BACKGROUND & AIMS: :In the nervous system, many intracellular responses to elevated calcium are mediated by CaM kinases (CaMKs), a family of protein kinases whose activities are initially modulated by binding Ca(2+)/calmodulin and subsequently by protein phosphorylation. One member of this family, CaMKII, is well-established for its effects on modulating synaptic plasticity and learning and memory. However, recent studies indicate that some actions on neuronal development and function attributed to CaMKII may instead or in addition be mediated by other members of the CaMK cascade, such as CaMKK, CaMKI, and CaMKIV. This review summarizes key neuronal functions of the CaMK cascade in signal transduction, gene transcription, synaptic development and plasticity, and behavior. The technical challenges of mapping cellular protein kinase signaling pathways are also discussed.

背景与目标： : 在神经系统中，许多细胞内对钙升高的反应是由CaM激酶 (CaMKs) 介导的，CaM激酶是一种蛋白质激酶家族，其活性最初通过结合Ca(2)/钙调蛋白以及随后通过蛋白质磷酸化来调节。这个家族的一个成员CaMKII因其对调节突触可塑性以及学习和记忆的作用而广为人知。然而，最近的研究表明，CaMKII对神经元发育和功能的某些作用可能会被CaMK级联的其他成员 (例如CaMKK，CaMKI和CaMKIV) 介导。这篇综述总结了CaMK级联在信号转导，基因转录，突触发育和可塑性以及行为中的关键神经元功能。还讨论了定位细胞蛋白激酶信号通路的技术挑战。

BACKGROUND & AIMS: :Microglia populate the early developing brain and mediate pruning of the central synapses. Yet, little is known on their functional significance in shaping the developing cortical circuits. We hypothesize that the developing cortical circuits require microglia for proper circuit maturation and connectivity, and as such, ablation of microglia during the cortical critical period may result in a long-lasting circuit abnormality. We administered PLX3397, a colony-stimulating factor 1 receptor inhibitor, to mice starting at postnatal day 14 and through P28, which depletes >75% of microglia in the visual cortex (VC). This treatment largely covers the critical period (P19-32) of VC maturation and plasticity. Patch clamp recording in VC layer 2/3 (L2/3) and L5 neurons revealed increased mEPSC frequency and reduced amplitude, and decreased AMPA/NMDA current ratio, indicative of altered synapse maturation. Increased spine density was observed in these neurons, potentially reflecting impaired synapse pruning. In addition, VC intracortical circuit functional connectivity, assessed by laser scanning photostimulation combined with glutamate uncaging, was dramatically altered. Using two photon longitudinal dendritic spine imaging, we confirmed that spine elimination/pruning was diminished during VC critical period when microglia were depleted. Reduced spine pruning thus may account for increased spine density and disrupted connectivity of VC circuits. Lastly, using single-unit recording combined with monocular deprivation, we found that ocular dominance plasticity in the VC was obliterated during the critical period as a result of microglia depletion. These data establish a critical role of microglia in developmental cortical synapse pruning, maturation, functional connectivity, and critical period plasticity.

背景与目标： : 小胶质细胞填充早期发育的大脑，并介导中枢突触的修剪。然而，人们对它们在形成发育中的皮质回路中的功能意义知之甚少。我们假设正在发育的皮质回路需要小胶质细胞才能进行适当的回路成熟和连通性，因此，在皮质关键时期消融小胶质细胞可能会导致长期的回路异常。我们从出生后第14天至P28对小鼠施用PLX3397，一种集落刺激因子1受体抑制剂，其消耗视皮层 (VC) 中> 75% 的小胶质细胞。这种处理在很大程度上涵盖了VC成熟和可塑性的关键时期 (P19-32)。VC层2/3 (L2/3) 和L5神经元中的膜片钳记录显示mEPSC频率增加，振幅降低，AMPA/NMDA电流比降低，表明突触成熟改变。在这些神经元中观察到脊柱密度增加，可能反映出突触修剪受损。此外，通过激光扫描光刺激结合谷氨酸缠结评估的VC皮质内电路功能连通性发生了显着变化。使用两个光子纵向树突状脊柱成像，我们证实了在小胶质细胞耗尽的VC关键时期，脊柱消除/修剪减少了。因此，减少脊柱修剪可能会导致脊柱密度增加和VC电路的连通性中断。最后，使用单单元记录与单眼剥夺相结合，我们发现，由于小胶质细胞耗竭，VC中的眼优势可塑性在关键时期被消除。这些数据确立了小胶质细胞在发育性皮层突触修剪，成熟，功能连接和关键期可塑性中的关键作用。

