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https://www.readbyqxmd.com/read/29150590/subtype-specific-effects-of-dopaminergic-d2-receptor-activation-on-synaptic-trains-in-layer-v-pyramidal-neurons-in-the-mouse-prefrontal-cortex
#1
Jonna M Leyrer-Jackson, Mark P Thomas
In humans, prefrontal cortical areas are known to support executive functions. In mice, these functions are mediated by homologous regions in the medial prefrontal cortex (mPFC). Executive processes are critically dependent on optimal levels of dopamine (DA), but the cellular mechanisms of DA modulation are incompletely understood. Stable patterns of neuronal activity may be sensitive to frequency-dependent changes in synaptic transmission. We characterized the effects of D2 receptor (D2R) activation on short-term excitatory postsynaptic potential (EPSP) dynamics evoked at varying frequencies in the two subtypes of layer V pyramidal neurons in mouse mPFC We isolated NMDA receptor and non-NMDA receptor-mediated components of EPSP trains evoked by stimulating fibers within layer V or layer I...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29150433/tyrosine-phosphorylation-of-munc18-1-inhibits-synaptic-transmission-by-preventing-snare%C3%A2-assembly
#2
Marieke Meijer, Bernhard Dörr, Hanna Ca Lammertse, Chrysanthi Blithikioti, Jan Rt van Weering, Ruud Fg Toonen, Thomas H Söllner, Matthijs Verhage
Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18-1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho-proteomics abolished the stimulatory effect of Munc18-1 on SNARE complex formation ("SNARE-templating") and membrane fusion in vitro Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18-1-null neurons expressing Munc18-1Y473D Synaptic transmission was temporarily restored by high-frequency stimulation, as well as by a Munc18-1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29150182/mature-hippocampal-neurons-require-lis1-for-synaptic-integrity-implications-for-cognition
#3
Anamaria Sudarov, Xin-Jun Zhang, Leighton Braunstein, Eve LoCastro, Shawn Singh, Yu Taniguchi, Ashish Raj, Song-Hai Shi, Holly Moore, M Elizabeth Ross
BACKGROUND: Platelet-activating factor acetylhydrolase 1B1 (LIS1), a critical mediator of neuronal migration in developing brain, is expressed throughout life. However, relatively little is known about LIS1 function in the mature brain. We previously demonstrated that LIS1 involvement in the formation and turnover of synaptic protrusions and synapses of young brain after neuronal migration is complete. Here we examine the requirement for LIS1 to maintain hippocampal circuit function in adulthood...
September 23, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29147852/enhanced-peptide-detection-toward-single-neuron-proteomics-by-reversed-phase-fractionation-capillary-electrophoresis-mass-spectrometry
#4
Sam B Choi, Camille Lombard-Banek, Pablo Muñoz-LLancao, M Chiara Manzini, Peter Nemes
The ability to detect peptides and proteins in single cells is vital for understanding cell heterogeneity in the nervous system. Capillary electrophoresis (CE) nanoelectrospray ionization (nanoESI) provides high-resolution mass spectrometry (HRMS) with trace-level sensitivity, but compressed separation during CE challenges protein identification by tandem HRMS with limited MS/MS duty cycle. Here, we supplemented ultrasensitive CE-nanoESI-HRMS with reversed-phase (RP) fractionation to enhance identifications from protein digest amounts that approximate to a few mammalian neurons...
November 16, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29144441/g-protein-coupled-receptors-targeted-by-analgesic-venom-peptides
#5
REVIEW
James T Daniel, Richard J Clark
Chronic pain is a complex and debilitating condition associated with a large personal and socioeconomic burden. Current pharmacological approaches to treating chronic pain such as opioids, antidepressants and anticonvulsants exhibit limited efficacy in many patients and are associated with dose-limiting side effects that hinder their clinical use. Therefore, improved strategies for the pharmacological treatment of pathological pain are urgently needed. G-protein coupled receptors (GPCRs) are ubiquitously expressed on the surface of cells and act to transduce extracellular signals and regulate physiological processes...
