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Neuron

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https://www.readbyqxmd.com/read/28416077/blood-brain-barrier-permeability-is-regulated-by-lipid-transport-dependent-suppression-of-caveolae-mediated-transcytosis
#1
Benjamin J Andreone, Brian Wai Chow, Aleksandra Tata, Baptiste Lacoste, Ayal Ben-Zvi, Kevin Bullock, Amy A Deik, David D Ginty, Clary B Clish, Chenghua Gu
The blood-brain barrier (BBB) provides a constant homeostatic brain environment that is essential for proper neural function. An unusually low rate of vesicular transport (transcytosis) has been identified as one of the two unique properties of CNS endothelial cells, relative to peripheral endothelial cells, that maintain the restrictive quality of the BBB. However, it is not known how this low rate of transcytosis is achieved. Here we provide a mechanism whereby the regulation of CNS endothelial cell lipid composition specifically inhibits the caveolae-mediated transcytotic route readily used in the periphery...
April 11, 2017: Neuron
https://www.readbyqxmd.com/read/28238551/molecular-mechanism-of-ampa-receptor-modulation-by-tarp-stargazin
#2
Anat Ben-Yaacov, Moshe Gillor, Tomer Haham, Alon Parsai, Mohammad Qneibi, Yael Stern-Bach
AMPA receptors (AMPARs) mediate the majority of fast excitatory transmission in the brain and critically contribute to synaptic plasticity and pathology. AMPAR trafficking and gating are tightly controlled by auxiliary transmembrane AMPAR regulatory proteins (TARPs). Here, using systematic domain swaps with the TARP-insensitive kainate receptor GluK2, we show that AMPAR interaction with the prototypical TARP stargazin/γ2 primarily involves the AMPAR membrane domains M1 and M4 of neighboring subunits, initiated or stabilized by the AMPAR C-tail, and that these interactions are sufficient to enable full receptor modulation...
February 17, 2017: Neuron
https://www.readbyqxmd.com/read/28238547/hallmarks-of-alzheimer-s-disease-in-stem-cell-derived-human-neurons-transplanted-into-mouse-brain
#3
Ira Espuny-Camacho, Amaia M Arranz, Mark Fiers, An Snellinx, Kunie Ando, Sebastian Munck, Jerome Bonnefont, Laurie Lambot, Nikky Corthout, Lorna Omodho, Elke Vanden Eynden, Enrico Radaelli, Ina Tesseur, Selina Wray, Andreas Ebneth, John Hardy, Karelle Leroy, Jean-Pierre Brion, Pierre Vanderhaeghen, Bart De Strooper
Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration...
February 15, 2017: Neuron
https://www.readbyqxmd.com/read/28215557/long-term-two-photon-imaging-in-awake-macaque-monkey
#4
Ming Li, Fang Liu, Hongfei Jiang, Tai Sing Lee, Shiming Tang
Successful application of two-photon imaging with genetic tools in awake macaque monkeys will enable fundamental advances in our understanding of higher cognitive function at the level of molecular and neuronal circuits. Here we report techniques for long-term two-photon imaging in awake macaque monkeys. Using genetically encoded indicators including GCaMP5 and GCaMP6s delivered by AAV2/1 into the visual cortex, we demonstrate that high-quality two-photon imaging of large neuronal populations can be achieved and maintained in awake monkeys for months...
