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https://www.readbyqxmd.com/read/28447990/imaging-neurons-within-thick-brain-sections-using-the-golgi-cox-method
#1
Emma L Louth, Charles D Sutton, Ari L Mendell, Neil J MacLusky, Craig D C Bailey
The Golgi-Cox method of neuron staining has been employed for more than two hundred years to advance our understanding of neuron morphology within histological brain samples. While it is preferable from a practical perspective to prepare brain sections at the greatest thickness possible, in order to increase the probability of identifying stained neurons that are fully contained within single sections, this approach is limited from a technical perspective by the working distance of high-magnification microscope objectives...
April 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28445462/cell-diversity-and-network-dynamics-in-photosensitive-human-brain-organoids
#2
Giorgia Quadrato, Tuan Nguyen, Evan Z Macosko, John L Sherwood, Sung Min Yang, Daniel R Berger, Natalie Maria, Jorg Scholvin, Melissa Goldman, Justin P Kinney, Edward S Boyden, Jeff W Lichtman, Ziv M Williams, Steven A McCarroll, Paola Arlotta
In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28442576/determination-of-dendritic-spine-morphology-by-the-striatin-scaffold-protein-strn4-through-interaction-with-the-phosphatase-pp2a
#3
Lianfeng Lin, Louisa Hoi-Ying Lo, Quanwei Lyu, Kwok-On Lai
Dendritic spines are heterogeneous and exist with various morphologies. Altered spine morphology might underlie the cognitive deficits in neurodevelopmental disorders such as autism, but how different subtypes of dendritic spines are selectively maintained along development is still poorly understood. Spine maturation requires spontaneous activity of N-methyl-D-aspartate (NMDA) receptor and local dendritic protein synthesis. STRN4 (also called Zinedin) belongs to the striatin family of scaffold proteins, and some of the potential striatin-interacting proteins are encoded by autism risk genes...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#4
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28430606/ketamine-administered-pregnant-rats-impair-learning-and-memory-in-offspring-via-the-creb-pathway
#5
Xinran Li, Cen Guo, Yanan Li, Lina Li, Yuxin Wang, Yiming Zhang, Yue Li, Yu Chen, Wenhan Liu, Li Gao
Ketamine has been reported to impair the capacity for learning and memory. This study examined whether these capacities were also altered in the offspring and investigated the role of the CREB signaling pathway in pregnant rats, subjected to ketamine-induced anesthesia. On the 14th day of gestation (P14), female rats were anesthetized for 3 h via intravenous ketamine injection (200 mg/Kg). Morris water maze task, contextual and cued fear conditioning, and olfactory tasks were executed between the 25th to 30th day after birth (B25-30) on rat pups, and rats were sacrificed on B30...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426966/assembly-of-excitatory-synapses-in-the-absence-of-glutamatergic-neurotransmission
#6
Richard Sando, Eric Bushong, Yongchuan Zhu, Min Huang, Camille Considine, Sebastien Phan, Suyeon Ju, Marco Uytiepo, Mark Ellisman, Anton Maximov
Synaptic excitation mediates a broad spectrum of structural changes in neural circuits across the brain. Here, we examine the morphologies, wiring, and architectures of single synapses of projection neurons in the murine hippocampus that developed in virtually complete absence of vesicular glutamate release. While these neurons had smaller dendritic trees and/or formed fewer contacts in specific hippocampal subfields, their stereotyped connectivity was largely preserved. Furthermore, loss of release did not disrupt the morphogenesis of presynaptic terminals and dendritic spines, suggesting that glutamatergic neurotransmission is unnecessary for synapse assembly and maintenance...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426965/formation-and-maintenance-of-functional-spines-in-the-absence-of-presynaptic-glutamate-release
#7
Albrecht Sigler, Won Chan Oh, Cordelia Imig, Bekir Altas, Hiroshi Kawabe, Benjamin H Cooper, Hyung-Bae Kwon, Jeong-Seop Rhee, Nils Brose
Dendritic spines are the major transmitter reception compartments of glutamatergic synapses in most principal neurons of the mammalian brain and play a key role in the function of nerve cell circuits. The formation of functional spine synapses is thought to be critically dependent on presynaptic glutamatergic signaling. By analyzing CA1 pyramidal neurons in mutant hippocampal slice cultures that are essentially devoid of presynaptic transmitter release, we demonstrate that the formation and maintenance of dendrites and functional spines are independent of synaptic glutamate release...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28423315/mir-132-212-modulates-seasonal-adaptation-and-dendritic-morphology-of-the-central-circadian-clock
#8
Lucia Mendoza-Viveros, Cheng-Kang Chiang, Jonathan L K Ong, Sara Hegazi, Arthur H Cheng, Pascale Bouchard-Cannon, Michael Fana, Christopher Lowden, Peng Zhang, Béatrice Bothorel, Matthew G Michniewicz, Stephen T Magill, Melissa M Holmes, Richard H Goodman, Valérie Simonneaux, Daniel Figeys, Hai-Ying M Cheng
The central circadian pacemaker, the suprachiasmatic nucleus (SCN), encodes day length information by mechanisms that are not well understood. Here, we report that genetic ablation of miR-132/212 alters entrainment to different day lengths and non-24 hr day-night cycles, as well as photoperiodic regulation of Period2 expression in the SCN. SCN neurons from miR-132/212-deficient mice have significantly reduced dendritic spine density, along with altered methyl CpG-binding protein (MeCP2) rhythms. In Syrian hamsters, a model seasonal rodent, day length regulates spine density on SCN neurons in a melatonin-independent manner, as well as expression of miR-132, miR-212, and their direct target, MeCP2...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28422010/synaptic-input-sequence-discrimination-on-behavioral-time-scales-mediated-by-reaction-diffusion-chemistry-in-dendrites
#9
Upinder Singh Bhalla
Sequences of events are ubiquitous in sensory, motor, and cognitive function. Key computational operations, including pattern recognition, event prediction, and plasticity, involve neural discrimination of spatio-temporal sequences. Here we show that synaptically-driven reaction-diffusion pathways on dendrites can perform sequence discrimination on behaviorally relevant time-scales. We used abstract signaling models to show that selectivity arises when inputs at successive locations are aligned with, and amplified by, propagating chemical waves triggered by previous inputs...
