Gene Expression Omnibus database shows significantly downregulated expression of ubiquitin protein ligase E3 component N-recognin 1 (UBR1) in spinal cord injury (SCI). In this study, we investigated the mechanism of action of UBR1 in SCI. Following the establishment of SCI models in rats and PC12 cells, Basso–Beattie–Bresnahan (BBB) score and hematoxylin-eosin (H&E) and Nissl staining were used to evaluate SCI. The localization of NeuN/LC3 and the expression of LC3II/I, Beclin-1, and p62 were detected to assess autophagy. The expression of Bax, Bcl-2, and cleaved caspase-3 was detected and TdT-mediated dUTP-biotin nick end-labeling staining was employed to determine the changes in apoptosis. The N(6)-methyladenosine (m6A) modification level of UBR1 was analyzed by methylated RNA immunoprecipitation, and the binding of METTL14 and UBR1 mRNA was analyzed by photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation. UBR1 was poorly expressed, and METTL14 was highly expressed in rat and cel...

Opioid drugs are widely used as analgesics but cause respiratory depression, a potentially lethal side effect with overdose, by acting on μ-opioid receptors (MORs) expressed in brainstem regions involved in the control of breathing. Although many brainstem regions have been shown to regulate opioid-induced respiratory depression, the types of neurons involved have not been identified. Somatostatin is a major neuropeptide found in brainstem circuits regulating breathing, but it is unknown whether somatostatin-expressing circuits regulate respiratory depression by opioids. We examined the coexpression of Sst (gene encoding somatostatin) and Oprm1 (gene encoding MORs) mRNAs in brainstem regions involved in respiratory depression. Interestingly, Oprm1 mRNA expression was found in the majority (>50%) of Sst -expressing cells in the preBötzinger Complex, the nucleus tractus solitarius, the nucleus ambiguus, and the Kölliker–Fuse nucleus. We then compared respiratory responses to fentanyl between wild-type and Op...

Approximately 10% of births are preterm [PTB; <37 weeks gestational age (GA)], which confers risk for cognitive, behavioral, and mental health challenges. Using the large and relatively diverse (i.e., designed to reflect sociodemographic variation in the United States population) Adolescent Brain Cognitive Development Study (ABCD Study), we characterized the impact of PTB on brain structure in middle-late childhood (9–10 years). The ABCD sample covers the GA spectrum, and the large sample size (∼11,500) permits consideration of how associations between PTB and brain structure are impacted by GA, sex, birthweight, and analytic choices such as controlling for total brain size. We found a pattern of relative cortical thinning in temporoparietal and dorsal prefrontal regions and thickening of medial prefrontal and occipital regions in PTB compared with children born full term (≥37 weeks GA). This pattern was apparent when controlling for mean thickness and when considering moderate (>32 and <37 weeks GA) and v...

Animals are capable of representing different scale spaces from smaller to larger ones. However, most laboratory animals live their life in a narrow range of scale spaces like homecages and experimental setups, making it hard to extrapolate the spatial representation and learning process in large scale spaces from those in conventional scale spaces. Here, we developed a 3-m diameter Barnes maze (BM3), then explored whether spatial learning in the Barnes maze (BM) is calibrated by scale spaces. Spatial learning in the BM3 was successfully established with a lower learning rate than that in a conventional 1-m diameter Barnes maze (BM1). Specifically, analysis of exploration strategies revealed that the mice in the BM3 persistently searched certain places throughout the learning, while such places were rapidly decreased in the BM1. These results suggest dedicated exploration strategies requiring more trial-and-errors and computational resources in the BM3 than in the BM1, leading to a divergence of spatial le...

The cochlea hair cells transform mechanic sounds to neural signals with a remarkable sensitivity and resolution. This is achieved via the precisely sculpted mechanotransduction apparatus of the hair cells and the supporting structure of the cochlea. The shaping of the mechanotransduction apparatus, the staircased stereocilia bundles on the apical surface of the hair cells, requires an intricate regulatory network including planar cell polarity (PCP) and primary cilia genes in orienting stereocilia bundles and building molecular machinery of the apical protrusions. The mechanism linking these regulatory components is unknown. Here, we show that a small GTPase known for its role in protein trafficking, Rab11a, is required for ciliogenesis in hair cells during development in mice. In addition, in the absence of Rab11a, stereocilia bundles lost their cohesion and integrity, and mice are deaf. These data indicate an essential role of protein trafficking in the formation of hair cell mechanotransduction apparatu...