November 16, 2017: Toxins
https://www.readbyqxmd.com/read/29142291/resveratrol-modulates-cocaine-induced-inhibitory-synaptic-plasticity-in-vta-dopamine-neurons-by-inhibiting-phosphodiesterases-pdes
#6
Yan Li, Laikang Yu, Li Zhao, Fanxing Zeng, Qing-Song Liu
Resveratrol is a natural phytoalexin synthesized by plants, including grapes. It displays a wide range of neuroprotective benefits associated with anti-aging. Recent studies have shown that resveratrol regulates dopaminergic transmission and behavioral effects of drugs of abuse. The goal of the present study is to investigate whether and how resveratrol alters basal inhibitory synaptic transmission and cocaine-induced inhibitory synaptic plasticity in dopamine neurons of the ventral tegmental area (VTA). We report that resveratrol elevated cAMP levels by itself and further potentiated a forskolin-induced increase in cAMP levels in midbrain slices, consistent with reported effects of inhibition of phosphodiesterases (PDEs)...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142096/novel-ca-2-dependent-mechanisms-regulate-spontaneous-release-at-excitatory-synapses-onto-ca1-pyramidal-cells
#7
Walter E Babiec, Thomas J O'Dell
Although long thought to simply be a source of synaptic noise, spontaneous, action-potential independent release of neurotransmitter from presynaptic terminals has multiple roles in synaptic function. We explored whether and to what extent the two predominantly proposed mechanisms for explaining spontaneous release, stochastic activation of voltage-gated Ca(2+) channels (VGCCs) or activation of Ca(2+)-sensing receptors (CaSRs) by extracelluar Ca(2+), played a role in the sensitivity of spontaneous release to the level of extracellular Ca(2+) concentration at excitatory synapses at CA1 pyramidal cells of the adult, male mouse hippocampus...
November 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29140112/a-2017-review-of-pharmacotherapy-for-treating-focal-epilepsy-where-are-we-now-and-how-will-treatment-develop
#8
Andreas Schulze-Bonhage
Focal epilepsy is the most common type of epilepsy with approximately 30 million patients affected worldwide. There is a major challenge to develop new antiepileptic treatments as currently approximately one third of patients remain uncontrolled under our best standards of care. Areas covered: An overview is given on first- and second generation antiepileptic drugs and their mechanisms of action, and on recent new strategies for antiepileptic targets, including drugs aiming at disease modification. Expert opinion: Newer antiepileptic drugs have enabled a better tolerated and individualized treatment for many patients...
November 15, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29139159/syntaxin1b-contributes-to-regulation-of-the-dopaminergic-system-through-gaba-transmission-in-the-cns
#9
Tomonori Fujiwara, Takefumi Kofuji, Tatsuya Mishima, Kimio Akagawa
In neuronal plasma membrane, two syntaxin isoforms, HPC-1/syntaxin1A (STX1A) and syntaxin1B (STX1B), are predominantly expressed as soluble N-ethylmaleimide-sensitive fusion attachment protein receptors, also known as t-SNAREs. We previously reported that glutamatergic and GABAergic synaptic transmission is impaired in Stx1b null mutant (Stx1b(-/-) ) mice, but is almost normal in Stx1a null mutant (Stx1a(-/-) ) mice. These observations suggested that STX1A and STX1B have distinct functions in fast synaptic transmission in the central nervous system (CNS)...
November 15, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29138490/bidirectional-modulation-of-hippocampal-synaptic-plasticity-by-dopaminergic-d4-receptors-in-the-ca1-area-of-hippocampus
#10
Sheeja Navakkode, Katherine C M Chew, Sabrina Jia Ning Tay, Qingshu Lin, Thomas Behnisch, Tuck Wah Soong
Long-term potentiation (LTP) is the persistent increase in the strength of the synapses. However, the neural networks would become saturated if there is only synaptic strenghthening. Synaptic weakening could be facilitated by active processes like long-term depression (LTD). Molecular mechanisms that facilitate the weakening of synapses and thereby stabilize the synapses are also important in learning and memory. Here we show that blockade of dopaminergic D4 receptors (D4R) promoted the formation of late-LTP and transformed early-LTP into late-LTP...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138001/pdz-ligand-binding-induced-conformational-coupling-of-the-pdz-sh3-gk-tandems-in-psd-95-family-maguks
#11
Menglong Zeng, Fei Ye, Jia Xu, Mingjie Zhang
DLG MAGUKs are abundantly expressed in glutamatergic synapses, crucial for synaptic transmission and plasticity by anchoring various postsynaptic components including glutamate receptors, downstream scaffold proteins and signaling enzymes. Different DLG members have shared structures and functions, but also contain unique features. How DLG family proteins function individually and cooperatively are largely unknown. Here, we report that PSD-95 PDZ3 directly couples with SH3-GK tandem in a PDZ ligand binding-dependent manner, and the coupling can promote PSD-95 dimerization and multimerization...
