JNEUROSCI (ISSN 0270-6474) 是神经科学学会的官方期刊。它由协会每周出版，一年五十周，一年一卷。 JNEUROSCI 发表的论文涉及神经系统研究人员普遍感兴趣的广泛主题。作者现在可以为其发表的文章提供开放选择选项

The Journal of Neuroscience (ISSN 0270-6474) is the official journal of the Society for Neuroscience. It is published weekly, with fifty issues per year, forming one volume annually. The journal publishes papers covering a wide range of topics of interest to researchers in the field of neuroscience. Authors now have the option to provide open access for their published articles.

《Journal of Neuroscience》（ISSN 0270-6474）是神经科学学会的官方期刊。该期刊每周出版一次，每年出版五十期，形成一卷。期刊发表的论文涵盖了神经系统研究领域的广泛主题，旨在满足研究人员的兴趣。此外，作者现在可以为其发表的文章选择开放获取选项。

Journal of Neuroscience

Sound deprivation by conductive hearing loss increases hearing thresholds, but little is known about the response of the auditory brainstem during and after conductive hearing loss. Here, we show in young adult rats that 10 d of monaural conductive hearing loss (i.e., earplugging) leads to hearing deficits that persist after sound levels are restored. Hearing thresholds in response to clicks and frequencies higher than 8 kHz remain increased after a 10 d recovery period. Neural output from the cochlear nucleus measured at 10 dB above threshold is reduced and followed by an overcompensation at the level of the lateral lemniscus. We assessed whether structural and molecular substrates at auditory nerve (endbulb of Held) synapses in the cochlear nucleus could explain these long-lasting changes in hearing processing. During earplugging, vGluT1 expression in the presynaptic terminal decreased and synaptic vesicles were smaller. Together, there was an increase in postsynaptic density (PSD) thickness and an upregulation of GluA3 AMPA receptor subunits on bushy cells. After earplug removal and a 10 d recovery period, the density of synaptic vesicles increased, vesicles were also larger, and the PSD of endbulb synapses was larger and thicker. The upregulation of the GluA3 AMPAR subunit observed during earplugging was maintained after the recovery period. This suggests that GluA3 plays a role in plasticity in the cochlear nucleus. Our study demonstrates that sound deprivation has long-lasting alterations on structural and molecular presynaptic and postsynaptic components at the level of the first auditory nerve synapse in the auditory brainstem.
SIGNIFICANCE STATEMENTDespite being the second most prevalent form of hearing loss, conductive hearing loss and its effects on central synapses have received relatively little attention. Here, we show that 10 d of monaural conductive hearing loss leads to an increase in hearing thresholds, to an increased central gain upstream of the cochlear nucleus at the level of the lateral lemniscus, and to long-lasting presynaptic and postsynaptic structural and molecular effects at the endbulb of the Held synapse. Knowledge of the structural and molecular changes associated with decreased sensory experience, along with their potential reversibility, is important for the treatment of hearing deficits, such as hyperacusis and chronic otitis media with effusion, which is prevalent in young children with language acquisition or educational disabilities.

Cheryl Clarkson

Flora M. Antunes

Maria E. Rubio

The Journal of Neuroscience

J. Neurosci.

Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus

传导性听力损失对耳蜗核听神经突触前和突触后结构具有长期结构和分子影响

Individuals use both passive and active defensive responses to environmental threats. Much is known about the neural circuits of passive defensive responses (e.g., freezing), but less is known about the substrates of active defensive responses (e.g., avoidance). We developed an active avoidance task in which rats learn to avoid a tone-signaled footshock by stepping onto a nearby platform. An advantage of this task is that freezing, which can interfere with avoidance, is reduced, thereby facilitating comparison of the effects of manipulations on avoidance versus freezing. After 10 d of avoidance training, rats were infused with muscimol to pharmacologically inactivate the prelimbic cortex (PL), infralimbic cortex (IL), ventral striatum (VS), or basolateral amygdala (BLA). Inactivating PL, VS, or BLA all impaired avoidance expression, but these areas differed with respect to freezing. Inactivating BLA decreased freezing consistent with loss of the tone–shock association, whereas inactivation of VS increased freezing consistent with loss of avoidance memory. Inactivation of PL had no effect on freezing. Inactivation of IL did not impair avoidance expression but did impair avoidance extinction. Our findings suggest that active avoidance is mediated by prefrontal–striatal circuits, which may be overactive in individuals suffering from trauma-related disorders.

