In the article “Comprehensive Characterization of a Subfamily of Ca2+-Binding Proteins in Mouse and Human Retinal Neurons at Single-Cell Resolution” by Jun-Bin Liu, He-Lan Yuan, Gong Zhang, and Jiang-Bin Ke …

Zebrafish have gained prominence as a model organism in neuroscience over the past several decades, generating key insight into the development and functioning of the vertebrate brain. However, techniques for whole-brain mapping in adult stage zebrafish are lacking. Here, we describe a pipeline built using open-source tools for whole-brain activity mapping in adult zebrafish. Our pipeline combines advances in histology, microscopy, and machine learning to capture c-fos activity across the entirety of the brain. Following tissue clearing, whole-brain images are captured using light-sheet microscopy and registered to the recently created adult zebrafish brain atlas (AZBA) for automated segmentation. By way of example, we used our pipeline to measure brain activity after zebrafish were subject to the novel tank test, one of the most widely used behaviors in adult zebrafish. c-fos levels peaked 15 min following behavior and several regions, including those containing serotoninergic and dopaminergic neurons, we...

Alexander disease (AxD) is a rare neurological disorder caused by dominant gain-of-function mutations in the gene for glial fibrillary acidic protein. Expression of mutant protein results in astrocyte dysfunction that ultimately leads to developmental delay, failure to thrive, and intellectual and motor impairment. The disease is typically fatal, and at present there are no preventative or effective treatments. To gain a better understanding of the link between astrocyte dysfunction and behavioral deficits in AxD, we have recently developed a rat model that recapitulates many of the clinical features of the disease, including failure to thrive, motor impairment, and white matter deficits. In the present study, we show that both male and female AxD model rats exhibit a neurodegenerative profile with a progressive neuroinflammatory response combined with reduced expression of synaptic and mitochondrial proteins. Consistent with these results, AxD rats show reduced hippocampal long-term potentiation and are c...

Binocular disparity is used for perception and action in three dimensions. Neurons in the primary visual cortex respond to binocular disparity in random dot patterns, even when the contrast is inverted between eyes (false depth cue). In contrast, neurons in the ventral stream largely cease to respond to false depth cues. This study evaluated whether GABAergic inhibition is involved in suppressing false depth cues in the human ventral visual cortex. We compared GABAergic inhibition (GABA+) and glutamatergic excitation (Glx) during the viewing of correlated and anticorrelated binocular disparity in 18 participants using single-voxel proton magnetic resonance spectroscopy. Measurements were taken from the early visual cortex (EVC) and the lateral occipital cortex (LO). Three visual conditions were presented per voxel location: correlated binocular disparity, anticorrelated binocular disparity, or a blank gray screen with a fixation cross. To identify differences in neurochemistry, GABA+ or Glx levels were com...

The external globus pallidus (GPe) is a central part of the basal ganglia indirect pathway implicated in movement and decision-making. As a hub connecting the dorsal striatum and subthalamic nucleus (STN), the GPe guides repetitive and routine behaviors. However, it remains unknown how diverse GPe cells engage in routine formation while learning action sequences in repetitive reward-seeking conditioning. Here, in male mice, we investigated the Ca2+ dynamics of two GPe cell types, astrocytes and parvalbumin-expressing neurons, during routine formation. Our findings show that the dynamics of GPe astrocytes may be involved in action sequence refinement, a characteristic potentially contributing to more efficient reward-seeking behavior.

