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https://www.readbyqxmd.com/read/28433456/cytokine-alterations-and-cognitive-impairment-in-major-depressive-disorder-from-putative-mechanisms-to-novel-treatment-targets
#1
REVIEW
Błażej Misiak, Jan Aleksander Beszłej, Kamila Kotowicz, Monika Szewczuk-Bogusławska, Jerzy Samochowiec, Jolanta Kucharska-Mazur, Dorota Frydecka
Overwhelming evidence indicates the involvement of immune-inflammatory processes in the pathophysiology of major depressive disorder (MDD). Peripheral cytokine alterations serve as one of most consistently reported indices of subthreshold inflammatory state observed in MDD. Although cytokines cannot pass directly through the blood-brain barrier, a number of transport mechanisms have been reported. In addition, peripheral cytokines may impact central nervous system via downstream effectors of their biological activity...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28432787/presynaptic-morphology-and-vesicular-composition-determine-vesicle-dynamics-in-mouse-central-synapses
#2
Laurent Guillaud, Dimitar Dimitrov, Tomoyuki Takahashi
Transport of synaptic vesicles (SVs) in nerve terminals is thought to play essential roles in maintenance of neurotransmission. To identify factors modulating SV movements, we performed real-time imaging analysis of fluorescently labeled SVs in giant calyceal and conventional hippocampal terminals. Compared with small hippocampal terminals, SV movements in giant calyceal terminals were faster, longer and kinetically more heterogeneous. Morphological maturation of giant calyceal terminals was associated with an overall reduction in SV mobility and displacement heterogeneity...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432143/focal-local-field-potential-lfp-signature-of-the-single-axon-monosynaptic-thalamocortical-connection
#3
Espen Hagen, Janne C Fossum, Klas H Pettersen, Jose-Manuel Alonso, Harvey A Swadlow, Gaute T Einevolla
Recent years have seen a resurgence in use of the extracellularly recorded local field potential (LFP) to investigate neural network activity. To probe monosynaptic thalamic activation of cortical postsynaptic target cells, so called spike-trigger-averaged LFP (stLFP) signatures have been measured. In these experiments the cortical LFP is measured by means of multielectrodes covering several cortical lamina and averaged on spontaneous spikes of thalamocortical (TC) cells. Using a well-established forward-modeling scheme, we investigate the biophysical origin of this stLFP signature with simultaneous synaptic activation of cortical layer 4 neurons, mimicking the effect of a single afferent spike from a single TC neuron...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432141/the-spacing-effect-for-structural-synaptic-plasticity-provides-specificity-and-precision-in-plastic-changes
#4
Martin A San, L Rela, B D Gelb, M R Pagani
In contrast to trials of training without intervals (massed training), training trials spaced over time (spaced training) induce a more persistent memory identified as long-term memory (LTM). This phenomenon known as "the spacing effect for memory" is poorly understood. LTM is supported by structural synaptic plasticity; however, how synapses integrate spaced stimuli remains elusive. Here, we analyzed events of structural synaptic plasticity at the single synapse level after distinct patterns of stimulation in motoneurons of Drosophila We found that the spacing effect is a phenomenon detected at synaptic level, which determine the specificity and the precision in structural synaptic plasticity...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28432138/inhibition-of-drp1-ameliorates-synaptic-depression-a%C3%AE-deposition-and-cognitive-impairment-in-alzheimer-s-disease-model
#5
Seung-Hyun Baek, So Jung Park, Jae In Jeong, Sung Hyun Kim, Jihoon Han, Jae Won Kyung, Sang-Ha Baik, Yuri Choi, Bo-Youn Choi, Jinsu Park, Gahee Bahn, Ji Hyun Shin, Doo Sin Jo, Joo-Yong Lee, Choon-Gon Jang, Thiruma V Arumugam, Jongpil Kim, Jeung-Whan Han, Jae-Young Koh, Dong-Hyung Cho, Dong-Gyu Jo