BACKGROUND & AIMS: :Robustness against environmental fluctuations within an adaptive state should preclude exploration of new adaptive states when the environment changes. Here, we study transitions between adaptive associations of feather structure and carotenoid uptake to understand how robustness and evolvability can be reconciled. We show that feather modifications induced by unfamiliar carotenoids during a range expansion are repeatedly converted into precise coadaptations of feather development and carotenoid accommodation as populations persist in a region. We find that this conversion is underlain by a uniform and coordinated increase in the sensitivity of feather development to local carotenoid uptake, indicative of cooption and modification of the homeostatic mechanism that buffers feather growth in the evolution of new adaptations. Stress-buffering mechanisms are well placed to alternate between robustness and evolvability and we suggest that this is particularly evident in adaptations that require close integration between widely fluctuating external inputs and intricate internal structures.

背景与目标： : 适应状态内对环境波动的鲁棒性应排除在环境变化时探索新的适应状态。在这里，我们研究了羽毛结构与类胡萝卜素摄取之间的适应性关联之间的过渡，以了解如何协调鲁棒性和可进化性。我们表明，随着种群在一个地区的持续存在，在范围扩展过程中由不熟悉的类胡萝卜素引起的羽毛修饰会反复转化为羽毛发育和类胡萝卜素适应的精确协适应。我们发现，这种转化是通过羽毛发育对局部类胡萝卜素摄取的敏感性的均匀和协调增加而实现的，这表明了在新的适应进化过程中缓冲羽毛生长的稳态机制的共同选择和修饰。应力缓冲机制可以在鲁棒性和可进化性之间进行交替，我们建议在需要广泛波动的外部输入和复杂的内部结构之间紧密结合的适应中尤为明显。

BACKGROUND & AIMS: :If an ancestral stem group repeatedly colonizes similar environments, developmental plasticity specific to that group should consistently give rise to similar phenotypes. Parallel selection on those similar phenotypes could lead to the repeated evolution of characteristic ecotypes, a property common to many adaptive radiations. A key prediction of this "flexible stem" model of adaptive radiation is that patterns of phenotypic divergence in derived groups should mirror patterns of developmental plasticity in their common ancestor. The threespine stickleback radiation provides an excellent opportunity to test this prediction because the marine form is representative of the ancestral stem group, which has repeatedly given rise to several characteristic ecotypes. We examined plasticity of several aspects of shape and trophic morphology in response to diets characteristic of either the derived benthic ecotype or the limnetic ecotype. When marine fish were reared on alternative diets, plasticity of head and mouth shape paralleled phenotypic divergence between the derived ecotypes, supporting the flexible stem model. Benthic and limnetic fish exhibited patterns of plasticity similar to those of the marine population; however, some differences in population means were present, as well as subtle differences in shape plasticity in the benthic population, indicating a role for genetic accommodation in this system.

背景与目标： : 如果祖先的茎群反复定居在相似的环境中，则该群体特有的发育可塑性应始终产生相似的表型。对这些相似表型的平行选择可能导致特征性生态型的重复进化，这是许多适应性辐射的共同特征。这种适应性辐射的 “柔性茎” 模型的关键预测是，衍生群体的表型差异模式应反映其共同祖先的发育可塑性模式。Threeshine stickleback辐射为测试此预测提供了绝佳的机会，因为海洋形式代表了祖先茎群，该祖先茎群反复产生了几种特征性的生态型。我们研究了形状和营养形态几个方面的可塑性，以响应衍生的底栖生态型或边缘生态型的饮食特征。当以替代饮食饲养海水鱼时，头部和嘴巴形状的可塑性与衍生生态型之间的表型差异平行，支持柔性茎模型。底栖鱼类和limnetic鱼类表现出与海洋种群相似的可塑性模式; 但是，在底栖动物种群中存在种群方式上的一些差异，以及形状可塑性上的细微差异，表明该系统中的遗传调节作用。

