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A Prefrontal→Periaqueductal Gray Pathway Differentially Engages Autonomic, Hormonal, and Behavioral Features of the Stress-Coping Response. 前额叶-大脑皮质灰质通路以不同方式参与压力应对反应的自律神经、荷尔蒙和行为特征。
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-13 DOI: 10.1523/JNEUROSCI.0844-24.2024
Timothy D Skog, Shane B Johnson, Dalton C Hinz, Ryan T Lingg, Emily N Schulz, Jordan T Luna, Terry G Beltz, Sara A Romig-Martin, Stephanie C Gantz, Baojian Xue, Alan K Johnson, Jason J Radley

The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes. Optogenetic excitation of the rostral medial prefrontal cortex (mPFC) input to the ventrolateral periaqueductal gray (vlPAG) decreased passive behavior (immobility), attenuated the glucocorticoid hormone response, but did not prevent arterial pressure and heart rate increases associated with rats' active behavioral (defensive burying) engagement during the SPDB. In contrast, inhibition of the same pathway increased behavioral immobility and attenuated hemodynamic output but did not affect glucocorticoid increases. Further analyses confirmed that hemodynamic increments occurred preferentially during active behaviors and decrements during immobility epochs, whereas pathway manipulations, regardless of the directionality of effect, weakened these correlational relationships. Finally, neuroanatomical evidence indicated that the influence of the rostral mPFC→vlPAG pathway on coping response patterns is mediated predominantly through GABAergic neurons within vlPAG. These data highlight the importance of this prefrontal→midbrain connection in organizing stress-coping responses and in coordinating bodily systems with behavioral output for adaptation to aversive experiences.

自律神经系统和下丘脑-垂体-肾上腺(HPA)系统的激活与不同环境需求下的行为调整相互依存。然而,对压力反应神经基础的啮齿类实验室研究通常认为,无论采用主动还是被动的应对策略,这些系统的增量都是单一的。利用冲击探针防御性掩埋试验(SPDB)自然地测量雄性和雌性大鼠的应激应对特征,我们确定了一种神经通路,在这种通路中,活动变化可能会促进血液动力学和 HPA 指数的独特反应模式,从而将主动和被动应对表型典型化。光遗传激发喙内侧前额叶皮层(mPFC)对腹外侧uctal灰质(vlPAG)的输入会减少被动行为(不动),减弱糖皮质激素反应,但不会阻止动脉压和心率的增加,而这与大鼠在 SPDB 期间的主动行为(防御性掩埋)有关。相比之下,抑制相同的通路会增加行为的不稳定性并减弱血液动力学输出,但不会影响糖皮质激素的增加。相关性分析证实,血液动力的增加主要发生在活跃行为中,而减少则发生在不活跃行为中。最后,神经解剖学证据表明,喙mPFC-vlPAG通路对应对反应模式的影响主要是通过vlPAG内的GABA能神经元介导的。这些数据强调了前额叶与中脑之间的这种联系在组织压力应对反应以及协调身体系统与行为输出以适应厌恶体验方面的重要性。然而,人们对大脑皮层控制应对方式的神经生物学基础知之甚少。我们揭示了前额叶到文丘外侧uctal 灰色通路在调节大鼠主动与被动压力应对模式中的新作用。光遗传激发这条通路可降低行为被动性,减弱应激诱导的糖皮质激素增加,但并不能阻止自律神经输出的相关增加。抑制该通路会增加行为被动性,减弱自律神经输出,但不会影响糖皮质激素的增加。这些数据强调了前额叶与中脑的联系在组织压力应对反应以及协调身体系统与行为输出以适应厌恶体验方面的重要性。
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引用次数: 0
Neural Predictors of Fear Depend on the Situation. 神经对恐惧的预测取决于具体情况。
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-13 DOI: 10.1523/JNEUROSCI.0142-23.2024
Yiyu Wang, Philip A Kragel, Ajay B Satpute

The extent to which neural representations of fear experience depend on or generalize across the situational context has remained unclear. We systematically manipulated variation within and across three distinct fear-evocative situations including fear of heights, spiders, and social threats. Participants (n = 21; 10 females and 11 males) viewed ∼20 s clips depicting spiders, heights, or social encounters and rated fear after each video. Searchlight multivoxel pattern analysis was used to identify whether and which brain regions carry information that predicts fear experience and the degree to which the fear-predictive neural codes in these areas depend on or generalize across the situations. The overwhelming majority of brain regions carrying information about fear did so in a situation-dependent manner. These findings suggest that local neural representations of fear experience are unlikely to involve a singular pattern but rather a collection of multiple heterogeneous brain states.

