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Synapse formation

Angela M Getz, Pierre Wijdenes, Saba Riaz, Naweed I Syed
All functions of the nervous system are contingent upon the precise organization of neuronal connections that are initially patterned during development, and then continually modified throughout life. Determining the mechanisms that specify the formation and functional modulation of synaptic circuitry are critical to advancing both our fundamental understanding of the nervous system as well as the various neurodevelopmental, neurological, neuropsychiatric, and neurodegenerative disorders that are met in clinical practice when these processes go awry...
March 12, 2018: ACS Chemical Neuroscience
Kenji Hanamura, Yousuke Kamata, Hiroyuki Yamazaki, Nobuhiko Kojima, Tomoaki Shirao
Dendritic spines have stable filamentous actin (F-actin) and dynamic F-actin. The formation of stable F-actin plays a pivotal role in spine formation. Drebrin binds to and stabilizes F-actin in dendritic spines. Interestingly, the conversion of the drebrin E isoform to drebrin A occurs in parallel with synapse formation, suggesting that this conversion promotes synapse formation via F-actin accumulation. In this study, we measured the dynamics of GFP-tagged drebrin E (GFP-DE) and drebrin A (GFP-DA) in cultured hippocampal neurons by fluorescence recovery after photobleaching analysis...
March 6, 2018: Neuroscience
Lifu Sheng, Iryna Leshchyns'ka, Vladimir Sytnyk
The neural cell adhesion molecule 2 (NCAM2) is encoded by a gene on chromosome 21 in humans. NCAM2 accumulates in synapses, but its role in regulation of synapse formation remains poorly understood. We demonstrate that an increase in NCAM2 levels results in increased instability of dendritic protrusions and reduced conversion of protrusions to dendritic spines in mouse cortical neurons. NCAM2 overexpression induces an increase in the frequency of submembrane Ca2+ spikes localized in individual dendritic protrusions and promotes propagation of submembrane Ca2+ spikes over segments of dendrites or the whole dendritic tree...
March 7, 2018: Cerebral Cortex
Lucie Bracq, Maorong Xie, Serge Benichou, Jérôme Bouchet
While HIV-1 infection of target cells with cell-free viral particles has been largely documented, intercellular transmission through direct cell-to-cell contact may be a predominant mode of propagation in host. To spread, HIV-1 infects cells of the immune system and takes advantage of their specific particularities and functions. Subversion of intercellular communication allows to improve HIV-1 replication through a multiplicity of intercellular structures and membrane protrusions, like tunneling nanotubes, filopodia, or lamellipodia-like structures involved in the formation of the virological synapse...
2018: Frontiers in Immunology
Mehdi Borjkhani, Fariba Bahrami, Mahyar Janahmadi
According to a broad range of research, opioids consumption can lead to pathological memory formation. Experimental observations suggested that hippocampal glutamatergic synapses play an indispensable role in forming such a pathological memory. It has been suggested that memory formation at the synaptic level is developed through LTP induction. Here, we attempt to computationally indicate how morphine induces pathological LTP at hippocampal CA3-CA1 synapses. Then, based on simulations, we will suggest how one can prevent this type of pathological LTP...
2018: PloS One
Zhifeng Wang, Zhouqing Chen, Junjie Yang, Ziying Yang, Jia Yin, Xiaochun Duan, Haitao Shen, Haiying Li, Zhong Wang, Gang Chen
Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1-neuroligin-1 to form a complex and participates in maintaining synaptic function...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Hideji Murakoshi
In the past decade, the various types of genetically-encoded optogenetic tools using blue-light sensitive LOV2 domain have been developed and applied in a wide range of areas including neuroscience field. Recently, we succeeded in developing a photoactivatable inhibitory peptide, a genetically-encoded light inducible CaMKⅡ inhibitory peptide. Using this new optogenetic tool, we found that the 1 min of CaMKⅡ activation is sufficient for triggering structural plasticity of synapses(spines)in hippocampal neurons...
2018: Clinical Calcium
Ryo Ueta, Yuji Yamanashi
The neuromuscular junction(NMJ)is the synapse between a motor neuron and the skeletal muscle that is essential for muscle contraction. Impairments at the NMJ lead to neuromuscular-transmission pathologies characterized by fatigable muscle weakness. Muscle-specific receptor tyrosine kinase MuSK plays key roles in NMJ formation. Over the past decade, studies examining the NMJ formation signals have identified molecules involved in the signaling pathways and have promoted a better understanding of characteristic molecular mechanisms for MuSK activation...