Excessive mitochondrial fission is a prominent early event, and contributes to mitochondrial dysfunction, synaptic failure and neuronal cell death in the progression of Alzheimer's disease (AD). However, it remains to be determined whether inhibition of excessive mitochondrial fission is beneficial in mammal models of AD. To determine whether dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fragmentation, can be a disease-modifying therapeutic target for AD, we examine the effects of Drp1 inhibitor on mitochondrial and synaptic dysfunctions induced by oligomeric β-amyloid (Aβ) in neurons, and neuropathology and cognitive functions in APP/PS1 double transgenic AD mice...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28431972/mitochondrial-energy-metabolism-of-rat-hippocampus-after-treatment-with-the-antidepressants-desipramine-and-fluoxetine
#6
Roberto Federico Villa, Federica Ferrari, Laura Bagini, Antonella Gorini, Nicoletta Brunello, Fabio Tascedda
Alterations in mitochondrial functions have been hypothesized to participate in the pathogenesis of depression, because brain bioenergetic abnormalities have been detected in depressed patients by neuroimaging in vivo studies. However, this hypothesis is not clearly demonstrated in experimental studies: some suggest that antidepressants are inhibitors of mitochondrial metabolism, while others observe the opposite. In this study, the effects of 21-day treatment with desipramine (15 mg/kg) and fluoxetine (10 mg/kg) were examined on the energy metabolism of rat hippocampus, evaluating the catalytic activity of regulatory enzymes of mitochondrial energy-yielding metabolic pathways...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28431369/the-temporal-paradox-of-hebbian-learning-and-homeostatic-plasticity
#7
REVIEW
Friedemann Zenke, Wulfram Gerstner, Surya Ganguli
Hebbian plasticity, a synaptic mechanism which detects and amplifies co-activity between neurons, is considered a key ingredient underlying learning and memory in the brain. However, Hebbian plasticity alone is unstable, leading to runaway neuronal activity, and therefore requires stabilization by additional compensatory processes. Traditionally, a diversity of homeostatic plasticity phenomena found in neural circuits is thought to play this role. However, recent modelling work suggests that the slow evolution of homeostatic plasticity, as observed in experiments, is insufficient to prevent instabilities originating from Hebbian plasticity...
April 18, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28428560/combination-of-high-density-microelectrode-array-and-patch-clamp-recordings-to-enable-studies-of-multisynaptic-integration
#8
David Jäckel, Douglas J Bakkum, Thomas L Russell, Jan Müller, Milos Radivojevic, Urs Frey, Felix Franke, Andreas Hierlemann
We present a novel, all-electric approach to record and to precisely control the activity of tens of individual presynaptic neurons. The method allows for parallel mapping of the efficacy of multiple synapses and of the resulting dynamics of postsynaptic neurons in a cortical culture. For the measurements, we combine an extracellular high-density microelectrode array, featuring 11'000 electrodes for extracellular recording and stimulation, with intracellular patch-clamp recording. We are able to identify the contributions of individual presynaptic neurons - including inhibitory and excitatory synaptic inputs - to postsynaptic potentials, which enables us to study dendritic integration...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428226/rapid-throughput-analysis-of-gabaa-receptor-subtype-modulators-and-blockers-using-disbac1-3-membrane-potential-red-dye
#9
Atefeh Mousavi Nik, Brandon Pressly, Vikrant Singh, Shane Antrobus, Susan Hulsizer, Michael A Rogawski, Heike Wulff, Isaac N Pessah
Fluorometric Imaging Plate Reader (FLIPR®) membrane potential dye (FMP-Red-Dye) is a proprietary tool for basic discovery and high throughput drug screening for G-protein coupled receptors and ion channels. We optimized and validated this potentiometric probe to assay functional modulators of heterologous expressed GABAA receptor (GABAAR) isoforms (synaptic α1β3γ2, extrasynaptic α4β3δ, and β3 homopentomers). High-resolution mass spectrometry identified FMP-Red-dye as DisSBAC1(3). GABAAR expressing cells equilibrated with FMP-Red-Dye exhibited depolarized equilibrium membrane (Em) potentials compared to GABAAR-null cells...