BACKGROUND & AIMS: :The kinesin I family of motor proteins are crucial for axonal transport, but their roles in dendritic transport and postsynaptic function are not well-defined. Gene duplication and subsequent diversification give rise to three homologous kinesin I proteins (KIF5A, KIF5B and KIF5C) in vertebrates, but it is not clear whether and how they exhibit functional specificity. Here we show that knockdown of KIF5A or KIF5B differentially affects excitatory synapses and dendritic transport in hippocampal neurons. The functional specificities of the two kinesins are determined by their diverse carboxyl-termini, where arginine methylation occurs in KIF5B and regulates its function. KIF5B conditional knockout mice exhibit deficits in dendritic spine morphogenesis, synaptic plasticity and memory formation. Our findings provide insights into how expansion of the kinesin I family during evolution leads to diversification and specialization of motor proteins in regulating postsynaptic function. :Transporting molecules within a cell becomes a daunting task when the cell is a neuron, with fibers called axons and dendrites that can stretch as long as a meter. Neurons use many different molecules to send messages across the body and store memories in the brain. If the right molecules cannot be delivered along the length of nerve cells, connections to neighboring neurons may decay, which may impair learning and memory. Motor proteins are responsible for transporting molecules within cells. Kinesins are a type of motor protein that typically transports materials from the body of a neuron to the cell’s periphery, including the dendrites, which is where a neuron receives messages from other nerve cells. Each cell has up to 45 different kinesin motors, but it is not known whether each one performs a distinct task or if they have overlapping roles. Now, Zhao, Fok et al. have studied two similar kinesins, called KIF5A and KIF5B, in rodent neurons to determine their roles. First, it was shown that both proteins were found at dendritic spines, which are small outgrowths on dendrites where contact with other cells occurs. Next, KIF5A and KIF5B were depleted, one at a time, from neurons extracted from a brain region called the hippocampus. Removing KIF5B interfered with the formation of dendritic spines, but removing KIF5A did not have an effect. Dendritic spines are essential for learning and memory, so several behavioral tests were conducted on mice that had been genetically modified to express less KIF5B in the forebrain. These tests revealed that the mice performed poorly in tasks that tested their memory recall. This work opens a new area of research studying the specific roles of different kinesin motor proteins in nerve cells. This could have important implications because certain kinesin motor proteins such as KIF5A are known to be defective in some inherited neurodegenerative diseases.

背景与目标：

BACKGROUND & AIMS: :Dendritic cells (DCs) are professional antigen-presenting cells that have an extraordinary capacity to stimulate naïve T cells and initiate primary immune responses. Here we review progress in understanding the additional functions of DCs in regulating the types of T cell-mediated immune responses and innate immunity to microbes. In addition, evidence for the existence of myeloid and lymphoid DC lineages and their different functions are summarized. We propose that the diverse functions of DCs in immune regulation are dictated by the instructions they received during innate immune responses to different pathogens and from their evolutionary lineage heritage.

背景与目标： : 树突状细胞 (dc) 是专业的抗原呈递细胞，具有刺激幼稚T细胞和启动初级免疫反应的非凡能力。在这里，我们回顾了了解dc在调节T细胞介导的免疫应答类型和对微生物的先天免疫中的附加功能方面的进展。此外，总结了骨髓和淋巴DC谱系的存在及其不同功能的证据。我们建议dc在免疫调节中的不同功能是由它们在对不同病原体及其进化谱系遗传的先天免疫反应中收到的指令决定的。