2018: Clinical Calcium
Alain Calender, Pierre Antoine Rollat Farnier, Adrien Buisson, Stéphane Pinson, Abderrazzaq Bentaher, Serge Lebecque, Harriet Corvol, Rola Abou Taam, Véronique Houdouin, Claire Bardel, Pascal Roy, Gilles Devouassoux, Vincent Cottin, Pascal Seve, Jean-François Bernaudin, Clarice X Lim, Thomas Weichhart, Dominique Valeyre, Yves Pacheco, Annick Clement, Nadia Nathan
BACKGROUND: Sarcoidosis (OMIM 181000) is a multi-systemic granulomatous disorder of unknown origin. Despite multiple genome-wide association (GWAS) studies, no major pathogenic pathways have been identified to date. To find out relevant sarcoidosis predisposing genes, we searched for de novo and recessive mutations in 3 young probands with sarcoidosis and their healthy parents using a whole-exome sequencing (WES) methodology. METHODS: From the SARCFAM project based on a national network collecting familial cases of sarcoidosis, we selected three families (trios) in which a child, despite healthy parents, develop the disease before age 15 yr...
March 6, 2018: BMC Medical Genomics
Carlos Del Rio-Bermudez, Mark S Blumberg
A ubiquitous feature of active (REM) sleep in mammals and birds is its relative abundance in early development. In rat pups across the first two postnatal weeks, active sleep promotes the expression of synchronized oscillatory activity within and between cortical and subcortical sensorimotor structures. Sensory feedback from self-generated myoclonic twitches - which are produced exclusively during active sleep - also triggers neural oscillations in those structures. We have proposed that one of the functions of active sleep in early infancy is to provide a context for synchronizing developing structures...
March 6, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
I A Kuznetsov, A V Kuznetsov
We develop a mathematical model that enables us to investigate possible mechanisms by which two primary markers of Alzheimer's disease (AD), extracellular amyloid plaques and intracellular tangles, may be related. Our model investigates the possibility that the decay of anterograde axonal transport of amyloid precursor protein (APP), caused by toxic tau aggregates, leads to decreased APP transport towards the synapse and APP accumulation in the soma. The developed model thus couples three processes: (i) slow axonal transport of tau, (ii) tau misfolding and agglomeration, which we simulated by using the Finke-Watzky model and (iii) fast axonal transport of APP...
February 2018: Proceedings. Mathematical, Physical, and Engineering Sciences
Shogo Tanabe, Toshihide Yamashita
During brain development, the immune system mediates neurogenesis, gliogenesis and synapse formation. However, it remains unclear whether peripheral lymphocytes contribute to brain development. Here we identified the subtypes of lymphocytes that are present in neonatal mouse brains and investigated their functions. We found that B-1a cells, a subtype of B cells, were abundant in the neonatal mouse brain and infiltrated into the brain in a CXCL13-CXCR5-dependent manner. B-1a cells promoted the proliferation of oligodendrocyte-precursor cells (OPCs) in vitro, and depletion of B-1a cells from developing brains resulted in a reduction of numbers of OPCs and mature oligodendrocytes...
March 5, 2018: Nature Neuroscience
Wei Cao, Shen Lin, Qiang-Qiang Xia, Yong-Lan Du, Qian Yang, Meng-Ying Zhang, Yi-Qing Lu, Jing Xu, Shu-Min Duan, Xia Jun, Guoping Feng, Junyu Xu, Jian-Hong Luo
Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice...
February 22, 2018: Neuron
Satoshi Iraha, Hung-Ya Tu, Suguru Yamasaki, Takahiro Kagawa, Motohito Goto, Riichi Takahashi, Takehito Watanabe, Sunao Sugita, Shigenobu Yonemura, Genshiro A Sunagawa, Take Matsuyama, Momo Fujii, Atsushi Kuwahara, Akiyoshi Kishino, Naoshi Koide, Mototsugu Eiraku, Hidenobu Tanihara, Masayo Takahashi, Michiko Mandai
Increasing demand for clinical retinal degeneration therapies featuring human ESC/iPSC-derived retinal tissue and cells warrants proof-of-concept studies. Here, we established two mouse models of end-stage retinal degeneration with immunodeficiency, NOG-rd1-2J and NOG-rd10, and characterized disease progress and immunodeficient status. We also transplanted human ESC-derived retinal sheets into NOG-rd1-2J and confirmed their long-term survival and maturation of the structured graft photoreceptor layer, without rejection or tumorigenesis...
February 23, 2018: Stem Cell Reports
Steven M Wellman, Takashi D Y Kozai
Neural interface technology provides direct sampling and analysis of electrical and chemical events in the brain in order to better understand neuronal function and treat neurodegenerative disease. However, intracortical electrodes experience inflammatory reactions that reduce long-term stability and functionality and are understood to be facilitated by activated microglia and astrocytes. Emerging studies have identified another cell type that participates in the formation of a high-impedance glial scar following brain injury; the oligodendrocyte precursor cell (OPC)...
