eNeuro最新文献

The relationships between facial expression and color affect human cognition functions such as perception and memory. However, whether these relationships influence selective attention and brain activity contributed to selective attention remains unclear. For example, reddish angry faces increase emotion intensity, but it is unclear whether brain activity and selective attention are similarly enhanced. To investigate these questions, we examined whether event-related potentials for faces vary depending on facial expression and color by recording electroencephalography (EEG) data. We conducted an oddball task using stimuli that combined facial expressions (angry, neutral) and facial colors (original, red, green). The participants counted the number of times a rarely appearing target face stimulus appeared among the standard face stimuli. The results indicated that the difference in P3 amplitudes for the target and standard faces depended on the combinations of facial expressions and facial colors; the P3 for red angry faces were greater than those for red neutral faces. Additionally, facial expression or facial color had no significant main effect or interaction effect on P1 amplitudes for the target, and facial expression had significant main effects only on the N170 amplitude. These findings suggest that the interaction between facial expression and color modulates the P3 associated with selective attention. Moreover, the response enhancement resulting from this interaction appears to occur at a cognitive processing stage that follows the processing stage associated with facial color or expression alone. Our results support the idea that red color increases the human response to anger from an EEG perspective.

The social environment has long been recognized to play an important role in substance use, which is often modeled in rodents using operant conditioning. However, most operant chambers only accommodate one rodent at a time. We present PeerPub-a unique social operant chamber. PeerPub employs touch sensors to track the licking behavior on drinking spouts. When the number of licks meets a set reinforcement schedule, it dispenses a drop of solution with a fixed volume as a reward at the tip of the spout. A radio frequency identification (RFID) chip implanted in each rat's skull identifies it throughout the experiment. The system is managed by a Raspberry Pi computer. We evaluated PeerPub using Sprague Dawley rats in daily 1 h sessions, where supersac (a glucose and saccharin solution) was provided under a fixed-ratio five schedule. We discovered that male rats consumed more supersac in dual rat conditions compared with single rat conditions. These findings illustrate PeerPub's effectiveness in modeling the interaction between motivated behavior and social context. We expect devices like PeerPub will help highlight the role of social environments in substance use disorder phenotypes. All computer code, 3D design, and build instructions for PeerPub can be found at http://github.com/nijie321/PeerPub.

The full complement of ion channels which influence insect auditory mechanotransduction and the mechanisms by which their influence is exerted remain unclear. Shal (K_v4), a Shaker family member encoding voltage-gated potassium channels in Drosophila melanogaster, has been shown to localize to dendrites in some neuron types, suggesting the potential role of Shal in Drosophila hearing, including mechanotransduction. A GFP trap was used to visualize the localization of the Shal channel in Johnston's organ neurons responsible for hearing in the antenna. Shal protein was localized strongly to the cell body and inner dendritic segment of sensory neurons. It was also detectable in the sensory cilium, suggesting its involvement not only in general auditory function but specifically in mechanotransduction. Electrophysiological recordings to assess neural responses to auditory stimuli in mutant Shal flies revealed significant decreases in auditory responses. Laser Doppler vibrometer recordings indicated abnormal antennal free fluctuation frequencies in mutant lines, indicating an effect on active antennal tuning, and thus active transduction mechanisms. This suggests that Shal participates in coordinating energy-dependent antennal movements in Drosophila that are essential for tuning the antenna to courtship song frequencies.

