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https://www.readbyqxmd.com/read/29228003/a-mig-15-jnk-1-map-kinase-cascade-opposes-rpm-1-signaling-in-synapse-formation-and-learning
#1
Oliver Crawley, Andrew C Giles, Muriel Desbois, Sudhanva Kashyap, Rayna Birnbaum, Brock Grill
The Pam/Highwire/RPM-1 (PHR) proteins are conserved intracellular signaling hubs that regulate synapse formation and axon termination. The C. elegans PHR protein, called RPM-1, acts as a ubiquitin ligase to inhibit the DLK-1 and MLK-1 MAP kinase pathways. We have identified several kinases that are likely to form a new MAP kinase pathway that suppresses synapse formation defects, but not axon termination defects, in the mechanosensory neurons of rpm-1 mutants. This pathway includes: MIG-15 (MAP4K), NSY-1 (MAP3K), JKK-1 (MAP2K) and JNK-1 (MAPK)...
December 11, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29226549/fasting-induces-astroglial-plasticity-in-the-olfactory-bulb-glomeruli-of-rats
#2
Virginie Daumas-Meyer, Gaëlle Champeil-Potokar, Catherine Chaumontet, Patrice Dahirel, Catherine Papillon, Patrice Congar, Isabelle Denis
The detection of food odors by the olfactory system, which plays a key role in regulating food intake and elaborating the hedonic value of food, is reciprocally influenced by the metabolic state. Fasting increases olfactory performance, notably by increasing the activity of olfactory bulb (OB) neurons. The glutamatergic synapses between olfactory sensory neurons and mitral cells in the OB glomeruli are regulated by astrocytes, periglomerular neurons, and centrifugal afferents. We compared the expansion of astroglial processes by quantifying GFAP-labeled areas in fed and fasted rats to see whether OB glomerular astrocytes are involved in the metabolic sensing and adaptation of the olfactory system...
December 11, 2017: Glia
https://www.readbyqxmd.com/read/29225336/psychiatric-polygenic-risk-associates-with-cortical-morphology-and-functional-organization-in-aging
#3
Annie Lee, Mojun Shen, Anqi Qiu
Common brain abnormalities in cortical morphology and functional organization are observed in psychiatric disorders and aging, reflecting shared genetic influences. This preliminary study aimed to examine the contribution of a polygenetic risk for psychiatric disorders (PRScross) to aging brain and to identify molecular mechanisms through the use of multimodal brain images, genotypes, and transcriptome data. We showed age-related cortical thinning in bilateral inferior frontal cortex (IFC) and superior temporal gyrus and alterations in the functional connectivity between bilateral IFC and between right IFC and right inferior parietal lobe as a function of PRScross...
December 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29225045/post-reexposure-administration-of-riluzole-attenuates-the-reconsolidation-of-conditioned-fear-memory-in-rats
#4
Kie Akagi, Misa Yamada, Akiyoshi Saitoh, Jun-Ichiro Oka, Mitsuhiko Yamada
Recently, we demonstrated that riluzole, which has been shown to block the glutamatergic system, facilitates fear extinction in rats. Here, we undertook experiments on contextual fear conditioning to clarify the actions of riluzole on the reconsolidation of fear memory in rats. We used the fast-acting benzodiazepine midazolam as a reconsolidation-inhibiting control drug. We demonstrated that riluzole (3 mg/kg) and midazolam (1 mg/kg) impaired the reconsolidation of contextual fear memory. Results from spontaneous recovery experiments also suggested that riluzole attenuated reconsolidation...
December 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29225042/endogenous-dopamine-and-endocannabinoid-signaling-mediate-cocaine-induced-reversal-of-ampar-synaptic-potentiation-in-the-nucleus-accumbens-shell
#5
Anna E Ingebretson, Matthew C Hearing, Ethan D Huffington, Mark J Thomas
Repeated exposure to drugs of abuse alters the structure and function of neural circuits mediating reward, generating maladaptive plasticity in circuits critical for motivated behavior. Within meso-corticolimbic dopamine circuitry, repeated exposure to cocaine induces progressive alterations in AMPAR-mediated glutamatergic synaptic transmission. During a 10-14 day period of abstinence from cocaine, AMPAR signaling is potentiated at synapses on nucleus accumbens (NAc) medium spiny neurons (MSNs), promoting a state of heightened synaptic excitability...
