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https://www.readbyqxmd.com/read/28822839/decreased-surface-expression-of-the-%C3%AE-subunit-of-the-gabaa-receptor-contributes-to-reduced-tonic-inhibition-in-dentate-granule-cells-in-a-mouse-model-of-fragile-x-syndrome
#1
Nianhui Zhang, Zechun Peng, Xiaoping Tong, A Kerstin Lindemeyer, Yliana Cetina, Christine S Huang, Richard W Olsen, Thomas S Otis, Carolyn R Houser
While numerous changes in the GABA system have been identified in models of Fragile X Syndrome (FXS), alterations in subunits of the GABAA receptors (GABAARs) that mediate tonic inhibition are particularly intriguing. Considering the key role of tonic inhibition in controlling neuronal excitability, reduced tonic inhibition could contribute to FXS-associated disorders such as hyperactivity, hypersensitivity, and increased seizure susceptibility. The current study has focused on the expression and function of the δ subunit of the GABAAR, a major subunit involved in tonic inhibition, in granule cells of the dentate gyrus in the Fmr1 knockout (KO) mouse model of FXS...
August 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28822835/neuroprotective-effects-of-acetyl-l-carnitine-on-lipopolysaccharide-induced-neuroinflammation-in-mice-involvement-of-brain-derived-neurotrophic-factor
#2
Filiz Kazak, Gul Fatma Yarim
Neuroinflammation is the inflammation of nervous tissue that can lead to neurodegeneration. Brain-derived neurotrophic factor (BDNF) is a neurotrophin which affects growth, function and survival of neurons, enhances the stabilization of synapses, regulates synaptic function and branching of dendrites and axons. Brain-derived neurotrophic factor is believed to be involved in the pathophysiology of central nervous system (CNS) diseases associated with neuroinflamation. The aim of this study was to investigate new protective and therapeutic effect of acetyl-L-carnitine (ALCAR) in neuroinflammation...
August 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28822075/recycling-endosomes-in-human-cytotoxic-t-lymphocytes-constitute-an-auxiliary-intracellular-trafficking-pathway-for-newly-synthesized-perforin
#3
Kelsey Lesteberg, Jordan Orange, George Makedonas
Although cytotoxic T lymphocytes (CTLs) store perforin within cytoplasmic secretory granules for immediate use, perforin is synthesized anew within hours of TCR stimulation. Previously, we observed new perforin protein at an immunologic synapse independent of secretory lysosomes; herein, we aimed to determine how new perforin transits to the synapse if not via lytic granules. We analyzed antigen-specific human CTLs via imaging flow cytometry and high-resolution confocal microscopy, with attention to intracellular trafficking components and new perforin...
August 18, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28821864/nanomechanics-of-multidomain-neuronal-cell-adhesion-protein-contactin-revealed-by-single-molecule-afm-and-smd
#4
K Mikulska-Ruminska, A J Kulik, C Benadiba, I Bahar, G Dietler, W Nowak
Contactin-4 (CNTN4) is a complex cell adhesion molecule (CAM) localized at neuronal membranes, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. CNTN4 consists of six immunoglobulin C2 type (IgC2) domains and four fibronectin type III (FnIII) domains that are shared with many other CAMs. Mutations in CNTN4 gene have been linked to various psychiatric disorders. Toward elucidating the response of this modular protein to mechanical stress, we studied its force-induced unfolding using single molecule atomic force microscopy (smAFM) and steered molecular dynamics (SMD) simulations...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821669/transcriptomic-analysis-of-ribosome-bound-mrna-in-cortical-neurites-in-vivo
#5
Rebecca Ouwenga, Allison M Lake, David O'Brien, Amit Mogha, Adish Dani, Joseph D Dougherty
Localized translation in neurites helps regulate synaptic strength and development. Dysregulation of local translation is associated with many neurological disorders. However, due to technical limitations, study of this phenomenon has largely been limited to brain regions with laminar organization of dendrites such as the hippocampus or cerebellum. It has not been examined in the cortex, a region of importance for most neurological disorders, where dendrites of each neuronal population are densely intermingled with cell bodies of others...