April 19, 2017: ELife
https://www.readbyqxmd.com/read/28421537/satb2-ablation-impairs-hippocampus-based-long-term-spatial-memory-and-short-term-working-memory-and-immediate-early-genes-iegs-mediated-hippocampal-synaptic-plasticity
#10
Ying Li, Qiang-Long You, Sheng-Rong Zhang, Wei-Yuan Huang, Wen-Jun Zou, Wei Jie, Shu-Ji Li, Ji-Hong Liu, Chuang-Ye Lv, Jin Cong, Yu-Ying Hu, Tian-Ming Gao, Jian-Ming Li
Special AT-rich sequence-binding protein 2 (Satb2) is a protein binding to the matrix attachment regions of DNA and important for gene regulation. Patients with SATB2 mutation usually suffer moderate to severe mental retardation. However, the mechanisms for the defects of intellectual activities in patients with SATB2 mutation are largely unclear. Here we established the heterozygous Satb2 mutant mice and Satb2 conditional knockout mice to mimic the patients with SATB2 mutation and figured out the role of Satb2 in mental activities...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28417997/iterative-expansion-microscopy
#11
Jae-Byum Chang, Fei Chen, Young-Gyu Yoon, Erica E Jung, Hazen Babcock, Jeong Seuk Kang, Shoh Asano, Ho-Jun Suk, Nikita Pak, Paul W Tillberg, Asmamaw T Wassie, Dawen Cai, Edward S Boyden
We recently developed a method called expansion microscopy, in which preserved biological specimens are physically magnified by embedding them in a densely crosslinked polyelectrolyte gel, anchoring key labels or biomolecules to the gel, mechanically homogenizing the specimen, and then swelling the gel-specimen composite by ∼4.5× in linear dimension. Here we describe iterative expansion microscopy (iExM), in which a sample is expanded ∼20×. After preliminary expansion a second swellable polymer mesh is formed in the space newly opened up by the first expansion, and the sample is expanded again...
April 17, 2017: Nature Methods
https://www.readbyqxmd.com/read/28416631/mutation-of-neuron-specific-chromatin-remodeling-subunit-baf53b-rescue-of-plasticity-and-memory-by-manipulating-actin-remodeling
#12
Annie Vogel Ciernia, Enikö A Kramár, Dina P Matheos, Robbert Havekes, Thekla J Hemstedt, Christophe N Magnan, Keith Sakata, Ashley Tran, Soraya Azzawi, Alberto Lopez, Richard Dang, Weisheng Wang, Brian Trieu, Joyce Tong, Ruth M Barrett, Rebecca J Post, Pierre Baldi, Ted Abel, Gary Lynch, Marcelo A Wood
Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons...
