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State-dependent modulation of positive and negative affective valences by a parabrachial nucleus-to-ventral tegmental area pathway in mice 小鼠臂旁核-腹侧被盖区通路对正、负情感价的状态依赖性调节
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-11-29 DOI: 10.3389/fncir.2023.1273322
Takashi Nagashima, Kaori Mikami, Suguru Tohyama, Ayumu Konno, Hirokazu Hirai, Ayako M. Watabe
Appropriately responding to various sensory signals in the environment is essential for animal survival. Accordingly, animal behaviors are closely related to external and internal states, which include the positive and negative emotional values of sensory signals triggered by environmental factors. While the lateral parabrachial nucleus (LPB) plays a key role in nociception and supports negative valences, it also transmits signals including positive valences. However, the downstream neuronal mechanisms of positive and negative valences have not been fully explored. In the present study, we investigated the ventral tegmental area (VTA) as a projection target for LPB neurons. Optogenetic activation of LPB-VTA terminals in male mice elicits positive reinforcement in an operant task and induces both avoidance and attraction in a place-conditioning task. Inhibition of glutamic acid decarboxylase (GAD) 65-expressing cells in the VTA promotes avoidance behavior induced by photoactivation of the LPB-VTA pathway. These findings indicate that the LPB-VTA pathway is one of the LPB outputs for the transmission of positive and negative valence signals, at least in part, with GABAergic modification in VTA.
对环境中的各种感官信号作出适当的反应对动物的生存至关重要。因此,动物行为与外部和内部状态密切相关,包括环境因素触发的感官信号的积极和消极情绪值。侧臂旁核(LPB)在伤害感觉中起着关键作用,支持负效,同时也传递包括正效在内的信号。然而,正负价的下游神经元机制尚未得到充分探索。在本研究中,我们研究了腹侧被盖区(VTA)作为LPB神经元的投射靶点。光遗传激活雄性小鼠LPB-VTA末端在操作性任务中引起正强化,在位置条件反射任务中引起回避和吸引。抑制VTA中表达谷氨酸脱羧酶(GAD) 65的细胞可促进LPB-VTA途径光激活诱导的回避行为。这些发现表明,LPB-VTA通路是LPB输出的正负价信号传递之一,至少在一定程度上,在VTA中存在gaba能修饰。
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引用次数: 0
Cross-species conservation in the regulation of parvalbumin by perineuronal nets 神经元周围网对副白蛋白的跨物种调控保护
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-11-29 DOI: 10.3389/fncir.2023.1297643
Angela S. Wang, Xinghaoyun Wan, Daria-Salina Storch, Vivian Y. Li, Gilles Cornez, Jacques Balthazart, J. Miguel Cisneros-Franco, Etienne de Villers-Sidani, Jon T. Sakata

Parvalbumin (PV) neurons play an integral role in regulating neural dynamics and plasticity. Therefore, understanding the factors that regulate PV expression is important for revealing modulators of brain function. While the contribution of PV neurons to neural processes has been studied in mammals, relatively little is known about PV function in non-mammalian species, and discerning similarities in the regulation of PV across species can provide insight into evolutionary conservation in the role of PV neurons. Here we investigated factors that affect the abundance of PV in PV neurons in sensory and motor circuits of songbirds and rodents. In particular, we examined the degree to which perineuronal nets (PNNs), extracellular matrices that preferentially surround PV neurons, modulate PV abundance as well as how the relationship between PV and PNN expression differs across brain areas and species and changes over development. We generally found that cortical PV neurons that are surrounded by PNNs (PV+PNN neurons) are more enriched with PV than PV neurons without PNNs (PV-PNN neurons) across both rodents and songbirds. Interestingly, the relationship between PV and PNN expression in the vocal portion of the basal ganglia of songbirds (Area X) differed from that in other areas, with PV+PNN neurons having lower PV expression compared to PV-PNN neurons. These relationships remained consistent across development in vocal motor circuits of the songbird brain. Finally, we discovered a causal contribution of PNNs to PV expression in songbirds because degradation of PNNs led to a diminution of PV expression in PV neurons. These findings reveal a conserved relationship between PV and PNN expression in sensory and motor cortices and across songbirds and rodents and suggest that PV neurons could modulate plasticity and neural dynamics in similar ways across songbirds and rodents.