Christian Bravo-Rivera

Ciorana Roman-Ortiz

Edith Brignoni-Perez

Francisco Sotres-Bayon

Gregory J. Quirk

Neural Structures Mediating Expression and Extinction of Platform-Mediated Avoidance

There is a growing body of research demonstrating that the cerebellum is involved in language understanding. Early theories assumed that the cerebellum is involved in low-level language processing. However, those theories are at odds with recent work demonstrating cerebellar activation during cognitive tasks. Using natural language stimuli and an encoding model framework, we performed an fMRI experiment on 3 men and 2 women, where subjects passively listened to 5 h of natural language stimuli, which allowed us to analyze language processing in the cerebellum with higher precision than previous work. We used these data to fit voxelwise encoding models with five different feature spaces that span the hierarchy of language processing from acoustic input to high-level conceptual processing. Examining the prediction performance of these models on separate BOLD data shows that cerebellar responses to language are almost entirely explained by high-level conceptual language features rather than low-level acoustic or phonemic features. Additionally, we found that the cerebellum has a higher proportion of voxels that represent social semantic categories, which include “social” and “people” words, and lower representations of all other semantic categories, including “mental,” “concrete,” and “place” words, than cortex. This suggests that the cerebellum is representing language at a conceptual level with a preference for social information. SIGNIFICANCE STATEMENT Recent work has demonstrated that, beyond its typical role in motor planning, the cerebellum is implicated in a wide variety of tasks, including language. However, little is known about the language representations in the cerebellum, or how those representations compare to cortex. Using voxelwise encoding models and natural language fMRI data, we demonstrate here that language representations are significantly different in the cerebellum compared with cortex. Cerebellum language representations are almost entirely semantic, and the cerebellum contains overrepresentation of social semantic information compared with cortex. These results suggest that the cerebellum is not involved in language processing per se, but cognitive processing more generally.

Amanda LeBel

Shailee Jain

Alexander G. Huth

Voxelwise Encoding Models Show That Cerebellar Language Representations Are Highly Conceptual

Commonly prescribed selective serotonin reuptake inhibitors (SSRIs) inhibit the serotonin transporter to correct a presumed deficit in extracellular serotonin signaling during depression. These agents bring clinical relief to many who take them; however, a significant and growing number of individuals are resistant to SSRIs. There is emerging evidence that inflammation plays a significant role in the clinical variability of SSRIs, though how SSRIs and inflammation intersect with synaptic serotonin modulation remains unknown. In this work, we use fast in vivo serotonin measurement tools to investigate the nexus between serotonin, inflammation, and SSRIs. Upon acute systemic lipopolysaccharide (LPS) administration in male and female mice, we find robust decreases in extracellular serotonin in the mouse hippocampus. We show that these decreased serotonin levels are supported by increased histamine activity (because of inflammation), acting on inhibitory histamine H3 heteroreceptors on serotonin terminals. Importantly, under LPS-induced histamine increase, the ability of escitalopram to augment extracellular serotonin is impaired because of an off-target action of escitalopram to inhibit histamine reuptake. Finally, we show that a functional decrease in histamine synthesis boosts the ability of escitalopram to increase extracellular serotonin levels following LPS. This work reveals a profound effect of inflammation on brain chemistry, specifically the rapidity of inflammation-induced decreased extracellular serotonin, and points the spotlight at a potentially critical player in the pathology of depression, histamine. The serotonin/histamine homeostasis thus, may be a crucial new avenue in improving serotonin-based treatments for depression. SIGNIFICANCE STATEMENT Acute LPS-induced inflammation (1) increases CNS histamine, (2) decreases CNS serotonin (via inhibitory histamine receptors), and (3) prevents a selective serotonin reuptake inhibitor (SSRI) from effectively increasing extracellular serotonin. A targeted depletion of histamine recovers SSRI-induced increases in extracellular hippocampal serotonin.