恐惧体验的神经表征在多大程度上依赖于情境或在多大程度上泛化于情境,目前仍不清楚。我们对三种不同的恐惧诱发情境(包括恐高、蜘蛛和社会威胁)内部和之间的变化进行了系统化处理。参与者(n=21,10 名女性和 11 名男性)观看了 20 秒左右的蜘蛛、高处或社交场合的视频短片,并在每段视频后对恐惧感进行评分。研究人员使用探照灯多象素模式分析(MVPA)来确定是否有哪些脑区携带有预测恐惧体验的信息,以及这些脑区的恐惧预测神经代码在多大程度上依赖于不同的情境或在不同情境中具有普遍性。绝大多数携带恐惧信息的脑区都是以依赖情境的方式携带恐惧信息的。这些研究结果表明,恐惧体验的局部神经表征不太可能是一种单一的模式,而是多种异质大脑状态的集合。我们在此提供的证据表明,最近的恐惧神经特征中广泛分布的激活模式反映了功能异质的大脑状态的组合。受试者完成了一项新颖的 fMRI 任务,该任务参数化地检查了三种内容丰富的自然情境中和情境间的主观恐惧:恐高、蜘蛛和社会威胁。利用探照灯分析和机器学习方法,我们发现绝大多数预测恐惧的脑区只在特定情况下预测恐惧。这些发现对跨物种恐惧研究结果的推广、恐惧和焦虑的转化模型以及恐惧神经特征的开发具有重要意义。
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引用次数: 0
Deciphering Peripheral Taste Neuron Diversity: Using Genetic Identity to Bridge Taste Bud Innervation Patterns and Functional Responses. 解密外周味觉神经元的多样性:利用基因特性连接味蕾神经支配模式和功能反应。
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-13 DOI: 10.1523/JNEUROSCI.0583-24.2024
Lisa C Ohman, Tao Huang, Victori A Unwin, Aditi Singh, Brittany Walters, Zachary D Whiddon, Robin F Krimm

Peripheral taste neurons exhibit functional, genetic, and morphological diversity, yet understanding how or if these attributes combine into taste neuron types remains unclear. In this study, we used male and female mice to relate taste bud innervation patterns to the function of a subset of proenkephalin-expressing (Penk+) taste neurons. We found that taste arbors (the portion of the axon within the taste bud) stemming from Penk+ neurons displayed diverse branching patterns and lacked stereotypical endings. The range in complexity observed for individual taste arbors from Penk+ neurons mirrored the entire population, suggesting that taste arbor morphologies are not primarily regulated by the neuron type. Notably, the distinguishing feature of arbors from Penk+ neurons was their propensity to come within 110 nm (in apposition with) different types of taste-transducing cells within the taste bud. This finding is contrary to the expectation of genetically defined taste neuron types that functionally represent a single stimulus. Consistently, further investigation of Penk+ neuron function revealed that they are more likely to respond to innately aversive stimuli-sour, bitter, and high salt concentrations-as compared with the full taste population. Penk+ neurons are less likely to respond to nonaversive stimuli-sucrose, umami, and low salt-compared with the full population. Our data support the presence of a genetically defined neuron type in the geniculate ganglion that is responsive to innately aversive stimuli. This implies that genetic expression might categorize peripheral taste neurons into hedonic groups, rather than simply identifying neurons that respond to a single stimulus.

外周味觉神经元表现出功能、遗传和形态的多样性,但这些属性如何或是否结合成味觉神经元类型仍不清楚。在这项研究中,我们利用雄性和雌性小鼠将味蕾神经支配模式与表达原脑啡肽(Penk+)的味觉神经元亚群的功能联系起来。我们发现,源于 Penk+ 神经元的味觉轴突(味蕾内的轴突部分)显示出多种多样的分支模式,并且缺乏定型末梢。在来自 Penk+ 神经元的单个味觉轴上观察到的复杂性范围反映了整个群体的情况,这表明味觉轴形态主要不受神经元类型的调节。值得注意的是,来自 Penk+ 神经元的树轴的显著特征是它们倾向于与味蕾内不同类型的味觉传导细胞在 110 nm 范围内(贴靠)。这一发现与基因定义的味觉神经元类型在功能上代表单一刺激的预期相反。同样,对 Penk+ 神经元功能的进一步研究发现,与全部味觉神经元相比,Penk+ 神经元更有可能对酸味、苦味和高浓度盐味等先天厌恶性刺激做出反应。与全部味觉群体相比,Penk+神经元对蔗糖、鲜味和低盐等非厌恶性刺激的反应较少。我们的数据支持在膝状神经节中存在一种基因定义的神经元类型,这种神经元对天生的厌恶刺激有反应。这意味着基因表达可能会将外周味觉神经元划分为对冲性神经元群,而不是简单地识别对单一刺激做出反应的神经元。我们的研究通过利用特定神经元亚群的基因表达,将外周神经支配模式与功能性味觉反应联系起来,从而深入探讨了这一问题。我们研究了一种味觉神经元类型,它似乎与多种味觉传导细胞类型相联系,并对天生厌恶的酸味、苦味和高浓度氯化钠刺激做出反应。这些综合观察结果表明,遗传标记可以划分出具有相似味觉反应的神经元群,而不是仅仅根据单个味觉品质对神经元进行分类。
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引用次数: 0
Encoding of Vibrotactile Stimuli by Mechanoreceptors in Rodent Glabrous Skin. 啮齿动物无毛皮肤机械感受器对振动触觉刺激的编码
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-13 DOI: 10.1523/JNEUROSCI.1252-24.2024
Laura Medlock, Dhekra Al-Basha, Adel Halawa, Christopher Dedek, Stéphanie Ratté, Steven A Prescott

