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Andrei Tsentsevitsky, Leniz Nurullin, Evgeny Nikolsky, Artem Malomouzh
There is some evidence that glutamate (Glu) acts as a signaling molecule at vertebrate neuromuscular junctions where acetylcholine (ACh) serves as a neurotransmitter. In this study, performed on the cutaneous pectoris muscle of the frog Rana ridibunda, Glu receptor mechanisms that modulate ACh release processes were analyzed. Electrophysiological experiments showed that Glu reduces both spontaneous and evoked quantal secretion of ACh and synchronizes its release in response to electrical stimulation. Quisqualate, an agonist of ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors and metabotropic Group I mGlu receptors, also exerted Glu-like inhibitory effects on the secretion of ACh but had no effect on the kinetics of quantal release...
October 22, 2016: Journal of Neuroscience Research
Gordon X Wang, Stephen J Smith, Philippe Mourrain
The distribution of proteins within sub-synaptic compartments is an essential aspect of their neurological function. Current methodology such as electron microscopy (EM) and super-resolution imaging techniques can provide precise localization of proteins, but are often limited to a small number of one-time observations with narrow spatial and molecular coverage. The diversity of synaptic proteins and synapse types demands synapse analysis on a scale that is prohibitive with current methods. Here, we demonstrate SubSynMAP, a fast, multiplexed sub-synaptic protein analysis method using wide-field data from deconvolution array tomography (ATD)...
October 22, 2016: ELife
William R Pitchers, Savvas J Constantinou, Mauricio Losilla, Jason R Gallant
Electric fish have served as a model system in biology since the 18th century, providing deep insight into the nature of bioelectrogenesis, the molecular structure of the synapse, and brain circuitry underlying complex behavior. Neuroethologists have collected extensive phenotypic data that span biological levels of analysis from molecules to ecosystems. This phenotypic data, together with genomic resources obtained over the past decades, have motivated new and exciting hypotheses that position the weakly electric fish model to address fundamental 21(st) century biological questions...
October 18, 2016: Journal of Physiology, Paris
Annekathrin Widmann, Marc Artinger, Lukas Biesinger, Kathrin Boepple, Christina Peters, Jana Schlechter, Mareike Selcho, Andreas S Thum
Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes-besides other forms-a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches...
October 2016: PLoS Genetics
Qian Cai, Prasad Tammineni
Alzheimer's disease (AD) is characterized by brain deposition of amyloid plaques and tau neurofibrillary tangles along with steady cognitive decline. Synaptic damage, an early pathological event, correlates strongly with cognitive deficits and memory loss. Mitochondria are essential organelles for synaptic function. Neurons utilize specialized mechanisms to drive mitochondrial trafficking to synapses in which mitochondria buffer Ca2+ and serve as local energy sources by supplying ATP to sustain neurotransmitter release...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Carles Bosch, Albert Martínez, Nuria Masachs, Cátia M Teixeira, Isabel Fernaud, Fausto Ulloa, Esther Pérez-Martínez, Carlos Lois, Joan X Comella, Javier DeFelipe, Angel Merchán-Pérez, Eduardo Soriano
[This corrects the article on p. 60 in vol. 9, PMID: 26052271.].
2016: Frontiers in Neuroanatomy
Christoph T Schanzenbächer, Sivakumar Sambandan, Julian D Langer, Erin M Schuman
Homeostatic scaling adjusts the strength of synaptic connections up or down in response to large changes in input. To identify the landscape of proteomic changes that contribute to opposing forms of homeostatic plasticity, we examined the plasticity-induced changes in the newly synthesized proteome. Cultured rat hippocampal neurons underwent homeostatic up-scaling or down-scaling. We used BONCAT (bio-orthogonal non-canonical amino acid tagging) to metabolically label, capture, and identify newly synthesized proteins, detecting and analyzing 5,940 newly synthesized proteins using mass spectrometry and label-free quantitation...
October 19, 2016: Neuron
Sergio Valbuena, Juan Lerma
Neurotransmitter receptors are responsible for the transfer of information across the synapse. While ionotropic receptors form ion channels and mediate rapid membrane depolarization, so-called metabotropic receptors exert their action though slower, less direct intracellular signaling pathways. Glutamate, GABA, and acetylcholine can activate both ionotropic and metabotropic receptors, yet the distinction between these "canonical" signaling systems has become less clear since ionotropic receptors were proposed to also activate second messenger systems, defining a "non-canonical" signaling pathway...