December 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29224956/bidirectional-shift-of-group-iii-metabotropic-glutamate-receptor-mediated-synaptic-depression-in-the-epileptic-hippocampus
#6
Fabian Dammann, Timo Kirschstein, Xiati Guli, Steffen Müller, Katrin Porath, Marco Rohde, Tursonjan Tokay, Rüdiger Köhling
A common function of group III metabotropic glutamate receptors (mGluRs) located at the presynaptic site of a glutamatergic synapse is synaptic depression. Here, we studied synaptic depression mediated by group III mGluR activation at Schaffer collateral-CA1 (SC-CA1) synapses and associational-commissural-CA3 (AC-CA3) synapses by recording field excitatory postsynaptic potentials in the in vitro brain slice preparation. In order to gauge the impact of synaptic depression in chronically epileptic tissue, we compared rats after pilocarpine-induced status epilepticus (post-SE) with control animals...
December 7, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/29224722/nrap-1-is-a-presynaptically-released-nmda-receptor-auxiliary-protein-that-modifies-synaptic-strength
#7
Ning Lei, Jerry E Mellem, Penelope J Brockie, David M Madsen, Andres V Maricq
NMDA receptors (NMDARs) are a subtype of postsynaptic ionotropic glutamate receptors that function as molecular coincidence detectors, have critical roles in models of learning, and are associated with a variety of neurological and psychiatric disorders. To date, no auxiliary proteins that modify NMDARs have been identified. Here, we report the identification of NRAP-1, an auxiliary protein in C. elegans that modulates NMDAR function. NMDAR-mediated currents were eliminated in nrap-1 mutants, as was NMDA-dependent behavior...
December 1, 2017: Neuron
https://www.readbyqxmd.com/read/29224573/brain-glutamate-in-medication-free-depressed-patients-a-proton-mrs-study-at-7-tesla
#8
Beata R Godlewska, Charles Masaki, Ann L Sharpley, Philip J Cowen, Uzay E Emir
BACKGROUND: The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5-3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx...
December 11, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/29223874/the-hypoxia-tolerant-vertebrate-brain-arresting-synaptic-activity
#9
Leslie T Buck, Matthew E Pamenter
The ion channel arrest hypothesis has been the foundation of three decades of research into the underlying mechanisms of hypoxia/anoxia tolerance in several key species, including: painted turtles, goldfish, crucian carp, naked mole rats, and arctic and ground squirrels. The hypothesis originally stated that hypoxia/anoxia tolerant species ought to have fewer ion channels per area membrane and/or mechanisms to regulate the permeability of ions through channels. Today we can add to this and include mechanisms to remove channels from membranes and the expression of low conductance isoforms...
December 6, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29223596/presence-and-persistence-of-the-amnesic-shellfish-poisoning-toxin-domoic-acid-in-octopus-and-cuttlefish-brains
#10
Vanessa M Lopes, Rui Rosa, Pedro R Costa
Domoic acid (DA) is a neurotoxin that causes degenerative damage to brain cells and induces permanent short-term memory loss in mammals. In cephalopod mollusks, although DA is known to accumulate primarily in the digestive gland, there is no knowledge whether DA reaches their central nervous system. Here we report, for the first time, the presence of DA in brain tissue of the common octopus (Octopus vulgaris) and the European cuttlefish (Sepia officinalis), and its absence in the brains of several squid species (Loligo vulgaris, L...
December 5, 2017: Marine Environmental Research
https://www.readbyqxmd.com/read/29222692/advances-in-understanding-hilar-mossy-cells-of-the-dentate-gyrus
#11
REVIEW
Helen E Scharfman
Hilar mossy cells (MCs) of the dentate gyrus (DG) distinguish the DG from other hippocampal subfields (CA1-3) because there are two glutamatergic cell types in the DG rather than one. Thus, in the DG, the main cell types include glutamatergic granule cells (GCs) and MCs, whereas in CA1-3, the only glutamatergic cell type is the pyramidal cell. In contrast to GCs, MCs are different in morphology, intrinsic electrophysiological properties, afferent input and axonal projections, so their function is likely to be very different from GCs...