February 20, 2018: Biomaterials
Amal A Halawa, Joanne C Damborsky, G Simona Slaton, Ursula H Winzer-Serhan
Maternal smoking has negative long-term consequences on affective behaviors, and in rodents, chronic neonatal nicotine exposure (CNN) results in increased anxiety. In rat pups, acute nicotine stimulation activates brain regions associated with stress and anxiety, but chronic nicotine exposure could desensitize of nicotinic acetylcholine receptors, the molecular target of nicotine. Here, we determined whether CNN affected neuronal activation by an acute nicotine challenge. Using in situ hybridization, we analyzed mRNA expression of the immediate-early genes (IEGs) c-Fos, Arc, Egr-1 and Npas4, which are markers for neuronal activation and implicated in synaptic plasticity...
February 26, 2018: Brain Research
Stephanie Zur Nedden, Rafaela Eith, Christoph Schwarzer, Lucia Zanetti, Hartwig Seitter, Friedrich Fresser, Alexandra Koschak, Angus Jm Cameron, Peter J Parker, Gottfried Baier, Gabriele Baier-Bitterlich
Increasing evidence suggests that synapse dysfunctions are a major determinant of several neurodevelopmental and neurodegenerative diseases. Here we identify protein kinase N1 (PKN1) as a novel key player in fine-tuning the balance between axonal outgrowth and presynaptic differentiation in the parallel fiber (PF)-forming cerebellar granule cells (Cgc). Postnatal Pkn1-/- animals showed a defective PF-Purkinje cell (PC) synapse formation. In vitro, Pkn1-/- Cgc exhibited deregulated axonal outgrowth, elevated AKT phosphorylation and higher levels of neuronal differentiation-2 (NeuroD2), a transcription factor preventing presynaptic maturation...
March 1, 2018: Journal of Clinical Investigation
Ana Cicvaric, Jiaye Yang, Tanja Bulat, Alice Zambon, Manuel Dominguez-Rodriguez, Rebekka Kühn, Michael G Sadowicz, Anjana Siwert, Joaquim Egea, Daniela D Pollak, Thomas Moeslinger, Francisco J Monje
The Fibronectin Leucine-Rich Transmembrane protein 2 (FLRT2) has been implicated in several hormone -and sex-dependent physiological and pathological processes (including chondrogenesis, menarche and breast cancer); is known to regulate developmental synapses formation, and is expressed in the hippocampus, a brain structure central for learning and memory. However, the role of FLRT2 in the adult hippocampus and its relevance in sex-dependent brain functions remains unknown. We here used adult single-allele FLRT2 knockout (FLRT2+/- ) mice and behavioral, electrophysiological, and molecular/biological assays to examine the effects of FLRT2 haplodeficiency on synaptic plasticity and hippocampus-dependent learning and memory...
February 27, 2018: Scientific Reports
Jasmin Segelken, Melanie Wallisch, Konrad Schultz, Jens Christoffers, Ulrike Janssen-Bienhold
The vitamin A derivative all-trans-retinoic acid (ATRA) is an important biologically active metabolite that regulates a variety of essential biological processes in particular via gene-regulatory mechanisms. In the retina, ATRA is a light-dependent byproduct of the phototransduction cascade. Here, ATRA is not only needed for proper retinal development, but it also acts as a neuromodulator on horizontal cells, second-order inhibitory neurons in the outer retina, which reveal morphological and physiological changes when the retina is treated with ATRA...
February 26, 2018: ACS Chemical Neuroscience
Takamitsu Sano, Ayako Kohyama-Koganeya, Masami O Kinoshita, Tetsuya Tatsukawa, Chika Shimizu, Eriko Oshima, Kazuyuki Yamada, Tung Dinh Le, Takumi Akagi, Koujiro Tohyama, Soichi Nagao, Yoshio Hirabayashi
GPRC5B is a membrane glycoprotein robustly expressed in mouse cerebellar Purkinje cells (PCs). Its function is unknown. In Gprc5b-/- mice that lack GPRC5B, PCs develop distal axonal swellings in deep cerebellar nuclei (DCN). Numerous misshapen mitochondria, which generated excessive amounts of reactive oxygen species (ROS), accumulated in these distal axonal swellings. In primary cell cultures of Gprc5b-/- PCs, pharmacological reduction of ROS prevented the appearance of such swellings. To examine the physiological role of GPRC5B in PCs, we analyzed cerebellar synaptic transmission and cerebellum-dependent motor learning in Gprc5b-/- mice...
February 23, 2018: Neuroscience Research
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