副发光素(PV)神经元在调节神经动态和可塑性方面发挥着不可或缺的作用。因此,了解调控PV表达的因素对于揭示大脑功能的调节因子非常重要。虽然人们已经研究了哺乳动物中 PV 神经元对神经过程的贡献,但对非哺乳动物物种中 PV 功能的了解相对较少,而辨别不同物种中 PV 调控的相似性可以深入了解 PV 神经元作用的进化保护。在这里,我们研究了影响鸣禽和啮齿类动物感觉和运动回路中PV神经元中PV丰度的因素。特别是,我们研究了优先环绕 PV 神经元的细胞外基质--神经元周围网(PNN)--对 PV 丰度的调节程度,以及 PV 和 PNN 表达之间的关系在不同脑区和物种间的差异和发育过程中的变化。我们普遍发现,在啮齿动物和鸣禽中,被 PNNs 包围的皮层 PV 神经元(PV+PNN 神经元)比没有 PNNs 的 PV 神经元(PV-PNN 神经元)富含更多的 PV。有趣的是,鸣禽基底神经节发声部分(X 区)的 PV 和 PNN 表达关系与其他区域不同,PV+PNN 神经元的 PV 表达低于 PV-PNN 神经元。这些关系在鸣禽大脑发声运动回路的发育过程中保持一致。最后,我们发现 PNN 对鸣禽的 PV 表达有因果关系,因为 PNN 的退化会导致 PV 神经元中 PV 表达的减少。这些发现揭示了在鸣禽和啮齿类动物的感觉和运动皮层中,PV和PNN表达之间的保守关系,并表明在鸣禽和啮齿类动物中,PV神经元能以类似的方式调节可塑性和神经动力学。
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引用次数: 0
Do we all synch alike? Brain–body-environment interactions in ASD 我们都一样吗?ASD 的脑-体-环境相互作用
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-11-27 DOI: 10.3389/fncir.2023.1275896
Shlomit Beker, Sophie Molholm

Autism Spectrum Disorder (ASD) is characterized by rigidity of routines and restricted interests, and atypical social communication and interaction. Recent evidence for altered synchronization of neuro-oscillatory brain activity with regularities in the environment and of altered peripheral nervous system function in ASD present promising novel directions for studying pathophysiology and its relationship to ASD clinical phenotype. Human cognition and action are significantly influenced by physiological rhythmic processes that are generated by both the central nervous system (CNS) and the autonomic nervous system (ANS). Normally, perception occurs in a dynamic context, where brain oscillations and autonomic signals synchronize with external events to optimally receive temporally predictable rhythmic information, leading to improved performance. The recent findings on the time-sensitive coupling between the brain and the periphery in effective perception and successful social interactions in typically developed highlight studying the interactions within the brain–body-environment triad as a critical direction in the study of ASD. Here we offer a novel perspective of autism as a case where the temporal dynamics of brain–body-environment coupling is impaired. We present evidence from the literature to support the idea that in autism the nervous system fails to operate in an adaptive manner to synchronize with temporally predictable events in the environment to optimize perception and behavior. This framework could potentially lead to novel biomarkers of hallmark deficits in ASD such as cognitive rigidity and altered social interaction.