BACKGROUND & AIMS: :Protease-mediated signaling is an important modulator of the nervous system. However, identifying the specific signaling substrates of such proteases is limited by the rapidity with which intermediate substrate forms are cleaved and released. Here, a screening method to detect noncleaved enzyme-bound forms was developed and used to identify a novel neuropsin/neuregulin-1 (NRG-1) proteolytic signaling system, which is specifically localized in the microdomain of synaptic cleft, in the mouse hippocampus. The extracellular protease, neuropsin, cleaved mature NRG-1 (comprising the extracellular domain of the NRG-1) at three newly identified sites to remove the heparin-binding domain of NRG-1. This released the ligand moiety from the matrix-glycosaminoglycan pool and enabled it to trigger the phosphorylation of NRG-1 receptor, p185 (ErbB4). Proteolysis of mature NRG-1 by neuropsin led to colocalization of the processed NRG-1 with ErbB4 in parvalbumin-positive hippocampal interneurons and consequent phosphorylation of tyrosine residues of proteins in the cells. Moreover, neuropsin knock-out mice exhibited impairments in Schaffer collateral early phase long-term potentiation, and application of the recombinant NRG-1 lacking heparin-binding activity reversed the effects through the activation of ErbB4 and GABA(A) receptors. Thus, ErbB4 signaling induced by neuropsin-dependent processing of NRG-1 contributes to the modulation of synaptic plasticity via regulation of GABAergic transmission. This signaling system may be involved in human cognition and mental disorders, such as schizophrenia and bipolar disorder, by its dysfunction.

背景与目标： 蛋白酶介导的信号传导是神经系统的重要调节剂。然而，鉴定这种蛋白酶的特定信号传导底物受到中间底物形式被裂解和释放的速度的限制。在这里，开发了一种检测未裂解酶结合形式的筛选方法，并将其用于鉴定新的神经蛋白酶/neuregulin-1 (NRG-1) 蛋白水解信号系统，该系统特别位于小鼠海马的突触间隙的微域中。细胞外蛋白酶神经蛋白酶在三个新鉴定的位点切割成熟NRG-1 (包括NRG-1的细胞外结构域) 以去除NRG-1的肝素结合结构域。这从基质-糖胺聚糖库释放配体部分，并使其能够触发NRG-1受体p185 (ErbB4) 的磷酸化。神经蛋白酶对成熟NRG-1的蛋白水解导致加工NRG-1与ErbB4在小白蛋白阳性海马中间神经元中的共定位，并导致细胞中蛋白质的酪氨酸残基磷酸化。此外，神经蛋白酶敲除小鼠在Schaffer附带的早期长期增强中表现出损伤，并且缺乏肝素结合活性的重组NRG-1的应用通过激活ErbB4和GABA(A) 受体逆转了作用。因此，由神经蛋白酶依赖性NRG-1处理诱导的ErbB4信号通过调节gaba能传递而有助于调节突触可塑性。该信号系统可能因其功能障碍而参与人类认知和精神障碍，例如精神分裂症和躁郁症。

BACKGROUND & AIMS: :Despite inactivating APC mutations, colorectal cancers express the WNT-effector protein β-catenin in a heterogeneous pattern, with strong nuclear expression confined to a fraction of tumor cells, often only at the tumor's leading edge. WNT-reporter constructs allow separation of these tumor cells with highest WNT/β-Catenin activity, which also express high levels of several putative cancer stem cell antigens. Unexpectedly however, these cells do not show exclusive tumorigenicity in xenograft experiments, thus questioning their general stemness phenotype. Instead, there appears to be significant plasticity between both tumor cells with high and low WNT/β-Catenin activity because both cell types can form tumors which again show mixed populations. Furthermore, WNT/β-Catenin activity in colon cancer cells can be modulated by MAPK signaling thus revealing a means of how other signaling pathways contribute to WNT signaling plasticity in colon cancer.