November 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29137960/ampa-receptor-translocation-and-phosphorylation-are-induced-by-transcranial-direct-current-stimulation-in-rats
#12
Justin Stafford, Milene L Brownlow, Anthony Qualley, Ryan Jankord
Over the last decade, the interest in transcranial direct current stimulation (tDCS) has continued to increase, along with consideration of how it affects neuroplasticity mechanisms in the brain. Both human and animal studies have demonstrated numerous benefits and, although its application has increased, the neurophysiological mechanisms underlying tDCS' beneficial effects remain largely unknown. Recent studies have shown that long-term potentiation (LTP) increases following tDCS. In this work, we utilized a rodent model of tDCS to directly assess changes in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, a critical protein for enhancing synaptic transmission...
November 11, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29136012/regional-knockdown-of-ndufs4-implicates-a-thalamocortical-circuit-mediating-anesthetic-sensitivity
#13
Renjini Ramadasan-Nair, Jessica Hui, Pavel I Zimin, Leslie S Itsara, Philip G Morgan, Margaret M Sedensky
Knockout of the mitochondrial complex I protein, NDUFS4, profoundly increases sensitivity of mice to volatile anesthetics. In mice carrying an Ndufs4lox/lox gene, adeno-associated virus expressing Cre recombinase was injected into regions of the brain postulated to affect sensitivity to volatile anesthetics. These injections generated otherwise phenotypically wild type mice with region-specific, postnatal inactivation of Ndufs4, minimizing developmental effects of gene loss. Sensitivities to the volatile anesthetics isoflurane and halothane were measured using loss of righting reflex (LORR) and movement in response to tail clamp (TC) as endpoints...
2017: PloS One
https://www.readbyqxmd.com/read/29135436/defective-synaptic-transmission-causes-disease-signs-in-a-mouse-model-of-juvenile-neuronal-ceroid-lipofuscinosis
#14
Benedikt Grünewald, Maren D Lange, Christian Werner, Aet O'Leary, Andreas Weishaupt, Sandy Popp, David A Pearce, Heinz Wiendl, Andreas Reif, Hans C Pape, Klaus V Toyka, Claudia Sommer, Christian Geis
Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3(Δex7/8)) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination...
November 14, 2017: ELife
https://www.readbyqxmd.com/read/29134962/role-of-glutamatergic-projections-from-the-ventral-ca1-to-infralimbic-cortex-in-context-induced-reinstatement-of-heroin-seeking
#15
Na Wang, Feifei Ge, Cailian Cui, Yijing Li, Xiaowei Sun, Linlin Sun, Xinjuan Wang, Shuli Liu, Haolin Zhang, Yan Liu, Meng Jia, Mingda Yang
The prelimbic cortex (PL) and infralimbic cortex (IL) play a role in context-induced reinstatement of heroin seeking in an animal model of drug relapse. Both the PL and IL receive direct glutamatergic projections from the ventral CA1 (vCA1), which is also involved in context-induced reinstatement of cocaine and heroin seeking. Here we studied the role of vCA1-PL and vCA1-IL projections in context-induced reinstatement of heroin seeking by using electrophysiological, neuropharmacological, chemogenetic and molecular methods...