Status epilepticus (SE) links to high mortality and morbidity. Considering the neuroprotective property of baicalein (BA), we investigated its effects on post-SE neuronal injury via the NLRP3/GSDMD pathway. Mice were subjected to SE modeling and BA interference, with seizure severity and learning and memory abilities evaluated. The histological changes, neurological injury and neuron-specific enolase (NSE)-positive cell number in hippocampal CA1 region, and cell death were assessed. Levels of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3)/gasdermin-D (GSDMD) pathway-related proteins, inflammatory factors, and Iba-1 + NLRP3+ and Iba-1 + GSDMD-N+ cells were determined. BA ameliorated post-SE cognitive dysfunction and neuronal injury in mice, as evidenced by shortened escape latency, increased number of crossing the target quadrant within 60 s and the time staying in the target quadrant, alleviated hippocampal damage, increased viable cell number, decreased neuronal injury, and increased NSE-positive cells. Mechanistically, BA repressed microglial pyroptosis, reduced inflammatory factor release, and attenuated neuronal injury by inhibiting the NLRP3/GSDMD pathway. The NLRP3 inhibitor exerted similar effects as BA on SE mice, while the NLRP3 activator partially reversed BA-improved post-SE neuronal injury in mice. Conjointly, BA reduced microglial pyroptosis in hippocampal CA1 area by inhibiting the NLRP3/GSDMD pyroptosis pathway, thereby ameliorating post-SE neuronal injury in mice.

Brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) are known to contribute to both protective and pronociceptive processes. However, their contribution to neuropathic pain after spinal cord injury (SCI) needs further investigation. In a recent study utilizing TrkB^F616A mice, it was shown that systemic pharmacogenetic inhibition of TrkB signaling with 1NM-PP1 (1NMP) immediately after SCI delayed the onset of pain hypersensitivity, implicating maladaptive TrkB signaling in pain after SCI. To examine potential neural mechanisms underlying the behavioral outcome, patch-clamp recording was performed in small-diameter dissociated thoracic (T) dorsal root ganglia (DRG) neurons to evaluate TrkB signaling in uninjured mice and after T10 contusion SCI. Bath-applied 7,8-dihydroxyflavone (7,8-DHF), a selective TrkB agonist, induced a robust inward current in neurons from uninjured mice, which was attenuated by 1NMP treatment. SCI also decreased 7,8-DHF-induced current while increasing the latency to its peak amplitude. Western blot revealed a concomitant decrease in TrkB expression in DRGs adjacent to the spinal lesion. Analyses of cellular and membrane properties showed that SCI increased neuronal excitability, evident by an increase in resting membrane potential and the number of spiking neurons. However, SCI did not increase spontaneous firing in DRG neurons. These results suggest that SCI induced changes in TrkB activation in DRG neurons even though these alterations are likely not contributing to pain hypersensitivity by nociceptor hyperexcitability. Overall, this reveals complex interactions involving TrkB signaling and provides an opportunity to investigate other, presumably peripheral, mechanisms by which TrkB contributes to pain hypersensitivity after SCI.

Cuprizone (CPZ) is a widely used toxin that induces demyelinating diseases in animal models, producing multiple sclerosis (MS)-like pathology in rodents. CPZ is one of the few toxins that triggers demyelination and subsequent remyelination following the cessation of its application. This study examines the functional consequences of CPZ-induced demyelination and the subsequent recovery of neural communication within the anterior cingulate cortex (ACC), with a particular focus on inter-hemispheric connectivity via the corpus callosum. By employing wide-field, high-speed, voltage-sensitive dye imaging, we were able to provide real-time mapping of neural activity in the ACC of CPZ-fed mice. Although we could not record physiological signals from the corpus callosum, the results demonstrated a notable impairment in inter-hemispheric connections within the ACC via the corpus callosum, with the most pronounced loss observed in a specific coronal slice among a series of slices examined. Notably, the latency of neural signal propagation remained largely unaltered despite connectivity loss, indicating that demyelination affects the extent, rather than the temporal dynamics, of neural communication. It is noteworthy that while functional connectivity appeared to recover fully after the cessation of CPZ, histological analysis revealed only partial recovery of myelination, indicating a discrepancy between functional and structural recovery. These findings enhance our understanding of how demyelination affects the ACC's role in orchestrating neural activity, particularly in light of the slice-specific nature of interhemispheric communication impairments. These findings offer new insights into MS pathology, particularly regarding the role of the corpus callosum in interhemispheric communication and potential therapeutic strategies.Significance Statement Cuprizone (CPZ) is widely used to model multiple sclerosis in rodents by inducing demyelination. While the demyelination effects of CPZ have been widely studied, this study explores CPZ's impact on the prefrontal cortex (PFC). Using voltage-sensitive dye imaging (VSDI), we identified disruptions in PFC connectivity within and between hemispheres in CPZ-fed mice, though signal timing remained unaffected. This finding suggests that demyelination impairs connectivity without slowing transmission speed. Remarkably, connectivity restoration aligned with brain remyelination, providing insights into recovery pathways in MS.