Melinda Hersey

Srimal Samaranayake

Shane N. Berger

Navid Tavakoli

Sergio Mena

H. Frederik Nijhout

Michael C. Reed

Janet Best

Randy D. Blakely

Lawrence P. Reagan

Parastoo Hashemi

Inflammation-Induced Histamine Impairs the Capacity of Escitalopram to Increase Hippocampal Extracellular Serotonin

The glymphatic system is a brainwide CSF transport system that uses the perivascular space for fast inflow of CSF. Arterial pulsations are a major driver of glymphatic CSF inflow, and hypertension that causes vascular pathologies, such as arterial stiffening and perivascular alterations, may impede the inflow. We used dynamic contrast-enhanced MRI to assess the effect of hypertension on glymphatic transport kinetics in male young and adult spontaneously hypertensive (SHR) rats compared with age-matched normotensive Wistar-Kyoto rats (WKY). We anesthetized the rats with dexmedetomidine/isoflurane and infused paramagnetic contrast (Gd-DOTA) into the cisterna magna during dynamic contrast-enhanced MRI to quantify glymphatic transport kinetics. Structural MRI analysis showed that cerebroventricular volumes are larger and brain volumes significantly smaller in SHR compared with WKY rats, regardless of age. We observed ventricular reflux of Gd-DOTA in SHR rats only, indicating abnormal CSF flow dynamics secondary to innate hydrocephalus. One-tissue compartment analysis revealed impeded glymphatic transport of Gd-DOTA in SHR compared with WKY rats in both age groups, implying that glymphatic transport, including solute clearance from brain parenchyma, is impaired during evolving hypertension in young SHR, an effect that worsens in states of chronic hypertension. The study demonstrates the suppression of glymphatic clearance in SHR rats and thus offers new insight into the coexistence of hypertension and concomitant vascular pathologies in Alzheimer9s disease. The study further highlights the importance of considering the distribution of tracers in the CSF compartment in the analysis of the glymphatic system. SIGNIFICANCE STATEMENT The glymphatic system contributes to the removal of amyloid β from the brain and is disrupted in Alzheimer9s disease and aging. Using a rat model of hypertension, we measured gross CSF flow and tracked glymphatic influx and efflux rates with dynamic contrast-enhanced MRI, showing that glymphatic transport is compromised in both early and advanced stages of hypertension. The study provides a new perspective on the importance for brain metabolite and fluid homeostasis of maintaining healthy blood vessels, an increasingly pertinent issue in an aging population that in part may explain the link between vascular pathology and Alzheimer9s disease.

Kristian Nygaard Mortensen

Simon Sanggaard

Humberto Mestre

Hedok Lee

Serhii Kostrikov

Anna L.R. Xavier

Albert Gjedde

Helene Benveniste

Maiken Nedergaard

Impaired Glymphatic Transport in Spontaneously Hypertensive Rats

The nervous system contains complex circuits comprising thousands of cell types and trillions of connections. Here, we discuss how the field of “developmental systems neuroscience” combines the molecular and genetic perspectives of developmental neuroscience with the (typically adult-focused) functional perspective of systems neuroscience. This combination of approaches is critical to understanding how a handful of cells eventually produce the wide range of behaviors necessary for survival. Functional circuit development typically lags behind neural connectivity, leading to intermediate stages of neural activity that are either not seen in adults or, if present, are considered pathophysiological. Developmental systems neuroscience examines these intermediate stages of neural activity, mapping out the critical phases and inflection points of neural circuit function to understand how neural activity and behavior emerge across development. Beyond understanding typical development, this approach provides invaluable insight into the pathophysiology of neurodevelopmental disorders by identifying when and how functional development diverges between health and disease. We argue that developmental systems neuroscience will identify important periods of neural development, reveal novel therapeutic windows for treatment, and set the stage to answer fundamental questions about the brain in health and disease.

James C. Dooley

Meike E. van der Heijden

More Than a Small Brain: The Importance of Studying Neural Function during Development

不仅仅是小脑：研究发育过程中神经功能的重要性

Although neurosciences have made notable progress in theory and technology, a significant methodological issue persists with the continued reliance on homogeneous sample groups (Burns et al., 2019). This observation is neither new nor recent, as several authors have already raised concerns about the fact that behavioral scientists base their conclusions mostly on samples composed almost exclusively of people from Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies, even though these groups are very peculiar, representing only 12% of all humans and may be considered outliers (Henrich et al., 2010). The problem is exacerbated by the frequent use of convenience samples, which tend to consist primarily of university students, resulting in a narrower demographic range that fails to represent the broader diversity within society. The inclusion of more diverse populations is crucial, notably in light of the nature versus nurture debate. It is indeed now widely accepted that both cultural and biological factors contribute to shaping human psychology and behaviors (Chiao and Ambady, 2007). However, the lack of diversity in population samples diminishes the impact of cultural (nurture) factors in the obtained results and makes it difficult to claim whether neurocognitive processes are universal or culture specific (Burns et al., 2019). Beyond cultural differences, the lack of access to diverse populations can hinder the exploration of innovative research questions in the field, which may require targeting specific populations that use, for instance, different metric systems, have unique hierarchical structures, or have experienced a unique historical event. A critical question thus remains: Why does the pursuit of greater diversity in population samples remain so limited? Part of the answer is undoubtedly tied to the unequal distribution of funding and the number of scientists in specific parts of the world who lack the resources to conduct research … Correspondence should be addressed to Emilie A. Caspar at emilie.caspar{at}ugent.be.

