Increasing data suggest a crucial relationship between glycolipid metabolic disorder and neuropsychiatric injury. The aim of this study is to investigate the behavioral performance changes and neuropathological injuries in mice challenged with high-fat diet (HFD) and streptozotocin (STZ). The glucose metabolism indicators and behavioral performance were detected. The mRNA expression of IL-1β, IL-6, TNF-α, ocln, zo-1, and clnds and protein expression of APP, p-Tau, p-IRS1, p-AKT, p-ERK, and TREM1/2 were measured. The fluorescence intensities of MAP-2, NeuN, APP, p-Tau, GFAP, and IBA-1 were observed. The results showed that combination of HFD and STZ/I.P. could induce glucose metabolic turmoil and Alzheimer's disease (AD)-like neuropsychiatric dysfunction in mice, as indicated by the increased concentrations of fasting blood glucose and impaired learning and memory ability. Moreover, the model mice presented increased levels of APP, p-Tau, p-IRS1, TREM2, IL-1β, IL-6, TNF-α, ocln, zo-1, and clnds; decreased l...

Single-nucleus RNA-sequencing (snRNA-seq) has revealed new levels of cellular organization and diversity within the human brain. However, full-length mRNA isoforms are not resolved in typical snRNA-seq analyses using short-read sequencing that cannot capture full-length transcripts. Here we combine standard 10x Genomics short-read snRNA-seq with targeted PacBio long-read snRNA-seq to examine isoforms of genes associated with neurological diseases at the single-cell level from prefrontal cortex samples of diseased and nondiseased human brain, assessing over 165,000 cells. Samples from 25 postmortem donors with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), or Parkinson's disease (PD), along with age-matched controls, were compared. Analysis of the short-read libraries identified shared and distinct gene expression changes across the diseases. The same libraries were then assayed using enrichment probes to target 50 disease-related genes followed by long-read PacBio sequencing, enabling linkage b...

In an effort to increase access to neuroscience education in underserved communities, we created an educational program that utilizes a simple task to measure place preference of the cockroach ( Gromphadorhina portentosa ) and the open-source free software, SLEAP Estimates Animal Poses (SLEAP) to quantify behavior. Cockroaches ( n  = 18) were trained to explore a linear track for 2 min while exposed to either air, vapor, or vapor with nicotine from a port on one side of the linear track over 14 d. The time the animal took to reach the port was measured, along with distance traveled, time spent in each zone, and velocity. As characterizing behavior is challenging and inaccessible for nonexperts new to behavioral research, we created an educational program using the machine learning algorithm, SLEAP, and cloud-based (i.e., Google Colab) low-cost platforms for data analysis. We found that SLEAP was within a 0.5% margin of error when compared with manually scoring the data. Cockroaches were found to have an in...

Maintaining concentration on demanding cognitive tasks, such as vigilance (VG) and working memory (WM) tasks, is crucial for successful task completion. Previous research suggests that internal concentration maintenance fluctuates, potentially declining to suboptimal states, which can influence trial-by-trial performance in these tasks. However, the timescale of such alertness maintenance, as indicated by slow changes in pupil diameter, has not been thoroughly investigated. This study explored whether “pupil trends”—which selectively signal suboptimal tonic alertness maintenance at various timescales—negatively correlate with trial-by-trial performance in VG and WM tasks. Using the psychomotor vigilance task (VG) and the visual–spatial two-back task (WM), we found that human pupil trends lasting over 10 s were significantly higher in trials with longer reaction times, indicating poorer performance, compared with shorter reaction time trials, which indicated better performance. The attention network test fu...

Chromatin regulation plays a crucial role in neocortical neurogenesis, and mutations in chromatin modifiers are linked to neurodevelopmental disorders. RBBP4 is a core subunit of several chromatin-modifying complexes; however, its functional role and genome-wide occupancy profile in the neocortical primordium are unknown. To address this, we performed RBBP4 knockdown using CRISPR/Cas9 on neocortical progenitors derived from mice of both sexes at embryonic age 12.5 during deep layer neurogenesis. Our study demonstrates that downregulation of RBBP4 in the E12.5 neocortical progenitors reduced neuronal output, specifically affecting CTIP2-expressing neurons. We demonstrate that RBBP4 plays an essential role in regulating neocortical progenitor proliferation. However, overexpression of RBBP4 alone was not sufficient to regulate neuronal fate. Genome-wide occupancy analysis revealed that RBBP4 primarily binds to distal regulatory elements, and neuron differentiation is a significant GO biological pathway of RBB...