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 between cell type and isoform expression. Vast mRNA isoform diversity was observed in all 50 targeted genes, even those that were not differentially expressed in the short-read data. We also developed an informatics method for detection of isoform structural differences in novel isoforms versus the reference annotation. These data expand available single-cell datasets of the human prefrontal cortical transcriptome with combined short- and long-read sequencing across AD, DLB, and PD, revealing increased mRNA isoform diversity that may contribute to disease features and could potentially represent therapeutic targets for neurodegenerative diseases.

Preterm infants are at risk for brain injury and neurodevelopmental impairment due, in part, to white matter injury following chronic hypoxia exposure. However, the precise molecular mechanisms by which neonatal hypoxia disrupts early neurodevelopment are poorly understood. Here, we constructed a brain-wide map of the regenerative response to newborn brain injury using high-resolution imaging-based spatial transcriptomics to analyze over 800,000 cells in a mouse model of chronic neonatal hypoxia. Additionally, we developed a new method for inferring condition-associated differences in cell type spatial proximity, enabling the identification of niche-specific changes in cellular architecture. We observed hypoxia-associated changes in region-specific cell states, cell type composition, and spatial organization. Importantly, our analysis revealed mechanisms underlying reparative neurogenesis and gliogenesis, while also nominating pathways that may impede circuit rewiring following neonatal hypoxia. Altogether, our work provides a comprehensive description of the molecular response to newborn brain injury.

Reported associations between functional connectivity and affective disorder symptoms are minimally reproducible, which can partially be attributed to difficulty capturing highly variable clinical symptoms in cross-sectional study designs. "Dense sampling" protocols, where participants are sampled across multiple sessions, can overcome this limitation by studying associations between functional connectivity and variable clinical states. Here, we characterized effect sizes for the association between functional connectivity and time-varying positive and negative daily affect in a nonclinical cohort. Data were analyzed from 24 adults who attended four research visits, where participants self-reported daily affect using the PANAS-X questionnaire and completed 39 min of functional magnetic resonance imaging across three passive viewing conditions. We modeled positive and negative daily affect in relation to network-level functional connectivity, with hypotheses regarding within-network connectivity of the default mode, salience/cingulo-opercular, frontoparietal, dorsal attention, and visual networks and between-network connectivity of affective subcortical regions (amygdala and nucleus accumbens) with both default mode and salience/cingulo-opercular networks. Effect sizes for associations between affect and network-level functional connectivity were small and nonsignificant across analyses. We additionally report that functional connectivity variance is largely attributable to individual identity with small relative variance (<3%) accounted for by within-subject daily affect variation. These results support previous reports that functional connectivity is dominated by stable subject-specific connectivity patterns, while additionally suggesting relatively minimal influence of day-to-day affect. Researchers planning studies examining functional connectivity in relation to daily affect, or other varying stable states, should therefore anticipate small effect sizes and carefully consider power in study planning.

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 directionally selective, and 28% were omnidirectionally responsive. In contrast, at 1,024°/s, 20% of the cells were directionally selective, and nearly half of the population was omnidirectionally responsive. Only 15% of the cells were omnidirectionally excited across most speeds. The remaining 85% of the cells had direction tuning that changed with speed. Collectively, these results indicate a shift from a bias for directional tuning at intermediate speeds of global visual motion to a bias for omnidirectional responses at faster speeds. These results suggest a potential role for the pretectum during flight by detecting unexpected drift or potential collisions, depending on the speed of the optic flow signal.