背景与目标： : 尽管失活APC突变，大肠癌仍以异质模式表达WNT效应蛋白 β-catenin，其强核表达仅限于一小部分肿瘤细胞，通常仅在肿瘤的前沿。WNT-报告分子构建体允许分离具有最高WNT/β-Catenin活性的这些肿瘤细胞，这些细胞也表达高水平的几种假定的癌症干细胞抗原。然而，出乎意料的是，这些细胞在异种移植实验中没有显示出排他性的致瘤性，因此质疑它们的一般干性表型。相反，两种具有高WNT/β-Catenin活性和低的肿瘤细胞之间似乎都具有显着的可塑性，因为两种细胞类型都可以形成肿瘤，再次显示出混合种群。此外，结肠癌细胞中的WNT/β-Catenin活性可以通过MAPK信号调节，从而揭示了其他信号通路如何促进结肠癌中WNT信号可塑性的手段。

BACKGROUND & AIMS: :Pain modulatory circuitry in the brainstem exhibits considerable synaptic plasticity. The increased peripheral neuronal barrage after injury activates spinal projection neurons that then activate multiple chemical mediators including glutamatergic neurons at the brainstem level, leading to an increased synaptic strength and facilitatory output. It is not surprising that a well-established regulator of synaptic plasticity, brain-derived neurotrophic factor (BDNF), contributes to the mechanisms of descending pain facilitation. After tissue injury, BDNF and TrkB signaling in the brainstem circuitry is rapidly activated. Through the intracellular signaling cascade that involves phospholipase C, inositol trisphosphate, protein kinase C, and nonreceptor protein tyrosine kinases; N-methyl-D-aspartate (NMDA) receptors are phosphorylated, descending facilitatory drive is initiated, and behavioral hyperalgesia follows. The synaptic plasticity observed in the pain pathways shares much similarity with more extensively studied forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD), which typically express NMDA receptor dependency and regulation by trophic factors. However, LTP and LTD are experimental phenomena whose relationship to functional states of learning and memory has been difficult to prove. Although mechanisms of synaptic plasticity in pain pathways have typically not been related to LTP and LTD, pain pathways have an advantage as a model system for synaptic modifications as there are many well-established models of persistent pain with clear measures of the behavioral phenotype. Further studies will elucidate cellular and molecular mechanisms of pain sensitization and further our understanding of principles of central nervous system plasticity and responsiveness to environmental challenge.

背景与目标： : 脑干中的疼痛调节电路表现出相当大的突触可塑性。损伤后增加的外周神经元弹幕会激活脊髓投射神经元，然后在脑干水平激活包括谷氨酸能神经元在内的多种化学介质，从而导致突触强度和促进输出增加。众所周知，突触可塑性的良好调节剂脑源性神经营养因子 (BDNF) 有助于促进疼痛下降的机制。组织损伤后，脑干回路中的BDNF和TrkB信号被迅速激活。通过涉及磷脂酶C，肌醇三磷酸，蛋白激酶C和非受体蛋白酪氨酸激酶的细胞内信号级联; N-甲基-D-天冬氨酸 (NMDA) 受体被磷酸化，开始下行促进驱动，随后出现行为痛觉过敏。在疼痛途径中观察到的突触可塑性与更广泛研究的突触可塑性形式 (例如长期增强 (LTP) 和长期抑郁 (LTD)) 具有许多相似性，它们通常表示NMDA受体依赖性和营养因子的调节。然而，LTP和LTD是实验现象，其与学习和记忆功能状态的关系一直难以证明。尽管疼痛途径中突触可塑性的机制通常与LTP和LTD无关，但疼痛途径作为突触修饰的模型系统具有优势，因为有许多公认的持续性疼痛模型具有明确的行为表型度量。进一步的研究将阐明疼痛致敏的细胞和分子机制，并进一步了解中枢神经系统可塑性和对环境挑战的反应性原理。

BACKGROUND & AIMS: :Xylene and its derivatives are known to be neurotoxic to the central nervous system of animals. Our previous work has shown that para-xylene (PX) can cause an increase in apoptotic cells and abnormal avoidance behavior in Xenopus laevis. However, the mechanism underlying the impact of PX on neuronal structural and functional plasticity is less clear. Here, we examined the effects of PX on neuronal development and plasticity in the developing optic tectum. We found that HuC/D-positive neurons were more vulnerable than SOX2-positive progenitor cells or BLBP-positive radial glial cells after exposure to PX at 1 mM for 48 h. The further measurement of postsynaptic receptors and synaptic vesicle proteins showed that the expression levels of GluA1 and GluA2, but not Rab3a and SNAP25, were significantly decreased in the tectal brain. In vivo time-lapse images and electrophysiological recordings showed that PX exposure resulted in significant deficits in neuronal structure, particularly in the total dendritic branch length (TDBL), and visual stimulation-induced excitatory compound synaptic currents (eCSCs) without altering neurotransmitter release probability. Strikingly, coexposure to d-glucuronolactone (GA) and PX rescued the structural and functional deficits caused by PX exposure alone. Furthermore, we found that visual experience-induced structural, functional and behavioral plasticity was blocked by PX exposure, which was also rescued by the simultaneous administration of GA and PX . Thus, our findings indicate that PX is neurotoxic to brain development and plasticity and that GA may be considered a promising candidate to treat PX-induced defects in neural circuits.