Somatosensory coding in rodents has been mostly studied in the whisker system and hairy skin, whereas the function of low-threshold mechanoreceptors (LTMRs) in the rodent glabrous skin has received scant attention, unlike in primates where the glabrous skin has been the focus. The relative activation of different LTMR subtypes carries information about vibrotactile stimuli, as does the rate and temporal patterning of LTMR spikes. Rate coding depends on the probability of a spike occurring on each stimulus cycle (reliability), whereas temporal coding depends on the timing of spikes relative to the stimulus cycle (precision). Using in vivo extracellular recordings in male rats and mice of either sex, we measured the reliability and precision of LTMR responses to tactile stimuli including sustained pressure and vibration. Similar to other species, rodent LTMRs were separated into rapid-adapting (RA) or slow-adapting based on their response to sustained pressure. However, unlike the dichotomous frequency preference characteristic of RA1 and RA2/Pacinian afferents in other species, rodent RAs fell along a continuum. Fitting generalized linear models to experimental data reproduced the reliability and precision of rodent RAs. The resulting model parameters highlight key mechanistic differences across the RA spectrum; specifically, the integration window of different RAs transitions from wide to narrow as tuning preferences across the population move from low to high frequencies. Our results show that rodent RAs can support both rate and temporal coding, but their heterogeneity suggests that coactivation patterns play a greater role in population coding than for dichotomously tuned primate RAs.

对啮齿类动物体感编码的研究主要集中在胡须系统和有毛皮肤上,而对啮齿类动物无毛皮肤上的低阈机械感受器(LTMR)的功能却很少关注,这与灵长类动物无毛皮肤是研究重点不同。不同 LTMR 亚型的相对激活以及 LTMR 尖峰的速率和时间模式都含有振动触觉刺激的信息。速率编码取决于每个刺激周期出现尖峰的概率(可靠性),而时间编码则取决于尖峰相对于刺激周期的时间(精确性)。通过对雄性大鼠和雌性小鼠进行体内细胞外记录,我们测量了LTMR对触觉刺激(包括持续压力和振动)反应的可靠性和精确性。与其他物种类似,啮齿动物的 LTMR 也根据其对持续压力的反应分为快速适应型(RA)和慢速适应型(SA)。然而,与其他物种中 RA1 和 RA2/Pacinian 传入器的二分频率偏好特征不同,啮齿动物的 RA 沿着一个连续体分布。将广义线性模型(GLM)拟合到实验数据中,再现了啮齿动物 RA 的可靠性和精确性。由此得出的模型参数凸显了整个 RA 频谱的关键机制差异;具体来说,随着整个种群的调谐偏好从低频向高频移动,不同 RA 的整合窗口也从宽阔过渡到狭窄。我们的研究结果表明,啮齿类动物的RA既能支持速率编码,也能支持时间编码,但它们的异质性表明,与二分调谐的灵长类RA相比,共激活模式在群体编码中发挥着更大的作用。尽管在其他物种(如灵长类动物)中各种纤维类型的反应特性已得到充分证实,但在大鼠和小鼠中的定量特征描述却很有限。为了填补这一空白,我们对啮齿动物无毛皮肤触觉纤维的编码特性进行了全面的电生理学研究,然后模拟了这些纤维,以解释其反应的差异。我们的研究表明,啮齿动物的触觉纤维与其他物种的触觉纤维相似,但它们在群体水平上的异质性可能有所不同,这对触觉编码可能具有重要影响。模拟揭示了支持这种异质性的内在机制,并为探索啮齿动物的躯体感觉提供了有用的工具。
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引用次数: 0
Cell-type-specific splicing of transcription regulators and Ptbp1 by Rbfox1/2/3 in the developing neocortex. 在发育中的新皮层中,Rbfox1/2/3对转录调节因子和Ptbp1进行细胞类型特异性剪接。
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-12 DOI: 10.1523/JNEUROSCI.0822-24.2024
Xiangbin Ruan, Kaining Hu, Yalan Yang, Runwei Yang, Elizabeth Tseng, Bowei Kang, Aileen Kauffman, Rong Zhong, Xiaochang Zhang