自闭症谱系障碍(ASD)的特点是生活常规僵化、兴趣受限、社会交流和互动不典型。最近有证据表明,自闭症患者大脑神经振荡活动与环境中规律性活动的同步性发生了改变,外周神经系统功能也发生了改变,这为研究病理生理学及其与自闭症临床表型的关系提供了新的方向。人类的认知和行动受到中枢神经系统(CNS)和自主神经系统(ANS)产生的生理节律过程的重大影响。正常情况下,感知发生在动态环境中,大脑振荡和自律神经信号与外部事件同步,以最佳方式接收时间上可预测的节律信息,从而提高表现。最近的研究发现,在典型发育患者的有效感知和成功社会交往中,大脑和外周之间的时间敏感耦合凸显了研究大脑-身体-环境三者之间的相互作用是研究自闭症的一个重要方向。在此,我们从一个新的角度将自闭症视为大脑-身体-环境耦合的时间动态受损的病例。我们从文献中提出证据,支持这样一种观点,即自闭症患者的神经系统无法以适应的方式与环境中时间上可预测的事件同步运行,从而优化感知和行为。这一框架有可能为自闭症的标志性缺陷(如认知僵化和社会交往改变)提供新的生物标志物。
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引用次数: 0
Editorial: Marine invertebrates: neurons, glia, and neurotransmitters. 社论:海洋无脊椎动物:神经元、神经胶质和神经递质。
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-11-14 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1327991
Tatiana N Olivares-Bañuelos, Arturo Ortega
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引用次数: 0
Acetylcholine facilitates localized synaptic potentiation and location specific feature binding 乙酰胆碱促进局部突触增强和位置特异性特征结合
3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-11-10 DOI: 10.3389/fncir.2023.1239096
Yihao Yang, Victoria Booth, Michal Zochowski
Forebrain acetylcholine (ACh) signaling has been shown to drive attention and learning. Recent experimental evidence of spatially and temporally constrained cholinergic signaling has sparked interest to investigate how it facilitates stimulus-induced learning. We use biophysical excitatory-inhibitory (E-I) multi-module neural network models to show that external stimuli and ACh signaling can mediate spatially constrained synaptic potentiation patterns. The effects of ACh on neural excitability are simulated by varying the conductance of a muscarinic receptor-regulated hyperpolarizing slow K+ current (m-current). Each network module consists of an E-I network with local excitatory connectivity and global inhibitory connectivity. The modules are interconnected with plastic excitatory synaptic connections, that change via a spike-timing-dependent plasticity (STDP) rule. Our results indicate that spatially constrained ACh release influences the information flow represented by network dynamics resulting in selective reorganization of inter-module interactions. Moreover the information flow depends on the level of synchrony in the network. For highly synchronous networks, the more excitable module leads firing in the less excitable one resulting in strengthening of the outgoing connections from the former and weakening of its incoming synapses. For networks with more noisy firing patterns, activity in high ACh regions is prone to induce feedback firing of synchronous volleys and thus strengthening of the incoming synapses to the more excitable region and weakening of outgoing synapses. Overall, these results suggest that spatially and directionally specific plasticity patterns, as are presumed necessary for feature binding, can be mediated by spatially constrained ACh release.
前脑乙酰胆碱(ACh)信号传导已被证明可以驱动注意力和学习。最近的实验证据表明,空间和时间限制胆碱能信号引发了研究它如何促进刺激诱导学习的兴趣。我们使用生物物理兴奋-抑制(E-I)多模块神经网络模型来证明外部刺激和乙酰胆碱信号可以介导空间受限的突触增强模式。通过改变毒蕈碱受体调节的超极化慢K+电流(m电流)的电导来模拟乙酰胆碱对神经兴奋性的影响。每个网络模块由一个具有局部兴奋性连接和全局抑制性连接的E-I网络组成。这些模块与可塑性兴奋性突触连接相互连接,这种连接通过峰值时间依赖的可塑性(STDP)规则变化。我们的研究结果表明,空间约束的ACh释放影响以网络动力学为代表的信息流,导致模块间相互作用的选择性重组。此外,信息流取决于网络中的同步水平。对于高度同步的神经网络,更容易兴奋的模块会引发不太容易兴奋的模块,导致前者的外向连接加强,而其传入突触减弱。对于具有更嘈杂的放电模式的网络,高乙酰氨基酚区域的活动容易诱导同步齐射的反馈放电,从而加强传入突触到更兴奋的区域,减弱传出突触。总的来说,这些结果表明空间和方向特异性的可塑性模式,作为特征结合的必要条件,可以通过空间约束的乙酰胆碱释放介导。
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引用次数: 0
Editorial: GABAergic circuits in health and disease. 编辑:gaba能回路在健康和疾病。
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-10-31 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1322193
Lisa Topolnik, Graziella Di Cristo, Elsa Rossignol
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引用次数: 0
The flow of axonal information among hippocampal sub-regions 2: patterned stimulation sharpens routing of information transmission 海马亚区之间的轴突信息流 2:模式化刺激使信息传输路线更加清晰
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-10-20 DOI: 10.3389/fncir.2023.1272925
Samuel Brandon Lassers, Yash S. Vakilna, William C. Tang, Gregory J. Brewer

