with punishment ( n = 204). In each heterogeneous network, individuals at central positions (hub nodes) were given intranasal oxytocin (or placebo). Giving oxytocin (versus matching placebo) to central individuals increased their tr...

The efferent pathway strengthens the auditory system for optimal performance by fine-tuning the response and protecting the inner ear from noise-induced damage. Although it has been well-documented that efference helps defend against hair cell and synaptic extinction, the mechanisms of its otoprotective role have still not been established. Specifically, the effect of efference on an individual hair cell’s recovery from mechanical overstimulation has not been demonstrated. In the current work, we explored the impact of efferent stimulation on this recovery using in vitro preparations of hair cells situated in the sacculi of American bullfrogs ( Rana catesbeiana ). In the absence of efferent stimulus, exposure of a hair bundle to high-amplitude mechanical deflection detuned it from its oscillatory regime, with the extent of detuning dependent on the applied signal. Efferent actuation concomitant with the hair bundle’s relaxation from a high-amplitude deflection notably changed the recovery profile and often...

When making a turn at a familiar intersection, we know what items and landmarks will come into view. These perceptual expectations, or predictions, come from our knowledge of the context, however it’s unclear how memory and perceptual systems interact to support the prediction and reactivation of sensory details in cortex. To address this, human participants learned the spatial layout of animals positioned in a cross maze. During fMRI, participants of both sexes navigated between animals to reach a target, and in the process saw a predictable sequence of five animal images. Critically, to isolate activity patterns related to item predictions, rather than bottom-up inputs, one quarter of trials ended early, with a blank screen presented instead. Using multivariate pattern similarity analysis, we reveal that activity patterns in early visual cortex, posterior medial regions, and the posterior hippocampus showed greater similarity when seeing the same item compared to different items. Further, item effects in...

Cochlear sensitivity, essential for communication and exploiting the acoustic environment, results from sensory-motor outer hair cells (OHCs) operating in a structural scaffold of supporting cells and extracellular cortilymph (CL) within the organ of Corti (OoC). Cochlear sensitivity control is hypothesized to involve interaction between the OHCs and OoC supporting cells (e.g., Deiters’ cells (DCs) and outer pillar cells (OPCs)), but this has never been established in vivo . Here, we conditionally expressed channelrhodopsins (ChR2) specifically in male and female mouse DCs and OPCs. illumination of the OoC activated the nonselective ChR2 cation conductance and depolarized DCs when measured in vivo and in isolated OoC. Measurements of sound-induced cochlear mechanical and electrical responses revealed OoC illumination suppressed the normal functions of OoC supporting cells transiently and reversibly. OoC illumination blocked normally occurring continuous minor adjustments of tone-evoked basilar membrane (BM...

The nervous system is under tight energy constraints and must represent information efficiently. This is particularly relevant in the dorsal part of the medial superior temporal area (MSTd) in primates where neurons encode complex motion patterns in order to support a variety of behaviors. A sparse decomposition model based on a dimensionality reduction principle known as Nonnegative Matrix Factorization (NMF) was previously shown to account for a wide range of monkey MSTd visual response properties. This model resulted in sparse, “parts-based” representations that could be regarded as basis flow fields, a linear superposition of which accurately reconstructed the input stimuli. This model provided evidence that the seemingly-complex response properties of MSTd may be a by-product of MSTd neurons performing dimensionality reduction on their input. However, an open question is how a neural circuit could carry out this function. In the current study, we propose a Spiking Neural Network (SNN) model of MSTd ba...

Increasing loss of structure and function of neurons and decline in cognitive function is commonly seen during the progression of neurologic diseases, although the causes and initial symptoms of individual diseases are distinct. This observation suggests a convergence of common degenerative features. In myotonic dystrophy type 1 (DM1), the expression of expanded CUG RNA induces neurotransmission dysfunction before axon and dendrite degeneration and reduced MBNL2 expression associated with aberrant alternative splicing. The role of loss of function of MBNL2 in the pathogenesis of neurodegeneration and the causal mechanism of neurodegeneration-reduced expression of MBNL2 remain elusive. Here, we show that increased MBNL2 expression is associated with neuronal maturation and required for neuronal morphogenesis and the fetal to adult developmental transition of RNA processing. Neurodegenerative conditions including NMDA receptor (NMDAR)-mediated excitotoxicity and dysregulated calcium homeostasis triggered nuc...