August 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821654/wnt9a-can-influence-cell-fates-and-neural-connectivity-across-the-radial-axis-of-the-developing-cochlea
#6
Vidhya Munnamalai, Ulrike J Sienknecht, R Keith Duncan, M Katie Scott, Ankita Thawani, Kristen N Fantetti, Nadia M Atallah, Deborah J Biesemeier, Kuhn H Song, Kirsten Luethy, Eric Traub, Donna M Fekete
Vertebrate hearing organs manifest cellular asymmetries across the radial axis that underlie afferent versus efferent circuits between the inner ear and the brain. Thus, understanding the molecular control of patterning across this axis has important functional implications. Radial axis patterning begins before the cells become postmitotic, and is likely linked to the onset of asymmetric expression of secreted factors adjacent to the sensory primordium. This study explores one such asymmetrically-expressed gene, Wnt9a, that becomes restricted to the neural edge of the avian auditory organ, the basilar papilla, by embryonic day (E) 5...
August 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821276/inflammatory-demyelination-alters-subcortical-visual-circuits
#7
Sheila Espírito Santo Araújo, Henrique Rocha Mendonça, Natalie A Wheeler, Paula Campello-Costa, Kimberle M Jacobs, Flávia C A Gomes, Michael A Fox, Babette Fuss
BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease classically associated with axonal damage and loss; more recently, however, synaptic changes have been recognized as additional contributing factors. An anatomical area commonly affected in MS is the visual pathway; yet, changes other than those associated with inflammatory demyelination of the optic nerve, i.e., optic neuritis, have not been described in detail. METHODS: Adult mice were subjected to a diet containing cuprizone to mimic certain aspects of inflammatory demyelination as seen in MS...
August 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28820903/prominent-facilitation-at-beta-and-gamma-frequency-range-revealed-with-physiological-calcium-concentration-in-adult-mouse-piriform-cortex-in-vitro
#8
Marie Gleizes, Simon P Perrier, Caroline Fonta, Lionel G Nowak
Neuronal activity is characterized by a diversity of oscillatory phenomena that are associated with multiple behavioral and cognitive processes, yet the functional consequences of these oscillations are not fully understood. Our aim was to determine whether and how these different oscillatory activities affect short-term synaptic plasticity (STP), using the olfactory system as a model. In response to odorant stimuli, the olfactory bulb displays a slow breathing rhythm as well as beta and gamma oscillations...
2017: PloS One
https://www.readbyqxmd.com/read/28820141/silicon-synaptic-transistor-for-hardware-based-spiking-neural-network-and-neuromorphic-system
#9
Hyungjin Kim, Sungmin Hwang, Jungjin Park, Byung-Gook Park
Brain-inspired neuromorphic systems have attracted much attention as new computing paradigms for power-efficient computation. Here, we report a silicon synaptic transistor with two electrically independent gates to realize a hardware-based neural network system without any switching components. The spike-timing dependent plasticity (STDP) characteristics of the synaptic devices are measured and analyzed. With the help of the device model based on the measured data, the pattern recognition capability of the hardware-based spiking neural network (SNN) systems is demonstrated using the modified national institute of standards and technology (MNIST) handwritten dataset...
August 18, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28819795/leptin-regulation-of-synaptic-function-at-hippocampal-ta-ca1-and-sc-ca1-synapses-implications-for-health-and-disease
#10
Gemma McGregor, Jenni Harvey
Growing evidence indicates that the endocrine hormone leptin regulates hippocampal synaptic function in addition to its established role as a hypothalamic satiety signal. Indeed, numerous studies show that leptin facilitates the cellular events that underlie hippocampal learning and memory including activity-dependent synaptic plasticity and glutamate receptor trafficking, indicating that leptin may be a potential cognitive enhancer. Although there has been extensive investigation into the modulatory role of leptin at hippocampal Schaffer collateral (SC)-CA1 synapses, recent evidence indicates that leptin also potently regulates excitatory synaptic transmission at the anatomically distinct temporoammonic (TA) input to hippocampal CA1 neurons...