Experiments that take advantage of head-fixed behavioral tasks have been a staple of systems neuroscience research for half a century. More recently, rodents came to the forefront of these efforts, primarily because of the rich experimental possibilities afforded by modern genetic tools. There is, however, a considerable barrier to entering this field, requiring expertise in engineering, hardware and software development, and significant time and financial commitment. Here, we present a comprehensive, open-source hardware and software solution to implement a head-fixed environment for rodent behaviors (HERBs). Our solution provides access to three frequently used experimental frameworks (two-alternative forced choice, Go-NoGo, or passive sensory stimulus presentation) in a single package. The required hardware can be built at a relatively low cost compared with commercially available solutions, from off-the-shelf components. Our graphical user interface-based software provides great experimental flexibilit...

Nicotine is an addictive drug whose popularity has recently increased, particularly among adolescents, because of the availability of electronic nicotine devices (i.e., “vaping”) and nicotine e-liquids containing additives with rich chemosensory properties. Some efforts to understand the role of these additives in nicotine reward suggest that they increase nicotine reward and reinforcement, but the sensory contributions of additives, especially in their vapor forms, are largely untested. Here, to better understand how a fruit-flavored (i.e., strawberry) additive influences nicotine reward and aversion, we used a conditioned place preference (CPP) procedure in which nicotine and a strawberry additive were delivered as a vapor to male and female adolescent mice. We found that nicotine vapor alone can lead to a dose-dependent CPP when using a biased design. The strawberry additive did not produce CPP on its own, and we did not observe an effect of the strawberry additive on nicotine vapor-induced reward. Neve...

Native speakers excel at parsing continuous speech into smaller elements and entraining their neural activities to the linguistic hierarchy at different levels (e.g., syllables, phrases, and sentences) to achieve speech comprehension. However, how a nonnative brain tracks hierarchical linguistic structures in second language (L2) speech comprehension and whether it relates to top-down attention and language proficiency remains elusive. Here, we applied a frequency-tagging paradigm in human adults and investigated the neural tracking responses to hierarchically organized linguistic structures (i.e., the syllabic rate of 4 Hz, the phrasal rate of 2 Hz, and the sentential rate of 1 Hz) in both first language (L1) and L2 listeners when they attended to a speech stream or ignored it. We revealed disrupted neural responses to higher-order linguistic structures (i.e., phrases and sentences) for L2 listeners in which the phrasal-level tracking was functionally related to an L2 subject’s language proficiency. We al...

While animal and human decision strategies are typically explained by model-free and model-based reinforcement learning (RL), their choice sequences often follow simple procedures based on working memory (WM) of past actions and rewards. Here, we address how working memory-based choice strategies, such as win-stay-lose-switch (WSLS), are represented in the prefrontal and motor cortico-basal ganglia loops by simultaneous recording of neuronal activities in the dorsomedial striatum (DMS), the dorsolateral striatum (DLS), the medial prefrontal cortex (mPFC), and the primary motor cortex (M1). In order to compare neuronal representations when rats employ working memory-based strategies, we developed a new task paradigm, a continuous/intermittent choice task, consisting of choice and no-choice trials. While the continuous condition (CC) consisted of only choice trials, in the intermittent condition (IC), a no-choice trial was inserted after each choice trial to disrupt working memory of the previous choice and ...

The imagination of tactile stimulation has been shown to activate primary somatosensory cortex (S1) with a somatotopic specificity akin to that seen during the perception of tactile stimuli. Using fMRI and multivariate pattern analysis, we investigate whether this recruitment of sensory regions also reflects content-specific activation (i.e., whether the activation in S1 is specific to the mental content participants imagined). To this end, healthy volunteers ( n  = 21) either perceived or imagined three types of vibrotactile stimuli (mental content) while fMRI data were acquired. Independent of the content, during tactile mental imagery we found activation of frontoparietal regions, supplemented with activation in the contralateral BA2 subregion of S1, replicating previous reports. While the imagery of the three different stimuli did not reveal univariate activation differences, using multivariate pattern classification, we were able to decode the imagined stimulus type from BA2. Moreover, cross-classific...