February 8, 2017: Neuron
https://www.readbyqxmd.com/read/28426971/metaplasticity-as-a-neural-substrate-for-adaptive-learning-and-choice-under-uncertainty
#5
Shiva Farashahi, Christopher H Donahue, Peyman Khorsand, Hyojung Seo, Daeyeol Lee, Alireza Soltani
Value-based decision making often involves integration of reward outcomes over time, but this becomes considerably more challenging if reward assignments on alternative options are probabilistic and non-stationary. Despite the existence of various models for optimally integrating reward under uncertainty, the underlying neural mechanisms are still unknown. Here we propose that reward-dependent metaplasticity (RDMP) can provide a plausible mechanism for both integration of reward under uncertainty and estimation of uncertainty itself...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426970/thalamic-regulation-of-sucrose-seeking-during-unexpected-reward-omission
#6
Fabricio H Do-Monte, Angélica Minier-Toribio, Kelvin Quiñones-Laracuente, Estefanía M Medina-Colón, Gregory J Quirk
The paraventricular nucleus of the thalamus (PVT) is thought to regulate behavioral responses under emotionally arousing conditions. Reward-associated cues activate PVT neurons; however, the specific PVT efferents regulating reward seeking remain elusive. Using a cued sucrose-seeking task, we manipulated PVT activity under two emotionally distinct conditions: (1) when reward was available during the cue as expected or (2) when reward was unexpectedly omitted during the cue. Pharmacological inactivation of the anterior PVT (aPVT), but not the posterior PVT, increased sucrose seeking only when reward was omitted...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426969/chemogenetic-interrogation-of-a-brain-wide-fear-memory-network-in-mice
#7
Gisella Vetere, Justin W Kenney, Lina M Tran, Frances Xia, Patrick E Steadman, John Parkinson, Sheena A Josselyn, Paul W Frankland
Behavior depends on coordinated activity across multiple brain regions. Within such networks, highly connected hub regions are assumed to disproportionately influence behavioral output, although this hypothesis has not been systematically evaluated. Previously, by mapping brain-wide expression of the activity-regulated gene c-fos, we identified a network of brain regions co-activated by fear memory. To test the hypothesis that hub regions are more important for network function, here, we simulated node deletion in silico in this behaviorally defined functional network...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426968/map2-defines-a-pre-axonal-filtering-zone-to-regulate-kif1-versus-kif5-dependent-cargo-transport-in-sensory-neurons
#8
Laura F Gumy, Eugene A Katrukha, Ilya Grigoriev, Dick Jaarsma, Lukas C Kapitein, Anna Akhmanova, Casper C Hoogenraad
Polarized cargo transport is essential for neuronal function. However, the minimal basic components required for selective cargo sorting and distribution in neurons remain elusive. We found that in sensory neurons the axon initial segment is largely absent and that microtubule-associated protein 2 (MAP2) defines the cargo-filtering zone in the proximal axon. Here, MAP2 directs axonal cargo entry by coordinating the activities of molecular motors. We show that distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426967/an-intrinsic-epigenetic-barrier-for-functional-axon-regeneration
#9
Yi-Lan Weng, Ran An, Jessica Cassin, Jessica Joseph, Ruifa Mi, Chen Wang, Chun Zhong, Seung-Gi Jin, Gerd P Pfeifer, Alfonso Bellacosa, Xinzhong Dong, Ahmet Hoke, Zhigang He, Hongjun Song, Guo-Li Ming
Mature neurons in the adult peripheral nervous system can effectively switch from a dormant state with little axonal growth to robust axon regeneration upon injury. The mechanisms by which injury unlocks mature neurons' intrinsic axonal growth competence are not well understood. Here, we show that peripheral sciatic nerve lesion in adult mice leads to elevated levels of Tet3 and 5-hydroxylmethylcytosine in dorsal root ganglion (DRG) neurons. Functionally, Tet3 is required for robust axon regeneration of DRG neurons and behavioral recovery...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426966/assembly-of-excitatory-synapses-in-the-absence-of-glutamatergic-neurotransmission
#10
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
#11
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/28426964/ipsc-derived-human-microglia-like-cells-to-study-neurological-diseases
#12
Edsel M Abud, Ricardo N Ramirez, Eric S Martinez, Luke M Healy, Cecilia H H Nguyen, Sean A Newman, Andriy V Yeromin, Vanessa M Scarfone, Samuel E Marsh, Cristhian Fimbres, Chad A Caraway, Gianna M Fote, Abdullah M Madany, Anshu Agrawal, Rakez Kayed, Karen H Gylys, Michael D Cahalan, Brian J Cummings, Jack P Antel, Ali Mortazavi, Monica J Carson, Wayne W Poon, Mathew Blurton-Jones
Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGLs) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer's disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo, and whole-transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426963/heterologous-expression-of-the-piezo1-asic1-chimera-induces-mechanosensitive-currents-with-properties-distinct-from-piezo1
#13
Qiancheng Zhao, Kun Wu, Shaopeng Chi, Jie Geng, Bailong Xiao