How master splicing regulators crosstalk with each other and to what extent transcription regulators are differentially spliced remain unclear in the developing brain. Here, cell-type-specific RNA-Seq analyses of the developing neocortex uncover variable expression of the Rbfox1/2/3 genes and enriched splicing events in transcription regulators, altering protein isoforms or inducing nonsense-mediated mRNA decay. Transient expression of Rbfox proteins in radial glial progenitors induces neuronal splicing events preferentially in transcription regulators such as Meis2 and Tead1 Surprisingly, Rbfox proteins promote the inclusion of a mammal-specific alternative exon and a previously undescribed poison exon in Ptbp1 Simultaneous ablation of Rbfox1/2/3 in the neocortex downregulates neuronal isoforms and disrupts radial neuronal migration. Furthermore, the progenitor isoform of Meis2 promotes Tgfb3 transcription, while the Meis2 neuron isoform promotes neuronal differentiation. These observations indicate that transcription regulators are differentially spliced between cell types in the developing neocortex. [The sex has not been reported to affect cortical neurogenesis in mice, and embryos of both sexes were studied without distinguishing one or the other.]Significance Statement How alternative splicing regulates cell-type-specific gene expression in the developing neocortex remains understudied. Here, analyses of sorted cell types and single-cell long-reads uncover cell-type-specific splicing that is enriched in transcription regulators. Rbfox proteins, including the pan-neuronal marker NeuN/Rbfox3, preferentially switch splice forms of transcription regulators and are required for radial neuronal migration. We further show that the progenitor and neuron isoforms of a transcription regulator Meis2 function differently. Overall, this study suggests a cross-talk between alternative splicing and transcription for neuronal gene regulation.

在发育中的大脑中,主剪接调控因子如何相互影响以及转录调控因子在多大程度上被不同程度地剪接仍不清楚。在这里,对发育中的新皮质进行的细胞类型特异性 RNA-Seq 分析发现了 Rbfox1/2/3 基因的可变表达以及转录调节因子的丰富剪接事件,这些事件改变了蛋白质的同工型或诱导了无义介导的 mRNA 衰减。在径向神经胶质祖细胞中瞬时表达 Rbfox 蛋白会诱导神经元剪接事件,这些事件主要发生在 Meis2 和 Tead1 等转录调节因子中,令人惊讶的是,Rbfox 蛋白会促进 Ptbp1 中哺乳动物特异性替代外显子和以前未描述过的毒外显子的包含。此外,Meis2的祖细胞同工酶促进Tgfb3的转录,而Meis2的神经元同工酶则促进神经元的分化。这些观察结果表明,转录调节因子在发育中的新皮层细胞类型之间存在不同的剪接。[意义声明 替代剪接如何调节发育中的新皮质中细胞类型特异性基因的表达仍未得到充分研究。在这里,对分类细胞类型和单细胞长读数的分析发现了细胞类型特异性剪接,这种剪接富含转录调节因子。Rbfox蛋白(包括泛神经元标记物NeuN/Rbfox3)优先切换转录调节因子的剪接形式,并且是径向神经元迁移所必需的。我们进一步发现,转录调节因子 Meis2 的祖细胞和神经元异构体具有不同的功能。总之,这项研究表明,神经元基因调控的替代剪接和转录之间存在交叉对话。
{"title":"Cell-type-specific splicing of transcription regulators and <i>Ptbp1</i> by <i>Rbfox1/2/3</i> in the developing neocortex.","authors":"Xiangbin Ruan, Kaining Hu, Yalan Yang, Runwei Yang, Elizabeth Tseng, Bowei Kang, Aileen Kauffman, Rong Zhong, Xiaochang Zhang","doi":"10.1523/JNEUROSCI.0822-24.2024","DOIUrl":"10.1523/JNEUROSCI.0822-24.2024","url":null,"abstract":"<p><p>How master splicing regulators crosstalk with each other and to what extent transcription regulators are differentially spliced remain unclear in the developing brain. Here, cell-type-specific RNA-Seq analyses of the developing neocortex uncover variable expression of the Rbfox1/2/3 genes and enriched splicing events in transcription regulators, altering protein isoforms or inducing nonsense-mediated mRNA decay. Transient expression of Rbfox proteins in radial glial progenitors induces neuronal splicing events preferentially in transcription regulators such as <i>Meis2</i> and <i>Tead1</i> Surprisingly, Rbfox proteins promote the inclusion of a mammal-specific alternative exon and a previously undescribed poison exon in <i>Ptbp1</i> Simultaneous ablation of <i>Rbfox1/2/3</i> in the neocortex downregulates neuronal isoforms and disrupts radial neuronal migration. Furthermore, the progenitor isoform of <i>Meis2</i> promotes <i>Tgfb3</i> transcription, while the <i>Meis2</i> neuron isoform promotes neuronal differentiation. These observations indicate that transcription regulators are differentially spliced between cell types in the developing neocortex. [The sex has not been reported to affect cortical neurogenesis in mice, and embryos of both sexes were studied without distinguishing one or the other.]<b>Significance Statement</b> How alternative splicing regulates cell-type-specific gene expression in the developing neocortex remains understudied. Here, analyses of sorted cell types and single-cell long-reads uncover cell-type-specific splicing that is enriched in transcription regulators. Rbfox proteins, including the pan-neuronal marker NeuN/Rbfox3, preferentially switch splice forms of transcription regulators and are required for radial neuronal migration. We further show that the progenitor and neuron isoforms of a transcription regulator <i>Meis2</i> function differently. Overall, this study suggests a cross-talk between alternative splicing and transcription for neuronal gene regulation.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diverse frontoparietal connectivity supports semantic prediction and integration in sentence comprehension. 不同的额叶连接支持句子理解中的语义预测和整合。
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-12 DOI: 10.1523/JNEUROSCI.1404-24.2024
Yaji He, Ximing Shao, Chang Liu, Chen Fan, Elizabeth Jefferies, Meichao Zhang, Xiaoqing Li