Emilie A. Caspar

Guidelines for Inclusive and Diverse Human Neuroscience Research Practices

包容性和多样化人类神经科学研究实践指南

Loss of a sensory modality triggers global adaptation across brain areas, allowing the remaining senses to guide behavior more effectively. There are specific synaptic and circuit plasticity observed across many sensory areas, which suggests potential widespread changes in activity. Here we used a cFosTRAP2 mouse line to drive tdTomato (tdT) expression in active cells to spatially map the extent of activity changes in various sensory areas in adult mice of both sexes following two modes of visual deprivation. We found that in the primary visual cortex (V1) both dark exposure (DE) and enucleation (EN) caused an initial loss of active cells followed by a partial rebound, which occurred relatively more in the superficial layers. A similar pattern was observed in the secondary visual cortex, especially in the lateral areas (V2L). The spared primary sensory cortices adapted distinctly. In the primary somatosensory barrel cortex (S1BF) there was a change in the density of active cells dependent on the duration and the mode of visual deprivation. In the primary auditory cortex (A1), there was a relative reduction in the density of active cells in the superficial layers without a significant change in the overall density. There were minimal changes in the active cell density in the secondary cortices of the spared senses and the multisensory retrosplenial cortex (RSP). Our results are consistent with cross-modal recruitment of the deprived visual cortex and compensatory plasticity in the spared primary sensory cortices that can support enhanced processing and refinement of the spared senses. Significance Statement The neural basis for improved processing of the spared senses after losing vision is largely dependent on plasticity mechanisms driven by neural activity. Using a transgenic mouse model to label active neurons in a temporally controlled manner, this study reveals the spatial pattern of widespread activity changes across brain areas following visual deprivation in adult mice. The findings suggest that the deprived visual cortex undergoes an initial reduction in activity followed by a rebound suggestive of cross-modal recruitment. Activity changes in the spared primary sensory cortices conform to compensatory plasticity, which could support improved processing of the spared senses. The results highlight the presence of large-scale plasticity in the adult brain to compensate for loss of vision.

Samuel Parkins

Yidong Song

Yanis Jaoui

Aryan Gala

Kaven T. Konda

Crispo Richardson

Hey-Kyoung Lee

Spatial mapping of activity changes across sensory areas following visual deprivation in adults

成人视觉剥夺后感觉区域活动变化的时空图谱

Although the therapeutic potential of miRNA-mediated gene regulation has been investigated, its precise functional regulatory mechanism in neuropathic pain remains incompletely understood. In this study, we elucidate that miR-216a-3p serves as a critical non-coding RNA involved in the modulation of trigeminal-mediated neuropathic pain. By conducting RNA-seq and qPCR analysis, we observed a notable decrease of miR-216a-3p in the injured trigeminal ganglia (TG) of male rats. Intra-TG administration of miR-216a-3p agomir or lentiviral-mediated overexpression of miR-216a-3p specifically in sensory neurons of injured TGs alleviated established neuropathic pain behaviors, while downregulation of miR-216a-3p (pharmacologically or genetically) in naïve rats induced pain behaviors. Moreover, nerve injury significantly elevated the H3K27 trimethylation (H3K27me3) levels in the ipsilateral TG, thereby suppressing the SRY-box transcription factor 10 (SOX10) binding to the miR-216a-3p promoter and resulting in the reduction of miR-216a-3p. Inhibiting the enzymes that responsible for catalyzing H3K27me3 restored the nerve injury-induced reduction in miR-216a-3p expression and markedly ameliorated neuropathic pain behaviors. Furthermore, miR-216a-3p targeted stromal interaction molecule 1 (STIM1), and the decreased miR-216a-3p associated with neuropathic pain caused a significant upregulation in the protein abundance of STIM1. Conversely, overexpression of miR-216a-3p in the injured TG suppressed the upregulation of STIM1 expression and reversed the mechanical allodynia. Together, the mechanistic understanding of H3K27me3-dependent SOX10/miR-216a-3p/STIM1 signaling axial in sensory neurons may facilitate the discovery of innovative therapeutic strategies for neuropathic pain management. Significance Statement miRNAs are posttranscriptional regulators of gene expression that play critical roles in the pathogenesis of neuropathic pain. However, the detailed mechanisms by which most pain-associated miRNAs operate and their therapeutic potential are incompletely understood. Our present study revealed that nerve injury-induced trimethylation of lysine 27 on histone H3 (H3K27me3) reduces the binding of SOX10, a transcription factor, to the promoter region of the miR-216a-3p gene, leading to decreased expression of the microRNA, miR-216a-3p. This reduction subsequently promotes neuropathic pain by regulating STIM1. Given that miRNA-mediated gene regulation is a proposed therapeutic approach for treating neuropathic pain, our findings suggest that replenishing miR-216a-3p could serve as a novel strategy for treating chronic neuropathic pain.