Piezo1 represents a prototype of the mammalian mechanosensitive cation channel, but its molecular mechanism remains elusive. In a recent study, we showed that C-terminal region, which contains the last two TMs, of 2189-2547 of Piezo1 forms the bona fide pore module, and systematically identified the pore-lining helix and key pore-property-determining residues (Zhao et al., 2016). Furthermore, we have engineered the Piezo1(1-2190)-ASIC1 chimera (fusing the N-terminal region of 1-2190 to the mechano-insensitive ASIC1) that mediated mechanical- and acid-evoked currents in HEK293T cells, indicating the sufficiency of the N-terminal region in mechanotransduction...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426962/evidence-for-mechanosensitive-channel-activity-of-tentonin-3-tmem150c
#14
Gyu-Sang Hong, Byeongjun Lee, Uhtaek Oh
Mechanosensation is essential for various physiological processes, and it is mediated by mechanotransduction channels. Recently, we reported that TMEM150C/Tentonin 3 (TTN3) confers mechanically activated currents with slow inactivation kinetics in several cell types, including dorsal root ganglion neurons (Hong et al., 2016). The accompanying Matters Arising by Dubin, Murthy, and colleagues confirms that naive heterologous cells demonstrate a mechanically activated current, but finds that this response is absent in CRISPR-Cas9 Piezo1 knockout cell lines and suggests that TTN3 is a modulator of Piezo1...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426961/endogenous-piezo1-can-confound-mechanically-activated-channel-identification-and-characterization
#15
Adrienne E Dubin, Swetha Murthy, Amanda H Lewis, Lucie Brosse, Stuart M Cahalan, Jörg Grandl, Bertrand Coste, Ardem Patapoutian
A gold standard for characterizing mechanically activated (MA) currents is via heterologous expression of candidate channels in naive cells. Two recent studies described MA channels using this paradigm. TMEM150c was proposed to be a component of an MA channel partly based on a heterologous expression approach (Hong et al., 2016). In another study, Piezo1's N-terminal "propeller" domain was proposed to constitute an intrinsic mechanosensitive module based on expression of a chimera between a pore-forming domain of the mechanically insensitive ASIC1 channel and Piezo1 (Zhao et al...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426960/editorial-note-to-endogenous-piezo1-can-confound-mechanically-activated-channel-identification-and-characterization
#16
Adrienne E Dubin, Swetha Murthy, Amanda H Lewis, Lucie Brosse, Stuart M Cahalan, Jörg Grandl, Bertrand Coste, Ardem Patapoutian
No abstract text is available yet for this article.
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426959/ontogenesis-of-lateralization
#17
REVIEW
Onur Güntürkün, Sebastian Ocklenburg
The brains of humans and other animals are asymmetrically organized, but we still know little about the ontogenetic and neural fundaments of lateralizations. Here, we review the current state of understanding about the role of genetic and non-genetic factors for the development of neural and behavioral asymmetries in vertebrates. At the genetic level, the Nodal signaling cascade is of central importance, but several other genetic pathways have been discovered to also shape the lateralized embryonic brain. Studies in humans identified several relevant genes with mostly small effect sizes but also highlight the extreme importance of non-genetic factors for asymmetry development...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426958/elucidating-the-role-of-trem2-in-alzheimer-s-disease
#18
REVIEW
Jason D Ulrich, Tyler K Ulland, Marco Colonna, David M Holtzman
Alzheimer's disease (AD) is the sixth leading cause of death in the United States and the most common cause of dementia in the elderly. Genetic factors, such as rare variants in the microglial-expressed gene TREM2, strongly impact the lifetime risk of developing AD. Several recent studies have described dramatic TREM2-dependent phenotypes in mouse models of amyloidosis that point to an important role for TREM2 in regulating the response of the innate immune system to Aβ pathology. Furthermore, elevations in the CSF levels of soluble TREM2 fragments implicate changes in inflammatory pathways as occurring coincident with markers of neuronal damage and the onset of clinical dementia in AD...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426957/emerging-global-initiatives-in-neurogenetics-the-enhancing-neuroimaging-genetics-through-meta-analysis-enigma-consortium
#19
Carrie E Bearden, Paul M Thompson
The Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) Consortium is a global team science effort, now including over 800 scientists spread across 340 institutions in 35 countries, with the shared goal of understanding disease and genetic influences on the brain. This "crowdsourcing" approach to team neuroscience has unprecedented power for advancing our understanding of both typical and atypical human brain development.
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426956/amines-astrocytes-and-arousal
#20
Narges Bazargani, David Attwell
Amine neurotransmitters, such as noradrenaline, mediate arousal, attention, and reward in the CNS. New data suggest that, from flies to mammals, a major mechanism for amine transmitter action is to raise astrocyte [Ca(2+)]i and release gliotransmitters that modulate neuronal activity and behavior.
April 19, 2017: Neuron
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