The sub-regions of the hippocampal formation are essential for episodic learning and memory formation, yet the spike dynamics of each region contributing to this function are poorly understood, in part because of a lack of access to the inter-regional communicating axons. Here, we reconstructed hippocampal networks confined to four subcompartments in 2D cultures on a multi-electrode array that monitors individual communicating axons. In our novel device, somal, and axonal activity was measured simultaneously with the ability to ascertain the direction and speed of information transmission. Each sub-region and inter-regional axons had unique power-law spiking dynamics, indicating differences in computational functions, with abundant axonal feedback. After stimulation, spiking, and burst rates decreased in all sub-regions, spikes per burst generally decreased, intraburst spike rates increased, and burst duration decreased, which were specific for each sub-region. These changes in spiking dynamics post-stimulation were found to occupy a narrow range, consistent with the maintenance of the network at a critical state. Functional connections between the sub-region neurons and communicating axons in our device revealed homeostatic network routing strategies post-stimulation in which spontaneous feedback activity was selectively decreased and balanced by decreased feed-forward activity. Post-stimulation, the number of functional connections per array decreased, but the reliability of those connections increased. The networks maintained a balance in spiking and bursting dynamics in response to stimulation and sharpened network routing. These plastic characteristics of the network revealed the dynamic architecture of hippocampal computations in response to stimulation by selective routing on a spatiotemporal scale in single axons.

海马形成的各个亚区对情节性学习和记忆的形成至关重要,但人们对每个亚区促进这一功能的尖峰动态却知之甚少,部分原因是缺乏对区域间交流轴突的访问。在这里,我们通过多电极阵列监测单个交流轴突,在二维培养物中重建了局限于四个亚区的海马网络。在我们的新型装置中,体细胞和轴突活动被同时测量,并能确定信息传输的方向和速度。每个子区域和区域间轴突都有独特的幂律尖峰动态,表明计算功能存在差异,轴突反馈也很丰富。刺激后,所有亚区域的尖峰和爆发率均下降,每次爆发的尖峰数普遍减少,爆发内尖峰率增加,爆发持续时间缩短,这在每个亚区域都有特定的表现。研究发现,这些刺激后尖峰动态变化的范围很窄,与网络维持在临界状态一致。我们装置中的子区域神经元和通信轴突之间的功能连接显示了刺激后的平衡网络路由策略,其中自发反馈活动被选择性地减少,并被减少的前馈活动所平衡。刺激后,每个阵列的功能连接数量减少,但这些连接的可靠性却增加了。网络对刺激的反应保持了尖峰和爆发动态的平衡,并使网络路由更加清晰。网络的这些可塑性特征揭示了海马计算的动态结构,它通过单轴突在时空尺度上的选择性路由来响应刺激。
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引用次数: 0
GABAergic signaling in alcohol use disorder and withdrawal: pathological involvement and therapeutic potential. GABA能信号在酒精使用障碍和戒断中的作用:病理学意义和治疗潜力。
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-10-20 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1218737
Ravinder Naik Dharavath, Celeste Pina-Leblanc, Victor M Tang, Matthew E Sloan, Yuliya S Nikolova, Peter Pangarov, Anthony C Ruocco, Kevin Shield, Daphne Voineskos, Daniel M Blumberger, Isabelle Boileau, Nikki Bozinoff, Philip Gerretsen, Erica Vieira, Osnat C Melamed, Etienne Sibille, Lena C Quilty, Thomas D Prevot

Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs, and leads to approximately 3 million global deaths yearly. Alcohol use disorder (AUD) includes various drinking behavior patterns that lead to short-term or long-lasting effects on health. Ethanol, the main psychoactive molecule acting in alcoholic beverages, directly impacts the GABAergic system, contributing to GABAergic dysregulations that vary depending on the intensity and duration of alcohol consumption. A small number of interventions have been developed that target the GABAergic system, but there are promising future therapeutic avenues to explore. This review provides an overview of the impact of alcohol on the GABAergic system, the current interventions available for AUD that target the GABAergic system, and the novel interventions being explored that in the future could be included among first-line therapies for the treatment of AUD.