Predictive processing in parietal, temporal, frontal, and sensory cortex allows us to anticipate future meanings to maximize the efficiency of language comprehension, with the temporoparietal junction (TPJ) and inferior frontal gyrus (IFG) thought to be situated towards the top of a predictive hierarchy. Although the regions underpinning this fundamental brain function are well-documented, it remains unclear how they interact to achieve efficient comprehension. To this end we recorded functional magnetic resonance imaging (fMRI) in 22 participants (11 males) while they comprehended sentences presented part-by-part, in which we manipulated the constraint provided by sentential contexts on upcoming semantic information. Using this paradigm, we examined the connectivity patterns of bilateral TPJ and IFG during anticipatory phases (i.e., before the onset of targets) and integration phases (i.e., after the onset of targets). When upcoming semantic content was highly predictable in strong-constraint contexts, both left TPJ and bilateral IFG showed stronger visual coupling, while right TPJ showed stronger connectivity with regions within control, default mode, and visual networks, including IFG, parahippocampal gyrus, posterior cingulate, and fusiform gyrus. These connectivity patterns were weaker when predicted semantic content appeared, in line with predictive coding theory. Conversely, for less predictable content, these connectivity patterns were stronger during the integration phase. Overall, these results suggest that both top-down semantic prediction and bottom-up integration during predictive processing are supported by flexible coupling of frontoparietal regions with control, memory, and sensory systems.Significance Statement Recent work has revealed the neural basis of predictive language comprehension. However, it remains unclear how brain regions change their connectivity in a dynamic fashion to support comprehension in highly predictive and less predictive contexts. Here, we show that stronger frontoparietal connectivity with cognitive control, memory, and sensory areas supports top-down prediction generation in strong-constraint contexts; these connectivity patterns are reduced when the anticipated information appears. This pattern is reversed when upcoming sensory input is unpredictable; connectivity is stronger after word inputs have been presented, allowing semantic integration with preceding low-constraint context. Our findings suggest that both top-down semantic prediction and bottom-up semantic integration in language comprehension rely upon diverse functional coupling of higher-order frontoparietal regions with other brain systems.

顶叶、颞叶、额叶和感觉皮层的预测处理使我们能够预测未来的含义,从而最大限度地提高语言理解的效率,而颞顶交界处(TPJ)和额下回(IFG)被认为位于预测层次结构的顶端。尽管支持这一基本大脑功能的区域已被详细记录,但它们如何相互作用以实现高效理解仍不清楚。为此,我们记录了 22 名参与者(11 名男性)在理解逐部分呈现的句子时的功能磁共振成像(fMRI),其中我们操纵了句子上下文对即将出现的语义信息的限制。通过这种范式,我们研究了双侧 TPJ 和 IFG 在预期阶段(即目标出现之前)和整合阶段(即目标出现之后)的连接模式。当即将出现的语义内容在强约束情境中具有高度可预测性时,左侧TPJ和双侧IFG都表现出更强的视觉耦合,而右侧TPJ则表现出与控制、默认模式和视觉网络中的区域(包括IFG、海马旁回、扣带回后部和纺锤形回)更强的连接。当出现可预测的语义内容时,这些连接模式就会减弱,这与预测编码理论是一致的。相反,对于可预测性较低的内容,这些连接模式在整合阶段更强。总之,这些结果表明,在预测处理过程中,自上而下的语义预测和自下而上的整合都是由顶叶前部区域与控制、记忆和感觉系统的灵活耦合支持的。然而,目前仍不清楚大脑区域如何以动态的方式改变其连接性,以支持高预测性和低预测性语境下的理解。在这里,我们发现,在强约束语境中,顶叶前部与认知控制、记忆和感觉区域更强的连通性支持自上而下的预测生成;当预期信息出现时,这些连通性模式会降低。当即将到来的感官输入不可预测时,这种模式就会发生逆转;单词输入出现后,连通性就会增强,从而使语义与之前的低约束语境融合在一起。我们的研究结果表明,语言理解中自上而下的语义预测和自下而上的语义整合都依赖于高阶额顶区与其他大脑系统的不同功能耦合。
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引用次数: 0
Breathing modulates network activity in frontal brain regions during anxiety. 呼吸调节焦虑时额叶脑区的网络活动
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-11 DOI: 10.1523/JNEUROSCI.1191-24.2024
Ana L A Dias, Davi Drieskens, Joseph A Belo, Elis H Duarte, Diego A Laplagne, Adriano B L Tort