April 20, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28427563/neuroinflammation-in-alzheimer-s-disease-the-preventive-and-therapeutic-potential-of-polyphenolic-nutraceuticals
#10
Yousef Sawikr, Nagendra Sastry Yarla, Ilaria Peluso, Mohammad Amjad Kamal, Gjumrakch Aliev, Anupam Bishayee
Brain inflammation, characterized by increased microglia and astrocyte activation, increases during aging and is a key feature of neurodegenerative diseases, such as Alzheimer's disease (AD). In AD, neuronal death and synaptic impairment, induced by amyloid-β (Aβ) peptide, are at least in part mediated by microglia and astrocyte activation. Glial activation results in the sustained production of proinflammatory cytokines and reactive oxygen species, giving rise to a chronic inflammatory process. Astrocytes are the most abundant glial cells in the central nervous system and are involved in the neuroinflammation...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28425471/nonspecific-synaptic-plasticity-improves-the-recognition-of-sparse-patterns-degraded-by-local-noise
#11
Karen Safaryan, Reinoud Maex, Neil Davey, Rod Adams, Volker Steuber
Many forms of synaptic plasticity require the local production of volatile or rapidly diffusing substances such as nitric oxide. The nonspecific plasticity these neuromodulators may induce at neighboring non-active synapses is thought to be detrimental for the specificity of memory storage. We show here that memory retrieval may benefit from this non-specific plasticity when the applied sparse binary input patterns are degraded by local noise. Simulations of a biophysically realistic model of a cerebellar Purkinje cell in a pattern recognition task show that, in the absence of noise, leakage of plasticity to adjacent synapses degrades the recognition of sparse static patterns...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28425198/the-cell-adhesion-molecule-epha4-is-involved-in-circadian-clock-functions
#12
Silke Kiessling, Emma K O'Callaghan, Marlène Freyburger, Nicolas Cermakian, Valérie Mongrain
Circadian (~24 h) rhythms of cellular network plasticity in the central circadian clock, the suprachiasmatic nucleus (SCN), have been described. The neuronal network in the SCN regulates photic resetting of the circadian clock as well as stability of the circadian system during both entrained and constant conditions. EphA4, a cell adhesion molecule regulating synaptic plasticity by controlling connections of neurons and astrocytes, is expressed in the SCN. To address whether EphA4 plays a role in circadian photoreception and influences the neuronal network of the SCN, we have analysed circadian wheel-running behavior of EphA4 knockout (EphA4(-/-) ) mice under different light conditions and upon photic resetting, as well as their light-induced protein response in the SCN...
April 20, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28424589/the-calcium-channel-c-terminal-and-synaptic-vesicle-tethering-analysis-by-immuno-nanogold-localization
#13
Robert H C Chen, Qi Li, Christine A Snidal, Sabiha R Gardezi, Elise F Stanley
At chemical synapses the incoming action potential triggers the influx of Ca(2+) through voltage-sensitive calcium channels (CaVs, typically CaV2.1 and 2.2) and the ions binds to sensors associated with docked, transmitter filled synaptic vesicles (SVs), triggering their fusion and discharge. The CaVs and docked SVs are located within the active zone (AZ) region of the synapse which faces a corresponding neurotransmitter receptor-rich region on the post-synaptic cell. Evidence that the fusion of a SV can be gated by Ca(2+) influx through a single CaV suggests that the channel and docked vesicle are linked by one or more molecular tethers (Stanley, 1993)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28424512/human-umbilical-cord-plasma-proteins-revitalize-hippocampal-function-in-aged-mice
#14
Joseph M Castellano, Kira I Mosher, Rachelle J Abbey, Alisha A McBride, Michelle L James, Daniela Berdnik, Jadon C Shen, Bende Zou, Xinmin S Xie, Martha Tingle, Izumi V Hinkson, Martin S Angst, Tony Wyss-Coray
Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation and downregulated in the aged brain...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28424292/loss-and-recovery-of-functional-connectivity-in-cultured-cortical-networks-exposed-to-hypoxia
#15
Joost le Feber, Niels Erkamp, Michel J A M van Putten, Jeannette Hofmeijer
In the core of a brain infarct, loss of neuronal function is followed by neuronal death within minutes. In an area surrounding the core (penumbra), some perfusion remains. Here, neurons initially remain structurally intact, but massive synaptic failure strongly reduces neural activity. Activity in the penumbra may eventually recover or further deteriorate towards massive cell death. Besides activity recovery, return of brain functioning requires restoration of connectivity. However, low activity has been shown to initiate compensatory mechanisms that affect network connectivity...