December 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29222130/stargazin-and-cornichon-3-relieve-polyamine-block-of-ampa-receptors-by-enhancing-blocker-permeation
#12
Patricia M G E Brown, Hugo McGuire, Derek Bowie
Most ligand- and voltage-gated ion channels assemble as signaling complexes consisting of pore-forming and auxiliary subunits. In the mammalian brain, AMPA-type ionotropic glutamate receptors (AMPARs) coassemble with several families of auxiliary subunits that regulate channel gating as well as ion channel block and permeation. Previous work has shown that auxiliary proteins stargazin (or γ2) and cornichon-3 (CNIH-3) attenuate the cytoplasmic polyamine channel block of AMPARs, although the underlying mechanism has yet to be established...
December 8, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29221791/online-effects-of-transcranial-direct-current-stimulation-on-prefrontal-metabolites-in-gambling-disorder
#13
Maya Dickler, Christophe Lenglos, Emmanuelle Renauld, Francine Ferland, Richard A Edden, Jean Leblond, Shirley Fecteau
Gambling disorder is characterized by persistent maladaptive gambling behaviors and is now considered among substance-related and addictive disorders. There is still unmet therapeutic need for these clinical populations, however recent advances indicate that interventions targeting the Glutamatergic/GABAergic system hold promise in reducing symptoms in substance-related and addictive disorders, including gambling disorder. There is some data indicating that transcranial direct current stimulation may hold clinical benefits in substance use disorders and modulate levels of brain metabolites including glutamate and GABA...
December 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29221161/piriform-cortical-glutamatergic-and-gabaergic-neurons-express-coordinated-plasticity-for-whisker-induced-odor-recall
#14
Yahui Liu, Zilong Gao, Changfeng Chen, Bo Wen, Li Huang, Rongjing Ge, Shidi Zhao, Ruichen Fan, Jing Feng, Wei Lu, Liping Wang, Jin-Hui Wang
Neural plasticity occurs in learning and memory. Coordinated plasticity at glutamatergic and GABAergic neurons during memory formation remains elusive, which we investigate in a mouse model of associative learning by cellular imaging and electrophysiology. Paired odor and whisker stimulations lead to whisker-induced olfaction response. In mice that express this cross-modal memory, the neurons in the piriform cortex are recruited to encode newly acquired whisker signal alongside innate odor signal, and their response patterns to these associated signals are different...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220673/de-novo-variants-in-gria4-lead-to-intellectual-disability-with-or-without-seizures-and-gait-abnormalities
#15
Sonja Martin, Adam Chamberlin, Deepali N Shinde, Maja Hempel, Tim M Strom, Allison Schreiber, Jessika Johannsen, Lilian Bomme Ousager, Martin J Larsen, Lars Kjaersgaard Hansen, Ali Fatemi, Julie S Cohen, Johannes Lemke, Kristina P Sørensen, Katherine L Helbig, Davor Lessel, Rami Abou Jamra
Using trio whole-exome sequencing, we have identified de novo heterozygous pathogenic variants in GRIA4 in five unrelated individuals with intellectual disability and other symptoms. GRIA4 encodes an AMPA receptor subunit known as GluR4, which is found on excitatory glutamatergic synapses and is important for learning and memory. Four of the variants are located in the highly conserved SYTANLAAF motif in the transmembrane protein M3, and the fifth is in an extra-cellular domain. Molecular modeling of the altered protein showed that three of the variants in the SYTANLAAF motif orient toward the center of the pore region and most likely lead to disturbance of the gating mechanism...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29219634/using-molecular-imaging-to-understand-early-schizophrenia-related-psychosis-neurochemistry-a-review-of-human-studies
#16
Christin Schifani, Sina Hafizi, Tania Da Silva, Jeremy Joseph Watts, M Saad Khan, Romina Mizrahi
Schizophrenia is a chronic psychiatric disorder generally preceded by a so-called prodromal phase, which is characterized by attenuated psychotic symptoms. Advances in clinical research have enabled prospective identification of those individuals who are at clinical high risk (CHR) for psychosis, with the power to predict psychosis onset within the near future. Changes in several brain neurochemical systems and molecular mechanisms are implicated in the pathophysiology of schizophrenia and the psychosis spectrum, including the dopaminergic, γ-aminobutyric acid (GABA)-ergic, glutamatergic, endocannabinoid, and immunologic (i...