August 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28819108/spag6-mutant-mice-have-defects-in-development-and-function-of-spiral-ganglion-neurons-apoptosis-and-higher-sensitivity-to-paclitaxel
#11
Xiaofei Li, Lei Xu, Gaoying Sun, Xianmin Wu, Xiaohui Bai, Jianfeng Li, Jerome F Strauss, Zhibing Zhang, Haibo Wang
Mammalian Sperm Associated Antigen 6 (SPAG6) is the orthologue of Chlamydomonas PF16, a protein localized in the axoneme central apparatus. Recent studies showed that Spag6 has a role in brain neuronal proliferation and differentiation. The mammalian spiral ganglion neurons (SGNs) are specialzed bipolar neurons in the inner ear. However, the role of SPAG6 in SGN has not been elucidated. Therefore, We hypothesized that a Spag6 knockout would affect the development and function of SGNs. We utilized Spag6-deficient mice and SGN explants to define the role of SPAG6...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819053/novel-neurobiological-properties-of-elements-in-the-escape-circuitry-of-the-shrimp
#12
De Forest Mellon
Escape behaviors in peneid shrimp are mediated by large myelinated medial giant fibers which course from the brain to the last abdominal ganglion in the ventral nerve cord. In each abdominal segment the medial giant axons make synaptic connections with paired myelinated giant motor axons that excite the abdominal deep flexor muscles and drive the tailflips that constitute the escape behavior. I examined 1) anatomical features of the abdominal motor giant fibers and 2) electrical properties of both the medial giants and motor giants in the pink shrimp, Farfantepenaeus duoarum...
August 17, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28818091/non-canonical-soluble-amyloid-beta-aggregates-and-plaque-buffering-controversies-and-future-directions-for-target-discovery-in-alzheimer-s-disease
#13
REVIEW
David L Brody, Hao Jiang, Norelle Wildburger, Thomas J Esparza
The specific amyloid-beta (Aβ) species or other amyloid-precursor protein cleavage products that are most directly related to human neurodegeneration and clinical dementia of the Alzheimer's type have not yet been directly identified. Without a clear understanding of the most relevant species, it is difficult to determine whether therapeutic candidates successfully engaged the correct target(s). Here, we review some of the controversies regarding soluble Aβ aggregates (also termed oligomers, dimers, trimers, Aβ*56, amylospheroids, etc...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28817805/ltp-at-hilar-mossy-cell-dentate-granule-cell-synapses-modulates-dentate-gyrus-output-by-increasing-excitation-inhibition-balance
#14
Yuki Hashimotodani, Kaoutsar Nasrallah, Kyle R Jensen, Andrés E Chávez, Daniel Carrera, Pablo E Castillo
Excitatory hilar mossy cells (MCs) in the dentate gyrus receive inputs from dentate granule cells (GCs) and project back to GCs locally, contralaterally, and along the longitudinal axis of the hippocampus, thereby establishing an associative positive-feedback loop and connecting functionally diverse hippocampal areas. MCs also synapse with GABAergic interneurons that mediate feed-forward inhibition onto GCs. Surprisingly, although these circuits have been implicated in both memory formation (e.g., pattern separation) and temporal lobe epilepsy, little is known about activity-dependent plasticity of their synaptic connections...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817804/structural-mechanism-for-modulation-of-synaptic-neuroligin-neurexin-signaling-by-mdga-proteins
#15
Jonathan Elegheert, Vedrana Cvetkovska, Amber J Clayton, Christina Heroven, Kristel M Vennekens, Samuel N Smukowski, Michael C Regan, Wanyi Jia, Alexandra C Smith, Hiro Furukawa, Jeffrey N Savas, Joris de Wit, Jo Begbie, Ann Marie Craig, A Radu Aricescu
Neuroligin-neurexin (NL-NRX) complexes are fundamental synaptic organizers in the central nervous system. An accurate spatial and temporal control of NL-NRX signaling is crucial to balance excitatory and inhibitory neurotransmission, and perturbations are linked with neurodevelopmental and psychiatric disorders. MDGA proteins bind NLs and control their function and interaction with NRXs via unknown mechanisms. Here, we report crystal structures of MDGA1, the NL1-MDGA1 complex, and a spliced NL1 isoform. Two large, multi-domain MDGA molecules fold into rigid triangular structures, cradling a dimeric NL to prevent NRX binding...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817794/a-triad-of-crystals-sheds-light-on-mdga-interference-with-neuroligation
#16
Olivier Thoumine, Pascale Marchot
Neurexins and neuroligins form trans-synaptic complexes that promote synapse development. In this issue of Neuron, Aricescu and colleagues (Elegheert et al., 2017) complement and strengthen two recent reports by the Kim and Rudenko teams (Kim et al., 2017; Gangwar et al., 2017) to dissect the molecular determinants by which MDGAs challenge the neurexin-neuroligin partnership.