背景与目标： : 二甲苯及其衍生物已知对动物的中枢神经系统具有神经毒性。我们先前的工作表明，对二甲苯 (PX) 可以引起非洲爪蟾凋亡细胞的增加和异常的回避行为。然而，PX对神经元结构和功能可塑性影响的潜在机制尚不清楚。在这里，我们研究了PX对发育中的视神经的发育和可塑性的影响。我们发现，在暴露于1毫米的PX 48小时后，HuC/D阳性神经元比SOX2-positive祖细胞或BLBP阳性的放射状神经胶质细胞更脆弱。对突触后受体和突触小泡蛋白的进一步测量表明，在大脑皮层中GluA1和GluA2的表达水平显着降低，而Rab3a和SNAP25的表达水平却没有降低。体内延时图像和电生理记录显示，PX暴露导致神经元结构显着缺陷，尤其是总树突分支长度 (TDBL) 和视觉刺激诱导的兴奋性复合突触电流 (eCSCs)，而不改变神经递质释放概率。令人惊讶的是，共同暴露于d-葡萄糖醛酸内酯 (GA) 和PX可挽救仅由PX暴露引起的结构和功能缺陷。此外，我们发现视觉体验诱导的结构，功能和行为可塑性被PX暴露所阻断，而同时施用GA和PX也可以挽救。因此，我们的发现表明PX对大脑发育和可塑性具有神经毒性，并且GA可能被认为是治疗PX诱导的神经回路缺陷的有希望的候选者。

BACKGROUND & AIMS: :In the last decade, many studies confirmed the benefits of mental practice with motor imagery. In this review we first aimed to compile data issued from fundamental and clinical investigations and to provide the key-components for the optimization of motor imagery strategy. We focused on transcranial magnetic stimulation studies, supported by brain imaging research, that sustain the current hypothesis of a functional link between cortical reorganization and behavioral improvement. As perspectives, we suggest a model of neural adaptation following mental practice, in which synapse conductivity and inhibitory mechanisms at the spinal level may also play an important role.

背景与目标： : 在过去的十年中，许多研究证实了通过运动意象进行心理练习的好处。在这篇综述中，我们首先旨在收集基础和临床研究发布的数据，并为优化运动图像策略提供关键组件。我们专注于在脑成像研究的支持下进行的经颅磁刺激研究，这些研究维持了皮质重组与行为改善之间功能联系的当前假设。作为观点，我们提出了一种心理实践后的神经适应模型，其中脊髓水平的突触传导性和抑制机制也可能发挥重要作用。

BACKGROUND & AIMS: :Beige adipocytes are defined as Ucp1+, multilocular adipocytes within white adipose tissue (WAT) that are capable of thermogenesis, the process of heat generation. In both mouse models and humans, the increase of beige adipocyte population, also called WAT browning, is associated with certain metabolic benefits, such as reduced obesity and increased insulin sensitivity. In this review, we summarize the current knowledge regarding WAT browning, with a special focus on the beige adipocyte plasticity, collectively referring to a bidirectional transition between thermogenic active and latent states in response to environmental changes. We further exploit the utility of a unique beige adipocyte ablation system to interrogate anti-obesity effect of beige adipocytes in vivo.

