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Synapse formation

Matthew J Gazzellone, Mehdi Zarrei, Christie L Burton, Susan Walker, Mohammed Uddin, S M Shaheen, Julie Coste, Rageen Rajendram, Reva J Schachter, Marlena Colasanto, Gregory L Hanna, David R Rosenberg, Noam Soreni, Kate D Fitzgerald, Christian R Marshall, Janet A Buchanan, Daniele Merico, Paul D Arnold, Stephen W Scherer
BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. METHODS: We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0...
2016: Journal of Neurodevelopmental Disorders
Christine Gross, Veit Wiesmann, Sebastian Millen, Martina Kalmer, Thomas Wittenberg, Jan Gettemans, Andrea K Thoma-Kress
The delta-retrovirus Human T-cell leukemia virus type 1 (HTLV-1) preferentially infects CD4+ T-cells via cell-to-cell transmission. Viruses are transmitted by polarized budding and by transfer of viral biofilms at the virological synapse (VS). Formation of the VS requires the viral Tax protein and polarization of the host cytoskeleton, however, molecular mechanisms of HTLV-1 cell-to-cell transmission remain incompletely understood. Recently, we could show Tax-dependent upregulation of the actin-bundling protein Fascin (FSCN-1) in HTLV-1-infected T-cells...
October 2016: PLoS Pathogens
Seung-Hee Lee, Jaehoon Shim, Ye-Hwang Cheong, Sun-Lim Choi, Yong-Woo Jun, Sue-Hyun Lee, Yeon-Su Chae, Jin-Hee Han, Yong-Seok Lee, Jin-A Lee, Chae-Seok Lim, Kausik Si, Stefan Kassabov, Igor Antonov, Eric R Kandel, Bong-Kiun Kaang, Deok-Jin Jang
Two pharmacologically distinct types of local protein synthesis are required for synapse- specific long-term synaptic facilitation (LTF) in Aplysia: one for initiation and the other for maintenance. ApCPEB, a rapamycin sensitive prion-like molecule regulates a form of local protein synthesis that is specifically required for the maintenance of the LTF. However, the molecular component of the local protein synthesis that is required for the initiation of LTF and that is sensitive to emetine is not known. Here, we identify a homolog of ApCPEB responsible for the initiation of LTF...
October 22, 2016: Molecular Brain
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
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
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
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
Anthony Holtmaat, Pico Caroni
Learning and memory are associated with the formation and modification of neuronal assemblies: populations of neurons that encode what has been learned and mediate memory retrieval upon recall. Functional studies of neuronal assemblies have progressed dramatically thanks to recent technological advances. Here we discuss how a focus on assembly formation and consolidation has provided a powerful conceptual framework to relate mechanistic studies of synaptic and circuit plasticity to behaviorally relevant aspects of learning and memory...
October 17, 2016: Nature Neuroscience
Miguel A Gonzalez-Lozano, Patricia Klemmer, Titia Gebuis, Chopie Hassan, Pim van Nierop, Ronald E van Kesteren, August B Smit, Ka Wan Li
Development of the brain involves the formation and maturation of numerous synapses. This process requires prominent changes of the synaptic proteome and potentially involves thousands of different proteins at every synapse. To date the proteome analysis of synapse development has been studied sparsely. Here, we analyzed the cortical synaptic membrane proteome of juvenile postnatal days 9 (P9), P15, P21, P27, adolescent (P35) and different adult ages P70, P140 and P280 of C57Bl6/J mice. Using a quantitative proteomics workflow we quantified 1560 proteins of which 696 showed statistically significant differences over time...
October 17, 2016: Scientific Reports
Minhan Ka, Yeon-Hee Kook, Ke Liao, Shilpa Buch, Woo-Yang Kim
Cocaine is a highly addictive narcotic associated with dendritic spine plasticity in the striatum. However, it remains elusive whether cocaine modifies spines in a cell type-specific or region-specific manner or whether it alters different types of synapses in the brain. In addition, there is a paucity of data on the regulatory mechanism(s) involved in cocaine-induced modification of spine density. In the current study, we report that cocaine exposure differentially alters spine density, spine morphology, and the types of synapses in hippocampal and cortical neurons...
October 13, 2016: Cell Death & Disease
Paul Strecker, Susann Ludewig, Marco Rust, Tabea A Mundinger, Andreas Görlich, Elisa G Krächan, Christina Mehrfeld, Joachim Herz, Martin Korte, Suzanne Y Guénette, Stefan Kins
The FE65 adaptor proteins (FE65, FE65L1 and FE65L2) bind proteins that function in diverse cellular pathways and are essential for specific biological processes. Mice lacking both FE65 and FE65L1 exhibit ectopic neuronal positioning in the cortex and muscle weakness. p97FE65-KO mice, expressing a shorter FE65 isoform able to bind amyloid precursor protein family members (APP, APLP1, APLP2), develop defective long-term potentiation (LTP) and aged mice display spatial learning and memory deficits that are absent from young mice...