Anxiety elicits various physiological responses, including changes in respiratory rate and neuronal activity within specific brain regions such as the medial prefrontal cortex (mPFC). Previous research suggests that the olfactory bulb (OB) modulates the mPFC through respiration-coupled neuronal oscillations (RCOs), which have been linked to fear-related freezing behavior. Nevertheless, the impact of breathing on frontal brain networks during other negative emotional responses, such as anxiety-related states characterized by higher breathing rates, remains unclear. To address this, we subjected rats to the elevated plus maze (EPM) paradigm while simultaneously recording respiration and local field potentials in the OB and mPFC. Our findings demonstrate distinct respiratory patterns during EPM exploration: slower breathing frequencies prevailed in the closed arms, whereas faster frequencies were observed in the open arms, independent of locomotor activity, indicating that anxiety-like states are associated with increased respiratory rates. Additionally, we identified RCOs at different frequencies, mirroring the bimodal distribution of respiratory frequencies. RCOs exhibited higher power during open arm exploration, when they showed greater coherence with breathing at faster frequencies. Furthermore, we confirmed that nasal respiration drives RCOs in frontal brain regions, and found a stronger effect during faster breathing. Interestingly, we observed that the frequency of prefrontal gamma oscillations modulated by respiration increased with breathing frequency. Overall, our study provides evidence for a significant influence of breathing on prefrontal cortex networks during anxious states, shedding light on the complex interplay between respiratory physiology and emotional processing.Significance Statement Understanding how breathing influences brain activity during anxious states could pave the way for novel therapeutic interventions targeting respiratory control to alleviate anxiety symptoms. Our study uncovers a crucial link between respiratory patterns and anxiety-related neural activity in the brain. By investigating the interplay between breathing, neuronal oscillations, and emotional states, we reveal that anxiety induces distinct respiratory patterns, with higher breathing rates correlating with anxious behavior. Importantly, we demonstrate that respiration drives oscillatory activity in the prefrontal cortex, and this effect is potentiated during the fast breathing associated with anxiety. Furthermore, faster breathing modulates the emergence of faster prefrontal gamma oscillations. This discovery sheds new light on the intricate relationship between respiratory physiology and emotional processing.

焦虑会引起各种生理反应,包括呼吸频率和内侧前额叶皮层(mPFC)等特定脑区神经元活动的变化。以前的研究表明,嗅球(OB)通过呼吸耦合神经元振荡(RCOs)调节内侧前额叶皮层(mPFC),而呼吸耦合神经元振荡与恐惧相关的冻结行为有关。然而,在其他负面情绪反应(如以较高呼吸频率为特征的焦虑相关状态)期间,呼吸对额叶大脑网络的影响仍不清楚。为了解决这个问题,我们对大鼠进行了高架加迷宫(EPM)范式实验,同时记录了大鼠大脑外叶和前额叶局部场电位的呼吸情况。我们的研究结果表明,在 EPM 探索过程中,大鼠的呼吸模式截然不同:封闭臂中的呼吸频率较慢,而开放臂中的呼吸频率较快,这与运动活动无关,表明焦虑样状态与呼吸频率增加有关。此外,我们还发现了不同频率的 RCO,反映了呼吸频率的双峰分布。在张臂探索时,RCOs 表现出更高的功率,此时它们与频率较快的呼吸表现出更大的一致性。此外,我们还证实鼻腔呼吸会驱动额叶脑区的 RCOs,并发现在较快的呼吸过程中会产生更强的效应。有趣的是,我们观察到前额叶伽马振荡受呼吸调节的频率随着呼吸频率的增加而增加。总之,我们的研究为焦虑状态下呼吸对前额叶皮层网络的重要影响提供了证据,揭示了呼吸生理与情绪处理之间复杂的相互作用。 重要意义 声明 了解焦虑状态下呼吸如何影响大脑活动可为针对呼吸控制的新型治疗干预措施铺平道路,从而缓解焦虑症状。我们的研究揭示了呼吸模式与大脑中与焦虑相关的神经活动之间的重要联系。通过研究呼吸、神经元振荡和情绪状态之间的相互作用,我们发现焦虑会诱发不同的呼吸模式,较高的呼吸频率与焦虑行为相关。重要的是,我们证明呼吸驱动了前额叶皮层的振荡活动,而这种效应在与焦虑相关的快速呼吸中得到了加强。此外,更快的呼吸会调节更快的前额叶伽马振荡的出现。这一发现揭示了呼吸生理与情绪处理之间错综复杂的关系。
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引用次数: 0
Distinct inhibitory neurons differently shape neuronal codes for sound intensity in the auditory cortex. 不同的抑制性神经元以不同方式形成听觉皮层中声音强度的神经元编码。
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-08 DOI: 10.1523/JNEUROSCI.1502-23.2024
Melanie Tobin, Janaki Sheth, Katherine C Wood, Erin K Michel, Maria N Geffen