背景与目标： : 米色脂肪细胞定义为Ucp1 +，白色脂肪组织 (WAT) 内的多房脂肪细胞，能够产热，产热过程。在小鼠模型和人类中，米色脂肪细胞数量的增加 (也称为WAT褐变) 与某些代谢益处有关，例如肥胖减少和胰岛素敏感性增加。在这篇综述中，我们总结了有关WAT褐变的最新知识，特别关注米色脂肪细胞的可塑性，统称为响应环境变化而在产热活性和潜伏态之间的双向过渡。我们进一步利用独特的米色脂肪细胞消融系统的实用性来询问体内米色脂肪细胞的抗肥胖作用。

BACKGROUND & AIMS: :Ocular dominance plasticity is a widely studied model of experience-dependent cortical plasticity. It has been shown that potentiation of open eye responses resulting from monocular deprivation relies on a homeostatic response to loss of input from the closed eye, but the mechanisms by which this occurs are not fully understood. The role of GluA1 in the homeostatic component of ocular dominance (OD) plasticity has not so far been tested. In this study, we tested the idea that the GluA1 subunit of the AMPA receptor is necessary for open eye potentiation. We found that open eye potentiation did not occur in GluA1 knock-out (GluA1(-/-)) mice but did occur in wild-type littermates when monocular deprivation was imposed during the critical period. We also found that depression of the closed eye response that normally occurs in the monocular as well as binocular zone is delayed, but only in the monocular zone in GluA1(-/-) mice and only in a background strain we have previously shown lacks synaptic scaling (C57BL/6OlaHsd). In adult mice, we found that OD plasticity and facilitation of OD plasticity by prior monocular experience were both present in GluA1(-/-) mice, suggesting that the GluA1-dependent mechanisms only operate during the critical period.

背景与目标： : 眼优势可塑性是一种广泛研究的经验依赖性皮层可塑性模型。已经表明，单眼剥夺引起的睁眼反应的增强依赖于对闭眼输入损失的稳态反应，但是这种发生的机制尚不完全清楚。到目前为止，尚未测试GluA1在眼优势 (OD) 可塑性的稳态成分中的作用。在这项研究中，我们测试了AMPA受体的GluA1亚基对于睁眼增强是必需的想法。我们发现，在关键时期施加单眼剥夺时，GluA1敲除 (GluA1(-/-)) 小鼠不会发生睁眼增强作用，但在野生型同窝中确实发生。我们还发现，通常在单眼和双眼区域中发生的闭眼反应的抑制被延迟，但仅在GluA1(-/-) 小鼠的单眼区域中，并且仅在我们先前显示的背景菌株中缺乏突触缩放 (C57BL/6OlaHsd)。在成年小鼠中，我们发现GluA1(-/-) 小鼠中都存在OD可塑性和先前单眼经验对OD可塑性的促进作用，这表明GluA1-dependent机制仅在关键时期起作用。

BACKGROUND & AIMS: :There has been an explosion of new information on the neurobiology of dendritic spines in synaptic signaling, integration, and plasticity. Novel imaging and analytical techniques have provided important new insights into dendritic spine structure and function. Results are accumulating across many disciplines, and a step toward consolidating some of this work has resulted in Dendritic Spines of the Hippocampus. Leaders in the field provide a discussion at the level of advanced under-graduates, with sufficient detail to be a contemporary resource for research scientists. Critical reviews are presented on topics ranging from spine structure, formation, and maintenance, to molecular composition, plasticity, and the role of spines in learning and memory. Dendritic Spines of the Hippocampus provides a timely discussion of our current understanding of form and function at these excitatory synapses. We asked authors to include areas of controversy in their papers so as to distinguish results that are generally agreed upon from those where multiple interpretations are possible. We thank the contributors for their insights and thoughtful discussions. In this paper we provide background on the structure, composition, function, development, plasticity, and pathology of hippocampal dendritic spines. In addition, we highlight where each of these subjects will be elaborated upon in subsequent papers of this special issue of Hippocampus.