May 11, 2016: Scientific Reports
Thomas I Talpalar, Adolfo E Talpalar
Hyperbaric environments induce the high pressure neurological syndrome (HPNS) characterized by hyperexcitability of the central nervous system (CNS) and memory impairment. Human divers and other animals experience the HPNS at pressures beyond 1.1 MPa. High pressure depresses synaptic transmission and alters its dynamics in various animal models. Medial perforant path (MPP) synapses connecting the medial entorhinal cortex with the hippocampal formation are suppressed by 50% at 10.1MPa. Reduction of synaptic inputs is paradoxically associated with enhanced ability of dentate gyrus (DG)' granule cells (GCs) to generate spikes at high pressure...
2016: Frontiers in Cellular Neuroscience
Indulekha P Sudhakaran, Mani Ramaswami
Long-term and short-term memories differ primarily in the duration of their retention. At a molecular level, long-term memory (LTM) is distinguished from short-term memory (STM) by its requirement for new gene expression. In addition to transcription (nuclear gene expression) the translation of stored mRNAs is necessary for LTM formation. The mechanisms and functions for temporal and spatial regulation of mRNAs required for LTM is a major contemporary problem, of interest from molecular, cell biological, neurobiological and clinical perspectives...
October 11, 2016: RNA Biology
Chiaki Itami, Fumitaka Kimura
Spike timing-dependent plasticity (STDP) has been demonstrated in a variety of neural circuits. Recent studies reveal that it plays a fundamental role in the formation and remodeling of neuronal circuits. We show here an interaction of two distinct forms of STDP in the mouse barrel cortex causing concurrent, plastic changes, potentially a novel mechanism underlying network remodeling. We previously demonstrated that during the second postnatal week, when layer four (L4) cells are forming synapses onto L2/3 cells, L4-L2/3 synapses exhibit STDP with only long-term potentiation (t-LTP)...
October 11, 2016: European Journal of Neuroscience
Agata Mata, Laura Urrea, Silvia Vilches, Franc Llorens, Katrin Thüne, Juan-Carlos Espinosa, Olivier Andréoletti, Alejandro M Sevillano, Juan María Torres, Jesús Rodríguez Requena, Inga Zerr, Isidro Ferrer, Rosalina Gavín, José Antonio Del Río
Reelin is an extracellular glycoprotein involved in key cellular processes in developing and adult nervous system, including regulation of neuronal migration, synapse formation, and plasticity. Most of these roles are mediated by the intracellular phosphorylation of disabled-1 (Dab1), an intracellular adaptor molecule, in turn mediated by binding Reelin to its receptors. Altered expression and glycosylation patterns of Reelin in cerebrospinal and cortical extracts have been reported in Alzheimer's disease...
October 10, 2016: Molecular Neurobiology
Chihiro Tohda
Alzheimer's disease (AD) is a recognized incurable neurodegenerative disorder. Clinically prescribed medicines for AD are expected to bring about only slight symptomatic improvement or a delay of its progression. Another strategy, amyloid β (Aβ) lowing agents, has not been successful at memory improvement. We have hypothesized that an improvement in cognitive function requires the construction of neuronal networks, including neurite regeneration and synapse formation; therefore, we have been exploring candidates for radical anti-AD drugs that can restore Aβ-induced neurite atrophy and memory impairment...
2016: Biological & Pharmaceutical Bulletin
Marco Sassoè-Pognetto, Annarita Patrizi
Since the groundbreaking work of Ramon y Cajal, the cerebellar Purkinje cell has always represented an ideal model for studying the organization, development and function of synaptic circuits. Purkinje cells receive distinct types of glutamatergic and GABAergic synapses, each characterized by exquisite sub-cellular and molecular specificity. The formation and refinement of these connections results from a temporally-regulated sequence of events that involves molecular interactions between distinct sets of secreted and surface proteins, as well as activity-dependent competition between converging inputs...
October 6, 2016: Brain Research Bulletin
Corette J Wierenga
In this review I discuss recent live imaging studies that demonstrate that synapses, and in particular inhibitory synapses, are highly dynamic structures. The ongoing changes of presynaptic boutons within axons emphasize the stochastic aspect of inhibitory synapse formation and paint a picture of a dynamic trial-and-error process. Furthermore, I discuss recent and previous insights in the molecular and mechanistic pathways that underlie synapse formation, with a specific focus on the formation of inhibitory presynaptic boutons...
October 5, 2016: Brain Research Bulletin
M J Skelly, O J Ariwodola, J L Weiner
Inappropriate fear memory formation is symptomatic of many psychopathologies, and delineating the neurobiology of non-pathological fear learning may provide critical insight into treating these disorders. Fear memory formation is associated with decreased inhibitory signaling in the basolateral amygdala (BLA), and disrupted noradrenergic signaling may contribute to this decrease. BLA noradrenergic neurotransmission has been implicated in fear memory formation, and distinct adrenoreceptor (AR) subtypes modulate excitatory and inhibitory neurotransmission in this region...
October 5, 2016: Neuropharmacology
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