Neuroligins (NLGNs) are a family of postsynaptic adhesion molecules that bind to their presynaptic partners, neurexins, facilitating the formation and maintenance of synapses. In humans, there are five genes encoding NLGNs ( NLGN1-3 , NLGN4X , and NLGN4Y ), with NLGN1-3 having highly conserved counterparts in rodents, allowing these genes to be studied with high confidence of translational validity in mouse models. Human NLGN4X and 4Y were often assumed to serve similar functions because they share a 97% sequence homology, whereas mouse NLGN4-like is quite divergent. Many NLGN-mediated synaptic effects are modulated through post-translation modifications, which exert temporal and spatial control. In this report, we characterize a conserved phosphorylation site, serine 712, on NLGN4X and 4Y. Despite serine 712 being located in a highly conserved region between NLGN4X and 4Y, we observed kinase specificity. PKA exclusively phosphorylates NLGN4X S712, whereas Cdk5 phosphorylates S712 on both NLGN4X and 4Y. NL...

Epilepsy, affecting millions globally, often leads to significant cognitive and psychiatric comorbidities, particularly in children. Anxiety and depression are particularly prevalent, with roughly a quarter of pediatric epilepsy patients having a comorbid diagnosis. Current treatments inadequately address these issues. Adrenocorticotropic hormone (ACTH), a melanocortin peptide, has shown promise in mitigating deficits after early-life seizures (ELS), potentially through mechanisms beyond its canonical action on the melanocortin 2 receptor. This study explores the hypothesis that recurrent ELS is associated with long-term anxiety and that treatment with ACTH can prevent this anxiety through a mechanism that involves the melanocortin 4 receptor (MC4R) in the brain. Our findings reveal that ACTH ameliorates anxiety-like behavior associated with ELS, without altering seizure parameters, in wild-type but not in male and female MC4R knock-out mice. Our findings also show that knocking-in MC4R in either neurons o...

Central sensitization plays a critical role in bladder pain syndrome/interstitial cystitis (BPS/IC). Electroacupuncture (EA) nerve stimulation therapy has been broadly acknowledged as an effective means of alleviating chronic pathological pain. However, it remains to be explored whether EA is effective in mitigating pain-sensitive symptoms of BPS/IC and the mechanisms involved. This study aims to investigate the analgesic effect and mechanism of EA therapy. We employed several techniques: mechanical pain threshold tests to assess pain sensitivity, urodynamic studies to evaluate bladder function, western blotting for protein analysis, immunofluorescence for visualizing, and transcriptomics. A rat cystitis model was established through a systemic intraperitoneal injection with cyclophosphamide (CYP). EA therapy was executed by stimulating the deep part of the hypochondriac point. EA treatment was observed to effectively reduce mechanical allodynia, enhance urinary function, suppress the activation of microgl...

Motor skill learning enables organisms to interact effectively with their environment, relying on neural mechanisms that integrate sensory feedback with motor output. While sensory feedback, such as auditory cues linked to motor actions, enhances motor performance in humans, its mechanism of action is poorly understood. Developing a reliable animal model of augmented motor skill learning is crucial to begin dissecting the biological systems that underpin this enhancement. We hypothesized that continuous auditory feedback during a motor task would promote complex motor skill acquisition in mice. We developed a closed-loop system using DeepLabCut for real-time markerless tracking of mouse forepaw movements with high processing speed and low latency. By encoding forepaw movements into auditory tones of different frequencies, mice received continuous auditory feedback during a reaching task requiring vertical displacement of the left forepaw to a target. Adult mice were trained over 4 d with either auditory fe...

Anterior–posterior interactions in the alpha band (8–12 Hz) have been implicated in various functions including perception, attention, and working memory. The underlying neural communication can be flexibly controlled by adjusting phase relations when activities across anterior–posterior regions oscillate at a matched frequency. We thus investigated how alpha oscillation frequencies spontaneously converged along anterior–posterior regions by tracking oscillatory EEG activity while participants rested. As more anterior–posterior regions (scalp sites) frequency-converged, the probability of additional regions joining the frequency convergence increased, and so did oscillatory synchronization (i.e., oscillatory power) at participating regions, suggesting that anterior–posterior frequency convergences are driven by inter-regional entrainment. Notably, frequency convergences were accompanied by two types of approximately linear phase gradients, one progressively phase lagged in the anterior direction, the poste...