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...

Vestibulospinal neurons integrate sensed imbalance to regulate postural reflexes. As an evolutionarily conserved neural population, understanding their synaptic and circuit-level properties can offer insight into vertebrate antigravity reflexes. Motivated by recent work, we set out to verify and extend the characterization of vestibulospinal neurons in the larval zebrafish. Using current-clamp recordings together with stimulation, we observed that larval zebrafish vestibulospinal neurons are silent at rest, yet capable of sustained spiking following depolarization. Neurons responded systematically to a vestibular stimulus (translation in the dark); responses were abolished after chronic or acute loss of the utricular otolith. Voltage-clamp recordings at rest revealed strong excitatory inputs with a characteristic multimodal distribution of amplitudes, as well as strong inhibitory inputs. Excitatory inputs within a particular mode (amplitude range) routinely violated refractory period criteria and exhibited...

Ketamine, an NMDA antagonist, is widely used in clinical settings. Recently, low-dose ketamine has gained attention because of its promising role as a rapid antidepressant. However, the effects of low-dose ketamine on brain function, particularly higher cognitive functions of primate brains, are not fully understood. In this study, we used two macaques as subjects and found that acute low-dose ketamine administration significantly impaired the ability for arbitrary visuomotor mapping (AVM), a form of associative learning (AL) essential for flexible behaviors, including executions of learned stimuli-response contingency or learning of new contingencies. We conducted in-depth analyses and identified intrinsic characteristics of these ketamine-induced functional deficits, including lowered accuracy, prolonged time for planning and movement execution, increased tendency to make errors when visual cues are changed from trial to trial, and stronger impact on combining associative learning and another key higher ...

It is well known that both hand movements and mental representations of movement lead to event-related desynchronization (ERD) of the electroencephalogram (EEG) recorded over the corresponding cortical motor areas. However, the relationship between ERD in somatosensory cortical areas and mental representations of tactile sensations is not well understood. In this study, we employed EEG recordings in healthy humans to compare the effects of real and imagined vibrotactile stimulation of the right hand. Both real and imagined sensations produced contralateral ERD patterns, particularly in the μ-band and most significantly in the C3 region. Building on these results and the previous literature, we discuss the role of tactile imagery as part of the complex body image and the potential for using EEG patterns induced by tactile imagery as control signals in brain-computer interfaces (BCIs). Combining this approach with motor imagery (MI) could improve the performance of BCIs intended for rehabilitation of sensori...

Despite their involvement in many cognitive functions, β oscillations are among the least understood brain rhythms. Reports on whether the functional role of β is primarily inhibitory or excitatory have been contradictory. Our framework attempts to reconcile these findings and proposes that several β rhythms co-exist at different frequencies. β Frequency shifts and their potential influence on behavior have thus far received little attention. In this human magnetoencephalography (MEG) experiment, we asked whether changes in β power or frequency in auditory cortex and motor cortex influence behavior (reaction times) during an auditory sweep discrimination task. We found that in motor cortex, increased β power slowed down responses, while in auditory cortex, increased β frequency slowed down responses. We further characterized β as transient burst events with distinct spectro-temporal profiles influencing reaction times. Finally, we found that increased motor-to-auditory β connectivity also slowed down respo...

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...