Yufang Sun

Yu Tao

Junping Cao

Yaqun Zhang

Zitong Huang

Shoupeng Wang

Weiwei Lu

Qi Zhu

Lidong Shan

Dongsheng Jiang

Yuan Zhang

Jin Tao

H3K27 trimethylation-mediated downregulation of miR-216a-3p in sensory neurons regulates neuropathic pain behaviors via targeting STIM1

H3K27三甲基化介导的感觉神经元中miR-216a-3p下调通过靶向STIM1调控神经病理性疼痛行为

Estimating the motion of objects in depth is important for behavior, and is strongly supported by binocular visual cues. To understand both how the brain should estimate motion in depth and how natural constraints shape and limit performance in two local 3D motion tasks, we develop image-computable ideal observers from a large number of binocular video clips created from a dataset of natural images. The observers spatio-temporally filter the videos, and non-linearly decode 3D motion from the filter responses. The optimal filters and decoder are dictated by the task-relevant image statistics, and are specific to each task. Multiple findings emerge. First, two distinct filter subpopulations are spontaneously learned for each task. For 3D speed estimation, filters emerge for processing either changing disparities over time (CDOT) or interocular velocity differences (IOVD), cues that are used by humans. For 3D direction estimation, filters emerge for discriminating either left-right or towards-away motion. Second, the filter responses, conditioned on the latent variable, are well-described as jointly Gaussian, and the covariance of the filter responses carries the information about the task-relevant latent variable. Quadratic combination is thus necessary for optimal decoding, which can be implemented by biologically plausible neural computations. Finally, the ideal observer yields non-obvious–and in some cases counter-intuitive–patterns of performance like those exhibited by humans. Important characteristics of human 3D motion processing and estimation may therefore result from optimal information processing in the early visual system. Significance statement Humans and other animals extract and process features of natural images that are useful for estimating motion-in-depth, an ability that is crucial for successful interaction with the environment. But the enormous diversity of natural visual inputs that are consistent with a given 3D motion–natural stimulus variability–presents a challenging computational problem. The neural populations that support the estimation of motion-in-depth are under active investigation. Here, we study how to optimally estimate local 3D motion with naturalistic stimulus variability. We show that the optimal computations are biologically plausible, and that they reproduce sometimes counterintuitive performance patterns independently reported in the human psychophysical literature. Novel testable hypotheses for future neurophysiological and psychophysical research are discussed.

Daniel Herrera-Esposito

Johannes Burge

Optimal estimation of local motion-in-depth with naturalistic stimuli

自然刺激下局部深度运动的优化估计

Abbreviation	J. Neurosci.
Journal Impact	4.25
Quartiles(Global)	NEUROSCIENCES(Q1)

ISSN	0270-6474, 1529-2401
h-index	503
Top Journals	Yes

Publication Information	Publisher: Society for Neuroscience，Publishing cycle: Weekly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1981，Proportion of original research papers: 99.68%，Self Citation Rate:4.50%， Gold OA Rate: 73.45%
Average review cycle	网友分享经验：平均12.0个月
Average recruitment ratio	网友分享经验：约20%

Journal of Neuroscience

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