Cortical circuits contain multiple types of inhibitory neurons which shape how information is processed within neuronal networks. Here, we asked whether somatostatin-expressing (SST) and vasoactive intestinal peptide-expressing (VIP) inhibitory neurons have distinct effects on population neuronal responses to noise bursts of varying intensities. We optogenetically stimulated SST or VIP neurons while simultaneously measuring the calcium responses of populations of hundreds of neurons in the auditory cortex of male and female awake, head-fixed mice to sounds. Upon SST neuronal activation, noise bursts representations became more discrete for different intensity levels, relying on cell identity rather than strength. By contrast, upon VIP neuronal activation, noise bursts of different intensity level activated overlapping neuronal populations, albeit at different response strengths. At the single-cell level, SST and VIP neuronal activation differentially modulated the response-level curves of monotonic and nonmonotonic neurons. SST neuronal activation effects were consistent with a shift of the neuronal population responses toward a more localist code with different cells responding to sounds of different intensity. By contrast, VIP neuronal activation shifted responses towards a more distributed code, in which sounds of different intensity level are encoded in the relative response of similar populations of cells. These results delineate how distinct inhibitory neurons in the auditory cortex dynamically control cortical population codes. Different inhibitory neuronal populations may be recruited under different behavioral demands, depending on whether categorical or invariant representations are advantageous for the task.Significance Statement Information about sounds is represented in the auditory cortex by neuronal population activity that has a characteristic sparse structure. Cortical neuronal populations comprise multiple types of excitatory and inhibitory neurons. Here, we find that activating different types of inhibitory neurons differentially controls population neuronal representations, with one type of inhibitory neurons increasing the differences in the identity of the cells recruited to represent the different sounds, and another inhibitory neuron type changing the relative activity level of overlapping neuronal populations. Such transformations may be beneficial for different types of auditory behaviors, suggesting that these different types of inhibitory neurons may be recruited under different behavioral constraints in optimizing neuronal representations of sounds.

大脑皮层回路包含多种类型的抑制性神经元,它们决定了神经元网络内的信息处理方式。在这里,我们探讨了表达体生长抑素(SST)和表达血管活性肠肽(VIP)的抑制性神经元是否会对神经元群对不同强度噪声脉冲的反应产生不同的影响。我们对 SST 或 VIP 神经元进行了光遗传刺激,同时测量了头部固定的雌雄清醒小鼠听皮层中数百个神经元群对声音的钙离子反应。当 SST 神经元被激活时,不同强度水平的噪声脉冲表征变得更加离散,这依赖于细胞的特性而非强度。相比之下,VIP神经元激活后,不同强度水平的噪声脉冲会激活重叠的神经元群,尽管反应强度不同。在单细胞水平上,SST 和 VIP 神经元激活对单调和非单调神经元的反应水平曲线有不同的调节作用。SST 神经元激活效应与神经元群反应转向更局部的编码一致,不同细胞对不同强度的声音做出反应。与此相反,VIP 神经元激活则使反应转向更分散的代码,其中不同强度水平的声音被编码在类似细胞群的相对反应中。这些结果描述了听觉皮层中不同的抑制性神经元是如何动态控制皮层群体代码的。在不同的行为需求下,不同的抑制性神经元群可能会被招募,这取决于分类表征或不变表征对任务是否有利。皮层神经元群由多种类型的兴奋性和抑制性神经元组成。在这里,我们发现激活不同类型的抑制性神经元会对群体神经元表征产生不同的控制作用,其中一种抑制性神经元会增加被招募来表征不同声音的细胞身份的差异,而另一种抑制性神经元类型则会改变重叠神经元群体的相对活动水平。这种转变可能有利于不同类型的听觉行为,表明这些不同类型的抑制性神经元可能是在优化声音神经元表征的不同行为限制条件下被招募的。
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引用次数: 0
Unique cortical and subcortical activation patterns for different conspecific calls in marmosets. 狨猴皮层和皮层下对不同同类叫声的独特激活模式
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-08 DOI: 10.1523/JNEUROSCI.0670-24.2024
Azadeh Jafari, Audrey Dureux, Alessandro Zanini, Ravi S Menon, Kyle M Gilbert, Stefan Everling

The common marmoset (Callithrix jacchus) is known for its highly vocal nature, displaying a diverse range of calls. Functional imaging in marmosets has shown that the processing of conspecific calls activates a brain network that includes fronto-temporal areas. It is currently unknown whether different call types activate the same or different networks. In this study, nine adult marmosets (four females) were exposed to four common vocalizations (phee, chatter, trill, and twitter), and their brain responses were recorded using event-related fMRI at 9.4T. We found robust activations in the auditory cortices, encompassing core, belt, and parabelt regions, and in subcortical areas like the inferior colliculus, medial geniculate nucleus, and amygdala in response to these calls. Although a common network was engaged, distinct activity patterns were evident for different vocalizations that could be distinguished by a 3D convolution neural network, indicating unique neural processing for each vocalization. Our findings also indicate the involvement of the cerebellum and medial prefrontal cortex (mPFC) in distinguishing particular vocalizations from others.Significance Statement This study investigates the neural processing of vocal communications in the common marmoset (Callithrix jacchus). Utilizing event-related fMRI at 9.4T, we demonstrate that different calls (phee, chatter, trill, and twitter) elicit distinct brain activation patterns, challenging the notion of a uniform neural network for all vocalizations. Each call type distinctly engages various regions within the auditory cortices and subcortical areas. These findings offer insights into the evolutionary mechanisms of primate vocal perception and provide a foundation for understanding the origins of human speech and language processing.

