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https://www.readbyqxmd.com/read/28100586/axon-termination-pruning-and-synaptogenesis-in-the-giant-fiber-system-of-drosophila-melanogaster-is-promoted-by-highwire
#1
Melissa Borgen, Kimberly Rowland, Jana Boerner, Brandon Lloyd, Aruna Khan, Rod Murphey
The ubiquitin ligase Highwire has a conserved role in synapse formation. Here we show that Highwire coordinates several facets of central synapse formation in the Drosophila melanogaster giant fiber system, including axon termination, axon pruning, and synaptic function. Despite the similarities to the fly neuromuscular junction, the role of Highwire and the underlying signaling pathways are distinct in the fly's giant fiber system. During development, branching of the giant fiber presynaptic terminal occurs and, normally, the transient branches are pruned away...
January 18, 2017: Genetics
https://www.readbyqxmd.com/read/28095309/microglia-under-psychosocial-stressors-along-the-aging-trajectory-consequences-on-neuronal-circuits-behavior-and-brain-diseases
#2
Li Tian, Chin Wai Hui, Kanchan Bisht, Yunlong Tan, Kaushik Sharma, Song Chen, Xiangyang Zhang, Marie-Eve Tremblay
Mounting evidence indicates the importance of microglia for proper brain development and function, as well as in complex stress-related neuropsychiatric disorders and cognitive decline along the aging trajectory. Considering that microglia are resident immune cells of the brain, a homeostatic maintenance of their effector functions that impact neuronal circuitry, such as phagocytosis and secretion of inflammatory factors, is critical to prevent the onset and progression of these pathological conditions. However, the molecular mechanisms by which microglial functions can be properly regulated under healthy and pathological conditions are still largely unknown...
January 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28093559/gradation-approx-10-size-states-of-synaptic-strength-by-quantal-addition-of-structural-modules
#3
Kang K L Liu, Michael F Hagan, John E Lisman
Memory storage involves activity-dependent strengthening of synaptic transmission, a process termed long-term potentiation (LTP). The late phase of LTP is thought to encode long-term memory and involves structural processes that enlarge the synapse. Hence, understanding how synapse size is graded provides fundamental information about the information storage capability of synapses. Recent work using electron microscopy (EM) to quantify synapse dimensions has suggested that synapses may structurally encode as many as 26 functionally distinct states, which correspond to a series of proportionally spaced synapse sizes...
March 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28093558/glutamatergic-synapses-are-structurally-and-biochemically-complex-because-of-multiple-plasticity-processes-long-term-potentiation-long-term-depression-short-term-potentiation-and-scaling
#4
REVIEW
John Lisman
Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity. Here, I comment on recent developments regarding these processes. (i) Short-term potentiation (STP), a Hebbian process that requires small amounts of synaptic input, appears to make strong contributions to some forms of working memory. (ii) The rules for long-term potentiation (LTP) induction in CA3 have been clarified: induction does not depend obligatorily on backpropagating sodium spikes but, rather, on dendritic branch-specific N-methyl-d-aspartate (NMDA) spikes...
March 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28093479/paired-stimulation-for-spike-timing-dependent-plasticity-in-primate-sensorimotor-cortex
#5
Stephanie C Seeman, Brian J Mogen, Eberhard E Fetz, Steve I Perlmutter
: Classic studies in vitro have described spike-timing dependent plasticity (STDP) at a synapse: the connection from neuron A to neuron B is strengthened (or weakened) when A fires before (or after) B within an optimal time window. Accordingly, more recent in vivo works have demonstrated behavioral effects consistent with an STDP mechanism; however many relied on single-unit recordings. The ability to modify cortical connections becomes useful in the context of injury when connectivity, and associated behavior, is compromised...
January 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28092659/rem-sleep-selectively-prunes-and-maintains-new-synapses-in-development-and-learning
#6
Wei Li, Lei Ma, Guang Yang, Wen-Biao Gan
The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning...