酒精是使用最广泛的物质之一。酒精使用占全球疾病负担的5.1%,大大增加了社会和经济成本,每年导致全球约300万人死亡。酒精使用障碍(AUD)包括对健康产生短期或长期影响的各种饮酒行为模式。乙醇是酒精饮料中的主要精神活性分子,它直接影响GABA能系统,导致GABA能失调,这种失调因饮酒强度和持续时间而异。已经开发了少量针对GABA能系统的干预措施,但未来还有很有希望的治疗途径可供探索。这篇综述概述了酒精对GABA能系统的影响,目前针对GABA能的AUD干预措施,以及正在探索的新干预措施,这些干预措施将来可能被纳入AUD治疗的一线疗法。
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引用次数: 0
Autogenous cerebral processes: an invitation to look at the brain from inside out. 自主大脑过程:一种从内到外观察大脑的邀请。
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-10-19 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1253609
Pedro E Maldonado, Miguel Concha-Miranda, Miriam Schwalm

While external stimulation can reliably trigger neuronal activity, cerebral processes can operate independently from the environment. In this study, we conceptualize autogenous cerebral processes (ACPs) as intrinsic operations of the brain that exist on multiple scales and can influence or shape stimulus responses, behavior, homeostasis, and the physiological state of an organism. We further propose that the field should consider exploring to what extent perception, arousal, behavior, or movement, as well as other cognitive functions previously investigated mainly regarding their stimulus-response dynamics, are ACP-driven.

虽然外部刺激可以可靠地触发神经元活动,但大脑过程可以独立于环境运行。在这项研究中,我们将自体脑过程(ACPs)概念化为大脑的内在操作,存在于多个尺度上,可以影响或塑造刺激反应、行为、稳态和生物体的生理状态。我们进一步提出,该领域应考虑探索感知、唤醒、行为或运动,以及之前主要针对其刺激反应动力学研究的其他认知功能,在多大程度上是ACP驱动的。
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引用次数: 0
Potential for host-symbiont communication via neurotransmitters and neuromodulators in an aneural animal, the marine sponge Amphimedon queenslandica. 通过神经递质和神经调节剂与宿主共生体交流的潜力在非整倍体动物,海洋海绵昆士兰两栖动物中。
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-09-29 eCollection Date: 2023-01-01 DOI: 10.3389/fncir.2023.1250694
Xueyan Xiang, Arturo A Vilar Gomez, Simone P Blomberg, Huifang Yuan, Bernard M Degnan, Sandie M Degnan

Interkingdom signalling within a holobiont allows host and symbionts to communicate and to regulate each other's physiological and developmental states. Here we show that a suite of signalling molecules that function as neurotransmitters and neuromodulators in most animals with nervous systems, specifically dopamine and trace amines, are produced exclusively by the bacterial symbionts of the demosponge Amphimedon queenslandica. Although sponges do not possess a nervous system, A. queenslandica expresses rhodopsin class G-protein-coupled receptors that are structurally similar to dopamine and trace amine receptors. When sponge larvae, which express these receptors, are exposed to agonists and antagonists of bilaterian dopamine and trace amine receptors, we observe marked changes in larval phototactic swimming behaviour, consistent with the sponge being competent to recognise and respond to symbiont-derived trace amine signals. These results indicate that monoamines synthesised by bacterial symbionts may be able to influence the physiology of the host sponge.

全生物体内的界间信号允许宿主和共生体交流并调节彼此的生理和发育状态。在这里,我们发现,在大多数有神经系统的动物中,一系列信号分子,特别是多巴胺和微量胺,作为神经递质和神经调节剂,完全由昆斯兰双足虫的细菌共生体产生。尽管海绵不具有神经系统,但昆士兰a.queenslandica表达与多巴胺和微量胺受体结构相似的视紫红质类G蛋白偶联受体。当表达这些受体的海绵幼虫暴露于双侧多巴胺和微量胺受体的激动剂和拮抗剂时,我们观察到幼虫的趋光游泳行为发生了显著变化,这与海绵能够识别和响应共生体衍生的微量胺信号相一致。这些结果表明,由细菌共生体合成的单胺可能能够影响宿主海绵的生理学。
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引用次数: 0
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Frontiers in Neural Circuits
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