October 19, 2016: Neuron
Jessica M Meves, Binhai Zheng
In this issue of Neuron, Tedeschi et al. (2016) describe the voltage-gated calcium channel subunit alpha2delta2 as a developmental switch from axon elongation to synapse formation and transmission that doubles as a suppressor of axon regeneration, providing a molecular clue for the synaptic stabilization hypothesis of CNS regeneration failure.
October 19, 2016: Neuron
Laiyuan Wang, Zhiyong Wang, Jinyi Lin, Jie Yang, Linghai Xie, Mingdong Yi, Wen Li, Haifeng Ling, Changjin Ou, Wei Huang
Most simulations of neuroplasticity in memristors, which are potentially used to develop artificial synapses, are confined to the basic biological Hebbian rules. However, the simplex rules potentially can induce excessive excitation/inhibition, even collapse of neural activities, because they neglect the properties of long-term homeostasis involved in the frameworks of realistic neural networks. Here, we develop organic CuPc-based memristors of which excitatory and inhibitory conductivities can implement both Hebbian rules and homeostatic plasticity, complementary to Hebbian patterns and conductive to the long-term homeostasis...
October 20, 2016: Scientific Reports
Mahar Fatima, Bharat Prajapati, Kanza Saleem, Rina Kumari, Chitra Mohindar Singh Singal, Pankaj Seth
Astroglia are indispensable component of the tripartite synapse ensheathing innumerous soma and synapses. Its proximity to neurons aids the regulation of neuronal functions, health and survival through dynamic neuroglia crosstalk. Susceptibility of astrocyte to HIV-1 infection and subsequent latency culminates in compromised neuronal health. The viral protein HIV-1 transactivator of transcription (Tat) is neurotoxic. HIV-1 Tat is detected in brain of AIDS patients even in cases where viral load is non-detectable due to successful HAART therapy...
October 20, 2016: Glia
Maksim Storozhuk, Elena Kondratskaya, Lyudmila Nikolaenko, Oleg Krishtal
Rapid acidification occurring during synaptic vesicle release can activate acid-sensing ion channels (ASICs) both on pre- and postsynaptic neurons. In the latter case, a fraction of postsynaptic current would be mediated by cation-selective acid-sensing ion channels. Additionally, in both cases, activation of acid-sensing ion channels could modulate synaptic strength by affecting transmitter release and/or sensitivity of postsynaptic receptors. To address potential involvement of acid-sensing ion channels in mediation/modulation of synaptic transmission at hippocampal GABAergic synapses, we studied effects of three structurally different blockers of acid-sensing ion channels on evoked postsynaptic currents using the patch-clamp technique...
October 19, 2016: Molecular Brain
Jeroen Aerts, Annelies Laeremans, Laurens Minerva, Kurt Boonen, Budamgunta Harshavardhan, Rudi D'hooge, Dirk Valkenborg, Geert Baggerman, Lutgarde Arckens
The Morris water maze (MWM) spatial learning task has been demonstrated to involve a cognitive switch of action control to serve the transition from an early towards a late learning phase. However, the molecular mechanisms governing this switch are largely unknown. We employed MALDI MS imaging (MSI) to screen for changes in expression of small proteins in brain structures implicated in the different learning phases. We compared mice trained for 3days and 30days in the MWM, reflecting an early and a late learning phase in relation to the acquisition of a spatial learning task...
October 17, 2016: Biochimica et Biophysica Acta
Jeffrey T Ehmsen, Yong Liu, Yue Wang, Nikhil Paladugu, Anna E Johnson, Jeffrey D Rothstein, Sascha du Lac, Mark P Mattson, Ahmet Höke
SLC7A10 (Asc-1) is a sodium-independent amino acid transporter known to facilitate transport of a number of amino acids including glycine, L-serine, L-alanine, and L-cysteine, as well as their D-enantiomers. It has been described as a neuronal transporter with a primary role related to modulation of excitatory glutamatergic neurotransmission. We find that SLC7A10 is substantially enriched in a subset of astrocytes of the caudal brain and spinal cord in a distribution corresponding with high densities of glycinergic inhibitory synapses...