背景与目标： : 关于突触信号，整合和可塑性中树突棘的神经生物学的新信息激增。新颖的成像和分析技术为树突状脊柱的结构和功能提供了重要的新见解。结果在许多学科中都在积累，并且朝着巩固某些工作的方向迈出了一步，导致了海马的树突棘。该领域的领导者在高级本科毕业生的水平上进行了讨论，并提供了足够的细节，可以成为研究科学家的当代资源。从脊柱的结构，形成和维护到分子组成，可塑性以及脊柱在学习和记忆中的作用等主题都提出了重要的评论。海马的树突棘及时讨论了我们目前对这些兴奋性突触的形式和功能的理解。我们要求作者在论文中包括有争议的领域，以便将普遍同意的结果与可能进行多种解释的结果区分开。我们感谢贡献者的见解和深思熟虑的讨论。在本文中，我们提供了有关海马树突棘的结构，组成，功能，发育，可塑性和病理的背景。此外，我们将在本《海马》特刊的后续论文中重点介绍这些主题中的每个主题。

BACKGROUND & AIMS: :Despite the ubiquity of sleep across phylogeny, its function remains elusive. In this review, we consider one compelling candidate: brain plasticity associated with memory processing. Focusing largely on hippocampus-dependent memory in rodents and humans, we describe molecular, cellular, network, whole-brain and behavioral evidence establishing a role for sleep both in preparation for initial memory encoding, and in the subsequent offline consolidation of memory. Sleep and sleep deprivation bidirectionally alter molecular signaling pathways that regulate synaptic strength and control plasticity-related gene transcription and protein translation. At the cellular level, sleep deprivation impairs cellular excitability necessary for inducing synaptic potentiation and accelerates the decay of long-lasting forms of synaptic plasticity. In contrast, rapid eye movement (REM) and non-rapid eye movement (NREM) sleep enhance previously induced synaptic potentiation, although synaptic de-potentiation during sleep has also been observed. Beyond single cell dynamics, large-scale cell ensembles express coordinated replay of prior learning-related firing patterns during subsequent NREM sleep. At the whole-brain level, somewhat analogous learning-associated hippocampal (re)activation during NREM sleep has been reported in humans. Moreover, the same cortical NREM oscillations associated with replay in rodents also promote human hippocampal memory consolidation, and this process can be manipulated using exogenous reactivation cues during sleep. Mirroring molecular findings in rodents, specific NREM sleep oscillations before encoding refresh human hippocampal learning capacity, while deprivation of sleep conversely impairs subsequent hippocampal activity and associated encoding. Together, these cross-descriptive level findings demonstrate that the unique neurobiology of sleep exerts powerful effects on molecular, cellular and network mechanisms of plasticity that govern both initial learning and subsequent long-term memory consolidation.

背景与目标： : 尽管在系统发育中普遍存在睡眠，但其功能仍然难以捉摸。在这篇评论中，我们考虑了一个令人信服的候选者: 与记忆处理相关的大脑可塑性。我们主要关注啮齿动物和人类的海马依赖性记忆，我们描述了分子，细胞，网络，全脑和行为证据，这些证据确立了睡眠在准备初始记忆编码以及随后的离线记忆巩固中的作用。睡眠和睡眠剥夺双向改变调节突触强度和控制可塑性相关基因转录和蛋白质翻译的分子信号通路。在细胞水平上，睡眠剥夺会损害诱导突触增强所必需的细胞兴奋性，并加速持久形式的突触可塑性的衰减。相反，快速眼动 (REM) 和非快速眼动 (NREM) 睡眠增强了先前诱导的突触增强，尽管还观察到睡眠期间的突触去势。除了单细胞动力学之外，大规模细胞集合在随后的NREM睡眠中表达了先前与学习相关的触发模式的协调重播。在全脑水平上，已经报道了人类在NREM睡眠期间类似的学习相关海马 (re) 激活。此外，与啮齿动物重放相关的相同皮质NREM振荡也促进了人类海马记忆的巩固，这个过程可以在睡眠中使用外源性的再激活线索来操纵。反映啮齿动物的分子发现，在编码刷新人类海马学习能力之前的特定NREM睡眠振荡，而睡眠的剥夺反过来会损害随后的海马活动和相关的编码。一起，这些交叉描述性水平的发现表明，睡眠的独特神经生物学对分子，细胞和网络可塑性机制产生了强大的影响，这些机制控制着初始学习和随后的长期记忆巩固。