January 16, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28090790/loss-of-interneuron-derived-collagen-xix-leads-to-a-reduction-in-perineuronal-nets-in-the-mammalian-telencephalon
#7
Jianmin Su, James Cole, Michael A Fox
Perineuronal nets (PNNs) are lattice-like supramolecular assemblies of extracellular glycoproteins that surround subsets of neuronal cell bodies in the mammalian telencephalon. PNNs emerge at the end of the critical period of brain development, limit neuronal plasticity in the adult brain, and are lost in a variety of complex brain disorders diseases, including schizophrenia. The link between PNNs and schizophrenia led us to question whether neuronally expressed extracellular matrix (ECM) molecules associated with schizophrenia contribute to the assembly of these specialized supramolecular ECM assemblies...
February 2017: ASN Neuro
https://www.readbyqxmd.com/read/28087765/synapsin-ii-regulation-of-gabaergic-synaptic-transmission-is-dependent-on-interneuron-subtype
#8
Pedro Feliciano, Heidi Matos, Rodrigo Andrade, Maria Bykhovskaia
: Synapsins are epilepsy susceptibility genes that encode phosphoproteins reversibly associated with synaptic vesicles. Synapsin II (SynII) gene deletion produces a deficit in inhibitory synaptic transmission, and this defect is thought to cause epileptic activity. We systematically investigated how SynII affects synchronous and asynchronous release components of inhibitory transmission in the CA1 region of the mouse hippocampus. We found that the asynchronous GABAergic release component is diminished in SynII deleted (SynII(-)) slices...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28081563/interactions-with-astroglia-influence-the-shape-of-the-developing-dendritic-arbor-and-restrict-dendrite-growth-independent-of-promoting-synaptic-contacts
#9
Ginger S Withers, Jennifer R Farley, Jeffrey R Sterritt, Andrés B Crane, Christopher S Wallace
Astroglia play key roles in the development of neurons, ranging from regulating neuron survival to promoting synapse formation, yet basic questions remain about whether astrocytes might be involved in forming the dendritic arbor. Here, we used cultured hippocampal neurons as a simple in vitro model that allowed dendritic growth and geometry to be analyzed quantitatively under conditions where the extent of interactions between neurons and astrocytes varied. When astroglia were proximal to neurons, dendrites and dendritic filopodia oriented toward them, but the general presence of astroglia significantly reduced overall dendrite growth...
2017: PloS One
https://www.readbyqxmd.com/read/28077712/changes-in-properties-of-auditory-nerve-synapses-following-conductive-hearing-loss
#10
Xiaowen Zhuang, Wei Sun, Matthew A Xu-Friedman
: Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077511/altered-connectivity-and-synapse-maturation-of-the-hippocampal-mossy-fiber-pathway-in-a-mouse-model-of-the-fragile-x-syndrome
#11
F Scharkowski, Michael Frotscher, David Lutz, Martin Korte, Kristin Michaelsen-Preusse
The Fragile X syndrome (FXS) as the most common monogenetic cause of cognitive impairment and autism indicates how tightly the dysregulation of synapse development is linked to cognitive deficits. Symptoms of FXS include excessive adherence to patterns that point to compromised hippocampal network formation. Surprisingly, one of the most complex hippocampal synapses connecting the dentate gyrus (DG) to CA3 pyramidal neurons has not been analyzed in FXS yet. Intriguingly, we found altered synaptic function between DG and CA3 in a mouse model of FXS (fmr1 knockout [KO]) demonstrated by increased mossy fiber-dependent miniature excitatory postsynaptic current (mEPSC) frequency at CA3 pyramidal neurons together with increased connectivity between granule cells and CA3 neurons...
January 10, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28074469/development-of-cone-photoreceptors-and-their-synapses-in-the-human-and-monkey-fovea
#12
Anita Hendrickson, Chi Zhang
During retinal development, ribbon synapse assembly in the photoreceptors is a crucial step involving numerous molecules. While the developmental sequence of plexiform layers in human retina has been characterized, the molecular steps of synaptogenesis remain largely unknown. In the present study, we focused on the central rod-free region of primate retina, the fovea, to specifically investigate the development of cone photoreceptor ribbon synapses. Immunocytochemistry and electron microscopy were utilized to track the expression of photoreceptor transduction proteins and ribbon and synaptic markers in fetal human and Macaca retina...