November 14, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29133056/therapeutic-potential-of-songorine-a-diterpenoid-alkaloid-of-the-genus-aconitum
#16
REVIEW
Haroon Khan, Seyed Mohammad Nabavi, Antoni Sureda, Nikolay Mehterov, Diana Gulei, Ioana Berindan-Neagoe, Hiroaki Taniguchi, Atanas G Atanasov
Alkaloids are well-studied secondary metabolites, with recent preclinical studies evidencing that many of them exhibit anti-cancer, anti-depressant, anti-nociceptive, anti-inflammatory, anti-pyretic, anti-platelet, anti-oxidant, and anti-bacterial properties. Aconitum is a genus rich of diverse alkaloids. More than 450 alkaloids have been identified in a variety of species. Songorine is a C20 diterpenoid alkaloid and 12-keto analog of napelline, isolated from Aconitum soongaricum and was associated with a heterogeneous panel of biological functions...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29130788/complex-action-of-tyramine-tryptamine-and-histamine-on-native-and-recombinant-asics
#17
Oleg I Barygin, Margarita S Komarova, Tatyana B Tikhonova, Anastasiia S Korosteleva, Maxim V Nikolaev, Lev G Magazanik, Denis B Tikhonov
Proton-gated channels of the ASIC family are widely distributed in the mammalian brain, and, according to the recent data, participate in synaptic transmission. However, ASIC-mediated currents are small, and special efforts are required to detect them. This prompts the search for endogenous ASIC ligands, which can activate or potentiate these channels. A recent finding of the potentiating action of histamine on recombinant homomeric ASIC1a has directed attention to amine-containing compounds. In the present study, we have analyzed the action of histamine, tyramine, and tryptamine on native and recombinant ASICs...
November 13, 2017: Channels
https://www.readbyqxmd.com/read/29129792/the-hypoxia-mimetic-protocatechuic-acid-ethyl-ester-inhibits-synaptic-signaling-and-plasticity-in-the-rat-hippocampus
#18
Sinead M Lanigan, John J O'Connor
During hypoxia a number of physiological changes occur within neurons including the stabilisation of hypoxia-inducible factors (HIFs). The activity of these proteins is regulated by O2, Fe(2+), 2-OG and ascorbate-dependant hydroxylases which contain prolyl-4-hydroxylase domains (PHDs). PHD inhibitors have been widely used and have been shown to have a preconditioning and protective effect against a later and more severe hypoxic insult. In this study we have investigated the neuroprotective effects of the PHD inhibitor, protocatechuic acid ethyl ester (ethyl 3,4,dihydroxybenzoate: EDHB) as well as its effects on synaptic transmission and plasticity in the rat hippocampus using electrophysiological techniques...
November 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/29126252/monoamines-in-glioblastoma-complex-biology-with-therapeutic-potential
#19
Seamus Patrick Caragher, Robert Raymond Hall, Riasat Ahsan, Atique U Ahmed
Glioblastoma (GBM) is characterized by extremely poor prognoses, despite the use of gross surgical resection, alkylating chemotherapeutic agents, and radiotherapy. Evidence increasingly highlights the role of the tumor microenvironment in enabling this aggressive phenotype. Despite this interest, the role of neurotransmitters, brain-specific messengers underlying synaptic transmission, remains murky. These signaling molecules influence a complex network of molecular pathways and cellular behaviors in many CNS-resident cells including neural stem cells and progenitor cells, neurons, and glia cells...
November 4, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29125502/congenital-myasthenic-syndromes-or%C3%A2-inherited-disorders-of-neuromuscular-transmission-recent-discoveries-and%C3%A2-open%C3%A2-questions
#20
Sophie Nicole, Yoshiteru Azuma, Stéphanie Bauché, Bruno Eymard, Hanns Lochmüller, Clarke Slater
Congenital myasthenic syndromes (CMS) form a heterogeneous group of rare diseases characterized by fatigable muscle weakness. They are genetically-inherited and caused by defective synaptic transmission at the cholinergic neuromuscular junction (NMJ). The number of genes known to cause CMS when mutated is currently 30, and the relationship between fatigable muscle weakness and defective functions is quite well-understood for many of them. However, some of the most recent discoveries in individuals with CMS challenge our knowledge of the NMJ, where the basis of the pathology has mostly been investigated in animal models...
November 8, 2017: Journal of Neuromuscular Diseases
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