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817635/contractile-actomyosin-arcs-promote-the-activation-of-primary-mouse-t-cells-in-a-ligand-dependent-manner
#17
Jinsung Hong, Sricharan Murugesan, Eric Betzig, John A Hammer
Mechano-transduction is an emerging but still poorly understood component of T cell activation. Here we investigated the ligand-dependent contribution made by contractile actomyosin arcs populating the peripheral supramolecular activation cluster (pSMAC) region of the immunological synapse (IS) to T cell receptor (TCR) microcluster transport and proximal signaling in primary mouse T cells. Using super resolution microscopy, OT1-CD8+ mouse T cells, and two ovalbumin (OVA) peptides with different affinities for the TCR, we show that the generation of organized actomyosin arcs depends on ligand potency and the ability of myosin 2 to contract actin filaments...
2017: PloS One
https://www.readbyqxmd.com/read/28816653/assembly-rules-for-gabaa-receptor-complexes-in-the-brain
#18
James S Martenson, Tokiwa Yamasaki, Nashid H Chaudhury, David Albrecht, Susumu Tomita
GABAA receptor (GABAAR) pentamers are assembled from a pool of 19 subunits, and variety in subunit combinations diversifies GABAAR functions to tune brain activity. Pentamers with distinct subunit compositions localize differentially at synaptic and non-synaptic sites to mediate phasic and tonic inhibition, respectively. Despite multitudes of theoretical permutations, limited subunit combinations have been identified in the brain. Currently, no molecular model exists for combinatorial GABAAR assembly in vivo...
August 17, 2017: ELife
https://www.readbyqxmd.com/read/28815589/tight-temporal-coupling-between-synaptic-rewiring-of-olfactory-glomeruli-and-the-emergence-of-odor-guided-behavior-in-xenopus-tadpoles
#19
Beatrice Terni, Paolo Pacciolla, Helena Masanas, Pau Gorostiza, Artur Llobet
Olfactory sensory neurons (OSNs) are chemoreceptors that establish excitatory synapses within glomeruli of the olfactory bulb. OSNs undergo continuous turnover throughout life, causing the constant replacement of their synaptic contacts. Using Xenopus tadpoles as an experimental system to investigate rewiring of glomerular connectivity, we show that novel OSN synapses can transfer information immediately after formation, mediating an olfactory-guided behavior. Tadpoles recover the ability to detect amino acids four days after bilateral olfactory nerve transection...
August 17, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28815295/loss-of-kirrel-family-members-alters-glomerular-structure-and-synapse-numbers-in-the-accessory-olfactory-bulb
#20
Alexandra C Brignall, Reesha Raja, Alina Phen, Janet E A Prince, Emilie Dumontier, Jean-François Cloutier
The accessory olfactory system controls social and sexual behaviours in mice, both of which are critical for their survival. Vomeronasal sensory neuron (VSN) axons form synapses with mitral cell dendrites in glomeruli of the accessory olfactory bulb (AOB). Axons of VSNs expressing the same vomeronasal receptor (VR) converge into multiple glomeruli within spatially conserved regions of the AOB. Here, we have examined the role of the cell adhesion molecule Kirrel2 in the formation of glomeruli within the AOB...
August 16, 2017: Brain Structure & Function
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