普通狨猴(Callithrix jacchus)以善于发声而闻名,会发出各种不同的叫声。狨猴的功能成像显示,处理同类叫声会激活一个包括前颞区在内的大脑网络。目前还不清楚不同的叫声会激活相同还是不同的网络。在这项研究中,九只成年狨猴(四只雌性)暴露于四种常见的发声(phee、chatter、trill和twitter),并在9.4T下使用事件相关fMRI记录了它们的大脑反应。我们发现,听觉皮层(包括核心区、带状区和带旁区)以及皮层下区(如下丘、内侧膝状核和杏仁核)在听到这些叫声时会发生强烈激活。虽然有一个共同的网络参与,但不同的发声有明显不同的活动模式,可以通过三维卷积神经网络加以区分,这表明每种发声都有独特的神经处理过程。我们的研究结果还表明,小脑和内侧前额叶皮层(mPFC)参与了区分特定发声和其他发声的过程。 意义声明 本研究调查了普通狨猴(Callithrix jacchus)发声交流的神经处理过程。利用 9.4T 的事件相关 fMRI,我们证明了不同的叫声(phee、chatter、trill 和 twitter)会引起不同的大脑激活模式,这对所有发声都有统一的神经网络这一概念提出了挑战。每种叫声都能明显地调动听皮层和皮层下的不同区域。这些发现有助于深入了解灵长类动物发声感知的进化机制,并为理解人类语音和语言处理的起源奠定了基础。
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引用次数: 0
Differential intrinsic firing properties in sustained and transient mouse alpha RGCs match their light response characteristics and persist during retinal degeneration. 持续性和瞬时性小鼠αRGC固有点燃特性的差异与其光反应特性相匹配,并在视网膜退化过程中持续存在。
IF 4.4 2区 医学 Q1 NEUROSCIENCES Pub Date : 2024-11-08 DOI: 10.1523/JNEUROSCI.1592-24.2024
P Werginz, V Király, G Zeck

Retinal ganglion cells (RGCs) are the neuronal connections between the eye and the brain conveying multiple features of the outside world through parallel pathways. While there is a large body of literature how these pathways arise in the retinal network, the process of converting presynaptic inputs into RGC spiking output is little understood. In this study, we show substantial differences in the spike generator across three types of alpha RGCs in female and male mice, the αON sustained, αOFF sustained and αOFF transient RGC. The differences in their intrinsic spiking responses match the differences of the light responses across RGC types. While sustained RGC types have spike generators that are able to generate sustained trains of action potentials at high rates, the transient RGC type fired shortest action potentials enabling it to fire high-frequency transient bursts. The observed differences were also present in late-stage photoreceptor-degenerated retina demonstrating long-term functional stability of RGC responses even when presynaptic circuitry is deteriorated for long periods of time. Our results demonstrate that intrinsic cell properties support the presynaptic retinal computation and are, once established, independent of them.Significance Statement Spiking output from retinal ganglion cells (RGCs) has long been thought to be solely determined by synaptic inputs from the retinal network. We show that the cell-intrinsic spike generator varies across RGC populations and therefore that postsynaptic processing shapes retinal spiking output in three types of mouse alpha RGCs (αRGCs). While sustained αRGC types have spike generators that are able to generate sustained trains of action potentials at high rates, the transient αRGC type fired shortest action potentials enabling them to fire high-frequency transient bursts. Computational modeling suggests that intrinsic response differences are not driven by dendritic morphology but by somatodendritc biophysics. After photoreceptor degeneration, the observed variability is preserved indicating stable physiology across the three αRGC types.

视网膜神经节细胞(RGC)是连接眼睛和大脑的神经元,通过平行通路传递外界的多种特征。虽然有大量文献介绍了这些通路是如何在视网膜网络中产生的,但人们对突触前输入转化为 RGC 尖峰输出的过程却知之甚少。在这项研究中,我们发现雌性和雄性小鼠的三种α RGC(αON持续性、αOFF持续性和αOFF瞬时性RGC)的尖峰发生器存在很大差异。它们内在尖峰反应的差异与不同类型 RGC 光反应的差异相吻合。持续型 RGC 的尖峰发生器能够以较高的速率产生持续的动作电位序列,而瞬时型 RGC 发射的动作电位最短,因此能够发射高频率的瞬时爆发。在感光器退化的晚期视网膜中也存在观察到的差异,这表明即使突触前电路长期恶化,RGC 反应的功能也能保持长期稳定。我们的研究结果表明,细胞的内在特性支持突触前视网膜计算,而且一旦建立,就与突触前视网膜计算无关。意义声明 长期以来,人们一直认为视网膜神经节细胞(RGC)的尖峰输出完全由视网膜网络的突触输入决定。我们的研究表明,细胞内在的尖峰发生器在不同的 RGC 群体中各不相同,因此突触后处理决定了三种类型的小鼠αRGC(αRGC)的视网膜尖峰输出。持续型αRGC的尖峰发生器能以较高的速率产生持续的动作电位序列,而瞬时型αRGC则能发射最短的动作电位,使它们能发射高频率的瞬时爆发。计算模型表明,内在反应差异不是由树突形态驱动的,而是由体细胞生物物理学驱动的。感光器退化后,观察到的变异性得以保留,这表明三种αRGC类型的生理机能稳定。
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引用次数: 0
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Journal of Neuroscience
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