December 8, 2017: International Review of Psychiatry
https://www.readbyqxmd.com/read/29218821/activity-dependent-control-of-nmda-receptor-subunit-composition-at-hippocampal-mossy-fibre-synapses
#17
Mario Carta, Bettadapura N Srikumar, Adam Gorlewicz, Nelson Rebola, Christophe Mulle
Single neurons express NMDARs with distinct subunit composition and biophysical properties which can be segregated in an input-specific manner. The dynamic control of the heterogeneous distribution of synaptic NMDARs is crucial to control input-dependent synaptic integration and plasticity. In hippocampal CA3 pyramidal cells (CA3 PCs) from mice of both sexes, we found that mossy fibre (Mf) synapses display a markedly lower proportion of GluN2B containing NMDARs than associative/commissural synapses. The mechanism involved in such heterogeneous distribution of GluN2B subunits is not known...
December 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29217157/functional-histamine-h3-and-adenosine-a2a-receptor-heteromers-in-recombinant-cells-and-rat-striatum
#18
Ricardo Márquez-Gómez, Meridith T Robins, Citlaly Gutiérrez-Rodelo, Juan-Manuel Arias, Jesús-Alberto Olivares-Reyes, Richard M van Rijn, José-Antonio Arias-Montaño
In the striatum, histamine H3 receptors (H3Rs) are co-expressed with adenosine A2A receptors (A2ARs) in the cortico-striatal glutamatergic afferents and the GABAergic medium-sized spiny neurons that originate from the indirect pathway of the basal ganglia. This location allows H3Rs and A2ARs to regulate the striatal GABAergic and glutamatergic transmission. However, whether these receptors can physically interact has not yet been assessed. To test this hypothesis, a heteromer-selective in vitro assay was used to detect functional complementation between a chimeric A2AR302-Gαqi4 and wild-type H3Rs in transfected HEK-293 cells...
December 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29216450/endocannabinoid-actions-on-cortical-terminals-orchestrate-local-modulation-of-dopamine-release-in-the-nucleus-accumbens
#19
Yolanda Mateo, Kari A Johnson, Dan P Covey, Brady K Atwood, Hui-Ling Wang, Shiliang Zhang, Iness Gildish, Roger Cachope, Luigi Bellocchio, Manuel Guzmán, Marisela Morales, Joseph F Cheer, David M Lovinger
Dopamine (DA) transmission mediates numerous aspects of behavior. Although DA release is strongly linked to firing of DA neurons, recent developments indicate the importance of presynaptic modulation at striatal dopaminergic terminals. The endocannabinoid (eCB) system regulates DA release and is a canonical gatekeeper of goal-directed behavior. Here we report that extracellular DA increases induced by selective optogenetic activation of cholinergic neurons in the nucleus accumbens (NAc) are inhibited by CB1 agonists and eCBs...
December 6, 2017: Neuron
https://www.readbyqxmd.com/read/29215865/identification-of-fluorescent-small-molecule-compounds-for-synaptic-labeling-by-image-based-high-content-screening
#20
Matthew Dunn, Umed Boltaev, Anne Beskow, Sergey Pampou, Ronald Realubit, Torcato Meira, João Vaz Silva, Rose Reeb, Charles Karan, Steffen Jockusch, David Sulzer, Young-Tae Chang, Dalibor Sames, Clarissa Waites
Few tools are available for non-invasive imaging of synapses in the living mammalian brain. Current paradigms require the use of genetically modified mice or viral delivery of genetic material to the brain. To develop an alternative chemical approach, utilizing the recognition of synaptic components by organic small molecules, we designed an imaging-based, high-content screen in cultured cortical neurons to identify molecules based on their colocalization with fluorescently-tagged synaptic proteins. We used this approach to screen a library of ~7,000 novel fluorescent dyes, and identified a series of compounds in the xanthone family that exhibited consistent synaptic labeling...
December 7, 2017: ACS Chemical Neuroscience
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