When making perceptual decisions, humans combine information across sensory modalities dependent on their respective uncertainties. However, it remains unknown how the brain integrates multisensory feedback during movement and which factors besides sensory uncertainty influence sensory contributions. We performed two reaching experiments on healthy adults to investigate whether movement corrections to combined visual and mechanical perturbations scale with visual uncertainty. To describe the dynamics of multimodal feedback responses, we further varied movement time and visual feedback duration during the movement. The results of our first experiment show that the contribution of visual feedback decreased with uncertainty. Additionally, we observed a transient phase during which visual feedback responses were stronger during faster movements. In a follow-up experiment, we found that the contribution of vision increased more quickly during slow movements when we presented the visual feedback for a longer tim...

Autism spectrum disorder (ASD) is characterized by deficits in social interaction and communication, cognitive rigidity, and atypical sensory processing. Recent studies suggest that the basal ganglia, specifically the striatum (NSt), plays an important role in ASD. While striatal interneurons, including cholinergic (ChAT+) and parvalbumin-positive (PV+) GABAergic neurons, have been described to be altered in animal models of ASD, their specific contribution remains elusive. Here, we combined behavioral, anatomical, and electrophysiological quantifications to explore if interneuron balance could be implicated in atypical sensory processing in cortical and striatal somatosensory regions of rats subjected to a valproic acid (VPA) model of ASD. We found that VPA animals showed a significant decrease in the number of ChAT+ and PV+ cells in multiple regions (including the sensorimotor region) of the NSt. We also observed significantly different sensory-evoked responses at the single-neuron and population levels ...

Goal-directed actions require transforming sensory information into motor plans defined across multiple parameters and reference frames. Substantial evidence supports the encoding of target direction in gaze- and body-centered coordinates within parietal and premotor regions. However, how the brain encodes the equally critical parameter of target distance remains less understood. Here, using Bayesian pattern component modeling of fMRI data during a delayed reach-to-target task, we dissociated the neural encoding of both target direction and the relative distances between target, gaze, and hand at early and late stages of motor planning. This approach revealed independent representations of direction and distance along the human dorsomedial reach pathway. During early planning, most premotor and superior parietal areas encoded a target’s distance in single or multiple reference frames and encoded its direction. In contrast, distance encoding was magnified in gaze- and body-centric reference frames during la...

Overexpression of the eukaryotic initiation factor 4E ( eIF4E ) gene has been associated with excessive stereotypic behaviors and reduced sociability, which manifest as autism-like social cognitive deficits. However, the precise mechanisms by which eIF4E overexpression insufficiently induces these autism-like behaviors and the specific brain regions implicated remain insufficiently understood. Oxytocin (OXT), a neurotransmitter known for its role in social behavior, has been proposed to modulate certain autism-related symptoms by influencing microglial function and attenuating neuroinflammation. Nonetheless, the contributions of the hippocampus and oxytocin in the content of eIF4E overexpression-induced autistic behaviors remain elucidated. To investigate this issue, researchers utilized the three-chamber social interaction test, the open-field test, and the Morris water maze to evaluate the social cognitive behaviors of the two groups of mice. Additionally, ELISA, immunofluorescence, Western blotting, and...

The pretectum of vertebrates contains neurons responsive to global visual motion. These signals are sent to the cerebellum, forming a subcortical pathway for processing optic flow. Global motion neurons exhibit selectivity for both direction and speed, but this is usually assessed by first determining direction preference at intermediate velocity (16–32°/s) and then assessing speed tuning at the preferred direction. A consequence of this approach is that it is unknown if and how direction preference changes with speed. We measured directional selectivity in 114 pretectal neurons from 44 zebra finches ( Taeniopygia guttata ) across spatial and temporal frequencies, corresponding to a speed range of 0.062–1,024°/s. Pretectal neurons were most responsive at 32–64°/s with lower activity as speed increased or decreased. At each speed, we determined if cells were directionally selective, bidirectionally selective, omnidirectionally responsive, or unmodulated. Notably, at 32°/s, 60% of the cells were directionall...