April 19, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28423323/liberated-pka-catalytic-subunits-associate-with-the-membrane-via-myristoylation-to-preferentially-phosphorylate-membrane-substrates
#16
Shane E Tillo, Wei-Hong Xiong, Maho Takahashi, Sheng Miao, Adriana L Andrade, Dale A Fortin, Guang Yang, Maozhen Qin, Barbara F Smoody, Philip J S Stork, Haining Zhong
Protein kinase A (PKA) has diverse functions in neurons. At rest, the subcellular localization of PKA is controlled by A-kinase anchoring proteins (AKAPs). However, the dynamics of PKA upon activation remain poorly understood. Here, we report that elevation of cyclic AMP (cAMP) in neuronal dendrites causes a significant percentage of the PKA catalytic subunit (PKA-C) molecules to be released from the regulatory subunit (PKA-R). Liberated PKA-C becomes associated with the membrane via N-terminal myristoylation...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28423316/diversity-in-excitation-inhibition-mismatch-underlies-local-functional-heterogeneity-in-the-rat-auditory-cortex
#17
Can Tao, Guangwei Zhang, Chang Zhou, Lijuan Wang, Sumei Yan, Huizhong Whit Tao, Li I Zhang, Yi Zhou, Ying Xiong
Cortical neurons are heterogeneous in their functional properties. This heterogeneity is fundamental for the processing of different features of sensory information. However, functional diversity within a local group of neurons is poorly understood. Here, we demonstrate that neighboring cortical neurons in layer 5 but not those of layer 4 of the rat anterior auditory field (AAF) exhibited a surprisingly high level of diversity in tonal receptive fields. In vivo whole-cell voltage-clamp recordings revealed that the diversity of frequency representation was due to a spectral mismatch between synaptic excitation and inhibition to varying degrees...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28422371/effects-of-m1-and-m4-activation-on-excitatory-synaptic-transmission-in-ca1
#18
Catherine Thorn, Michael Popiolek, Eda Stark, Jeremy Edgerton
Hippocampal networks are particularly susceptible to dysfunction in many neurodegenerative diseases and neuropsychiatric disorders including Alzheimer's disease, Lewy body dementia, and schizophrenia. CA1, a major output region of the hippocampus, receives glutamatergic input from both hippocampal CA3 and entorhinal cortex, via the Schaffer collateral (SC) and temporoammonic (TA) pathways, respectively. SC and TA inputs to CA1 are thought to be differentially involved in the retrieval of previously stored memories versus the encoding of novel information, and switching between these two crucial hippocampal functions is thought to critically depend on acetylcholine (ACh) acting at muscarinic receptors...
April 19, 2017: Hippocampus
https://www.readbyqxmd.com/read/28421537/satb2-ablation-impairs-hippocampus-based-long-term-spatial-memory-and-short-term-working-memory-and-immediate-early-genes-iegs-mediated-hippocampal-synaptic-plasticity
#19
Ying Li, Qiang-Long You, Sheng-Rong Zhang, Wei-Yuan Huang, Wen-Jun Zou, Wei Jie, Shu-Ji Li, Ji-Hong Liu, Chuang-Ye Lv, Jin Cong, Yu-Ying Hu, Tian-Ming Gao, Jian-Ming Li
Special AT-rich sequence-binding protein 2 (Satb2) is a protein binding to the matrix attachment regions of DNA and important for gene regulation. Patients with SATB2 mutation usually suffer moderate to severe mental retardation. However, the mechanisms for the defects of intellectual activities in patients with SATB2 mutation are largely unclear. Here we established the heterozygous Satb2 mutant mice and Satb2 conditional knockout mice to mimic the patients with SATB2 mutation and figured out the role of Satb2 in mental activities...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28420966/fast-and-slow-inhibition-in-the-visual-thalamus-is-influenced-by-allocating-gabaa-receptors-with-different-%C3%AE-subunits
#20
Stephen G Brickley, Zhiwen Ye, Xiao Yu, Catriona M Houston, Zahra Aboukhalil, Nicholas P Franks, William Wisden
Cell-type specific differences in the kinetics of inhibitory postsynaptic conductance changes (IPSCs) are believed to impact upon network dynamics throughout the brain. Much attention has focused on how GABAA receptor (GABAAR) α and β subunit diversity will influence IPSC kinetics, but less is known about the influence of the γ subunit. We have examined whether GABAAR γ subunit heterogeneity influences IPSC properties in the thalamus. The γ2 subunit gene was deleted from GABAARs selectively in the dorsal lateral geniculate nucleus (dLGN)...
2017: Frontiers in Cellular Neuroscience
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