October 19, 2016: Scientific Reports
Eva Maria Putz, Andrea Majoros, Dagmar Gotthardt, Michaela Prchal-Murphy, Eva Maria Zebedin-Brandl, Daniela Alexandra Fux, Andreas Schlattl, Robert D Schreiber, Sebastian Carotta, Mathias Müller, Christopher Gerner, Thomas Decker, Veronika Sexl
STAT1 is an important regulator of NK cell maturation and cytotoxicity. Although the consequences of Stat1-deficiency have been described in detail the underlying molecular functions of STAT1 in NK cells are only partially understood. Here, we describe a novel non-canonical role of STAT1 that was unmasked in NK cells expressing a Stat1-Y701F mutant. This mutation prevents JAK-dependent phosphorylation, subsequent nuclear translocation and cytokine-induced transcriptional activity as verified by RNA-seq analysis...
2016: Oncoimmunology
Nils Rademacher, Bettina Schmerl, Jennifer A Lardong, Markus C Wahl, Sarah A Shoichet
At neuronal synapses, multiprotein complexes of trans-synaptic adhesion molecules, scaffold proteins and neurotransmitter receptors assemble to essential building blocks required for synapse formation and maintenance. Here we describe a novel role for the membrane-associated guanylate kinase (MAGUK) protein MPP2 (MAGUK p55 subfamily member 2) at synapses of rat central neurons. Through interactions mediated by its C-terminal SH3-GK domain module, MPP2 binds to the abundant postsynaptic scaffold proteins PSD-95 and GKAP and localises to postsynaptic sites in hippocampal neurons...
October 19, 2016: Scientific Reports
Meagan E Ita, Nathan D Crosby, Ben A Bulka, Beth A Winkelstein
STUDY DESIGN: Immunohistochemistry labeled pre- and post-synaptic structural markers to quantify excitatory and inhibitory synapses in the spinal superficial dorsal horn at 14 days after painful facet joint injury in the rat. OBJECTIVE: The objective of this study was to investigate the relationship between pain and synapse density in the spinal cord after facet injury. SUMMARY OF BACKGROUND DATA: Neck pain is a major contributor to disability and often becomes chronic...
October 17, 2016: Spine
Kei Ando, Shiro Imagama, Zenya Ito, Kazuyoshi Kobayashi, Tetsuro Hida, Hiroaki Nakashima, Kenyu Ito, Mikito Tsushima, Yoshimoto Ishikawa, Akiyuki Matsumoto, Koji Nishida, Yoshihiro Nishida, Naoki Ishiguro
STUDY DESIGN: Self-assembling peptide gel (SPG-178) provides new evidence for the role of a scaffold for treatment of the spinal cord through induction of neuroprotective factors. OBJECTIVE: To verify the reproducibility of SPG-178 as scaffold after spinal cord injury, we examine the characteristics of SPG-178 and protective effect on neural cells in vitro and in vivo. SUMMARY OF BACKGROUND DATA: The central nervous system extracellular matrix may play a role in maintenance of the neuronal network by inhibiting axonal growth and suppressing formation of additional inadequate synapses...
October 15, 2016: Spine
Miguel Hernández-Cerón, Juan Carlos Martínez-Lazcano, Carmen Rubio, Verónica Custodio, Edith González-Guevara, Carlos Castillo-Pérez, Carlos Paz
Lesions of the cerebellar dentate nucleus (DN) reduce the after-discharge duration induced by repetitive kindling stimulation and decrease seizures to a lower rank according to Racine's scale. The DN sends cholinergic and glutamatergic fibers to the red nucleus (RN), which is composed of glutamatergic and GABAergic cells. To test the participation of these neurotransmitters in seizures, we compared the levels of glutamate and gamma-aminobutyric acid (GABA) at the RN in a control condition, a kindled stage, and a kindled stage followed by DN lesions...
October 18, 2016: Journal of Neuroscience Research
George S Vidal, Maja Djurisic, Kiana Brown, Richard W Sapp, Carla J Shatz
Synapse density on cortical pyramidal neurons is modulated by experience. This process is highest during developmental critical periods, when mechanisms of synaptic plasticity are fully engaged. In mouse visual cortex, the critical period for ocular dominance (OD) plasticity coincides with the developmental pruning of synapses. At this time, mice lacking paired Ig-like receptor B (PirB) have excess numbers of dendritic spines on L5 neurons; these spines persist and are thought to underlie the juvenile-like OD plasticity observed in adulthood...
September 2016: ENeuro
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