January 11, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28070120/the-protocadherin-17-gene-affects-cognition-personality-amygdala-structure-and-function-synapse-development-and-risk-of-major-mood-disorders
#13
H Chang, N Hoshina, C Zhang, Y Ma, H Cao, Y Wang, D-D Wu, S E Bergen, M Landén, C M Hultman, M Preisig, Z Kutalik, E Castelao, M Grigoroiu-Serbanescu, A J Forstner, J Strohmaier, J Hecker, T G Schulze, B Müller-Myhsok, A Reif, P B Mitchell, N G Martin, P R Schofield, S Cichon, M M Nöthen, H Walter, S Erk, A Heinz, N Amin, C M van Duijn, A Meyer-Lindenberg, H Tost, X Xiao, T Yamamoto, M Rietschel, M Li
Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers...
January 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28069928/functional-organization-of-cutaneous-and-muscle-afferent-synapses-onto-immature-spinal-lamina-i-projection-neurons
#14
Jie Li, Mark L Baccei
: It is well-established that sensory afferents innervating muscle are more effective at inducing hyperexcitability within spinal cord circuits compared to skin afferents, which likely contributes to the higher prevalence of chronic musculoskeletal pain compared to pain of cutaneous origin. However, the mechanisms underlying these differences in central nociceptive signaling remain incompletely understood, as nothing is known about how superficial dorsal horn (SDH) neurons process sensory input from muscle vs...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069376/translational-issues-in-cochlear-synaptopathy
#15
REVIEW
Ann E Hickox, Erik Larsen, Michael G Heinz, Leslie Shinobu, Jonathon P Whitton
Understanding the biology of the previously underappreciated sensitivity of cochlear synapses to noise insult, and its clinical consequences, is becoming a mission for a growing number of auditory researchers. In addition, several research groups have become interested in developing therapeutic approaches that can reverse synaptopathy and restore hearing function. One of the major challenges to realizing the potential of synaptopathy rodent models is that current clinical audiometric approaches cannot yet reveal the presence of this subtle cochlear pathology in humans...
January 6, 2017: Hearing Research
https://www.readbyqxmd.com/read/28067771/ck2-an-emerging-target-for-neurological-and-psychiatric-disorders
#16
REVIEW
Julia Castello, Andre Ragnauth, Eitan Friedman, Heike Rebholz
Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses...
January 5, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28067280/increase-in-%C3%AE-tubulin-modifications-in-the-neuronal-processes-of-hippocampal-neurons-in-both-kainic-acid-induced-epileptic-seizure-and-alzheimer-s-disease
#17
Hang Thi Vu, Hiroyasu Akatsu, Yoshio Hashizume, Mitsutoshi Setou, Koji Ikegami
Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28067168/sumoylation-in-neurological-diseases
#18
F-Y Liu, Y-F Liu, Y Yang, Z-W Luo, J-W Xiang, Z-G Chen, R-L Qi, T-H Yang, Y Xiao, W-J Qing, D W-C Li
Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important post-translational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases...
January 9, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28064424/gender-related-hippocampal-proteomics-study-from-young-rats-after-chronic-unpredicted-mild-stress-exposure
#19
Lin-Na Ning, Teng Zhang, Jiang Chu, Na Qu, Li Lin, Ying-Yan Fang, Yan Shi, Peng Zeng, Er-Li Cai, Xiao-Ming Wang, Qun Wang, You-Ming Lu, Xin-Wen Zhou, Qi Zhang, Qing Tian
Clinical data have shown women are more susceptible to depression. This study was performed to identify differentially regulated proteins from hippocampus in chronic unpredicted mild stress (CUMS)-exposed male and female young rats. After 7 weeks of CUMS, depressed male (M-D) and female rats (F-D) and unstressed male (M-C) and female controls (F-C) were studied. By proteomics analysis, 74 differential proteins in F-C/M-C, 79 in F-D/M-D, 77 in F-D/F-C, and 32 in M-D/M-C were found. Further, the synapse-related proteins, cytoskeleton protein tau, and stress-related kinases in hippocampus were assayed by Western blotting...
January 7, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28059794/oxidative-stress-synaptic-dysfunction-and%C3%A2-alzheimer-s-disease
#20
Eric Tönnies, Eugenia Trushina
Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding of the disease mechanism hinders the development of efficacious therapeutic approaches. The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss. Oxidative stress has been recognized as a contributing factor in aging and in the progression of multiple neurodegenerative diseases including AD...
December 3, 2017: Journal of Alzheimer's Disease: JAD
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