May 2017: Learning & Memory
https://www.readbyqxmd.com/read/28415680/long-term-neurocognitive-dysfunction-in-offspring-via-ngf-erk-creb-signaling-pathway-caused-by-ketamine-exposure-during-the-second-trimester-of-pregnancy-in-rats
#13
Yanan Li, Xinran Li, Cen Guo, Lina Li, Yuxin Wang, Yiming Zhang, Yu Chen, Wenhan Liu, Li Gao
Early life exposure to ketamine caused neurohistopathologic changes and persistent cognitive dysfunction. For this study, a pregnant rat model was developed to investigate neurocognitive effects in the offspring, following ketamine exposure during the second trimester. Pregnant rats on gestational day 14 (equal to midtrimester pregnancy in humans), intravenously received 200 mg/kg ketamine for 3 h. Their behavior was tested (Morris water maze, odor recognition test, and fear conditioning) at postnatal days (P25-30)...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414299/an-indirect-route-to-repetitive-actions
#14
David M Lovinger
It is increasingly evident that there is a genetic contribution to autism spectrum disorders (ASDs) and other neural disorders involving excessive repetition of action sequences. Among the implicated genes in these disorders are those encoding postsynaptic scaffolding proteins with roles in synaptic transmission and plasticity. Several mouse models harboring synonymous mutations have shown alterations in synaptic transmission within the striatum, which has key roles in controlling actions and action sequences...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28406977/separation-increases-passive-stress-coping-behaviors-during-forced-swim-and-alters-hippocampal-dendritic-morphology-in-california-mice
#15
Molly M Hyer, Erica R Glasper
Individuals within monogamous species form bonds that may buffer against the negative effects of stress on physiology and behavior. In some species, involuntary termination of the mother-offspring bond results in increased symptoms of negative affect in the mother, suggesting that the parent-offspring bond may be equally as important as the pair bond. To our knowledge, the extent to which affect in paternal rodents is altered by involuntary termination of the father-offspring bond is currently unknown. Here, we investigated to what extent separation and paternal experience alters passive stress-coping behaviors and dendritic morphology in hippocampal subfields of California mice (Peromyscus californicus)...
2017: PloS One
https://www.readbyqxmd.com/read/28404748/components-of-rna-granules-affect-their-localization-and-dynamics-in-neuronal-dendrites
#16
Kazuhiko Mitsumori, Yosuke Takei, Nobutaka Hirokawa
In neurons, RNA transport is important for local protein synthesis. Messenger RNAs (mRNAs) are transported along dendrites as large RNA granules. The localization and dynamics of Puralpha and Stau1, major components of RNA transport granules, were investigated in cultured hippocampal neurons. Puralpha-positive granules were localized in both the shafts and spines of dendrites. In contrast, Stau1-positive granules tended to be localized mainly in dendritic shafts. More than 90% of Puralpha-positive granules were positive for Stau1 in immature dendrites, while only half were positive in mature dendrites...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28402855/stim1-ca-2-sensor-control-of-l-type-ca-2-channel-dependent-dendritic-spine-structural-plasticity-and-nuclear-signaling
#17
Philip J Dittmer, Angela R Wild, Mark L Dell'Acqua, William A Sather
Potentiation of synaptic strength relies on postsynaptic Ca(2+) signals, modification of dendritic spine structure, and changes in gene expression. One Ca(2+) signaling pathway supporting these processes routes through L-type Ca(2+) channels (LTCC), whose activity is subject to tuning by multiple mechanisms. Here, we show in hippocampal neurons that LTCC inhibition by the endoplasmic reticulum (ER) Ca(2+) sensor, stromal interaction molecule 1 (STIM1), is engaged by the neurotransmitter glutamate, resulting in regulation of spine ER structure and nuclear signaling by the NFATc3 transcription factor...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28400058/the-snk-and-spar-signaling-pathway-changes-in-hippocampal-neurons-treated-with-amyloid-beta-peptide-in-vitro
#18
Hua Sui, Libin Zhan, Xinping Niu, Lina Liang, Xin Li
Amyloid-β peptide (Aβ) is believed to be a primary cause of Alzheimer's disease. Many studies have demonstrated that Aβ causes morphological and functional alterations of dendritic spines, leading to synaptic dysfunction, but the effect of Aβ on damage to synaptic functions is not fully understood. Spine-associated Rap guanosine triphosphatase-activating protein (SPAR) is an important regulator of activity-dependent remodeling of synapses and is critically involved in both mature dendritic spine formation and the maintenance of spine maturity...
March 22, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28398234/down-regulated-drebrin-aggravates-cognitive-impairments-in-a-mouse-model-of-alzheimer-s-disease
#19
Yan Liu, Yanfeng Xu, Ling Zhang, Lan Huang, Pin Yu, Hua Zhu, Wei Deng, Chuan Qin
The developmentally regulated brain protein drebrin (Dbn) is a functional protein involved with long-term memory formation and is widely distributed in brain neurons, especially in the dendritic spines. A noticeable decline of this protein has been found in the hippocampus and cortex of patients with Alzheimer's disease (AD), yet the relationship between Dbn and AD has not been fully understood. In the present study, we examined how down-regulation of Dbn impacts the progression of AD in experimental animals...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28396402/apc-c-cdh1-rock2-pathway-controls-dendritic-integrity-and-memory
#20
Verónica Bobo-Jiménez, María Delgado-Esteban, Julie Angibaud, Irene Sánchez-Morán, Antonio de la Fuente, Javier Yajeya, U Valentin Nägerl, José Castillo, Juan P Bolaños, Angeles Almeida
Disruption of neuronal morphology contributes to the pathology of neurodegenerative disorders such as Alzheimer's disease (AD). However, the underlying molecular mechanisms are unknown. Here, we show that postnatal deletion of Cdh1, a cofactor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase in neurons [Cdh1 conditional knockout (cKO)], disrupts dendrite arborization and causes dendritic spine and synapse loss in the cortex and hippocampus, concomitant with memory impairment and neurodegeneration, in adult mice...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
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