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https://www.readbyqxmd.com/read/27931146/d-cycloserine-restores-experience-dependent-neuroplasticity-after-tbi-in-the-developing-rat-brain
#1
Naomi Sulit Sta Maria, Maxine Lane Reger, Yan Cai, Mary Anne Tezheart Mercado Baquing, Floyd Buen, Aditya Ponnaluri, David Hovda, Neil G Harris, Christopher C Giza
Traumatic brain injury (TBI) in children can cause persisting cognitive and behavioral dysfunction and inevitably raises concerns about lost potential in these injured youths. Lateral fluid percussion injury (FPI) in weanling rats pathologically affects hippocampal NMDAR- and AMPAR-mediated glutamatergic neurotransmission subacutely, within the first post-injury week. FPI to weanling rats has also been shown to impair enriched-environment (EE) induced enhancement of Morris water maze (MWM) learning and memory in adulthood...
December 8, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27930673/dopamine-neurons-change-the-type-of-excitability-in-response-to-stimuli
#2
Ekaterina O Morozova, Denis Zakharov, Boris S Gutkin, Christopher C Lapish, Alexey Kuznetsov
The dynamics of neuronal excitability determine the neuron's response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance-based biophysical model, and its regulation by intrinsic and synaptic currents. Calibrating the model to reproduce low frequency tonic firing results in N-methyl-D-aspartate (NMDA) excitation balanced by γ-Aminobutyric acid (GABA)-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27906494/alcohol-dependent-molecular-adaptations-of-the-nmda-receptor-system
#3
REVIEW
Nadege Morisot, Dorit Ron
Phenotypes such as motivation to consume alcohol, goal-directed alcohol seeking and habit formation contribute to the mechanisms underlying heavy alcohol use. Learning and memory processes greatly contribute to the establishment and maintenance of these behavioral phenotypes. The N-Methyl-D-Aspartate receptor (NMDAR) is a driving force of synaptic plasticity, a key cellular hallmark of learning and memory. Here, we describe data in rodents and humans linking signaling molecules that center around the NMDARs and behaviors associated with the development and/or maintenance of alcohol abuse...
December 1, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27903732/parkin-deficiency-reduces-hippocampal-glutamatergic-neurotransmission-by-impairing-ampa-receptor-endocytosis
#4
Giuseppe P Cortese, Mei Zhu, Damian Williams, Sarah Heath, Clarissa L Waites
: Mutations in the gene encoding Parkin, an E3 ubiquitin ligase, lead to juvenile-onset Parkinson's disease by inducing the selective death of midbrain dopaminergic neurons. Accumulating evidence indicates that Parkin also has an important role in excitatory glutamatergic neurotransmission, although its precise mechanism of action remains unclear. Here, we investigate Parkin's role at glutamatergic synapses of rat hippocampal neurons. We find that Parkin-deficient neurons exhibit significantly reduced AMPA receptor (AMPAR)-mediated currents and cell-surface expression, and that these phenotypes result from decreased postsynaptic expression of the adaptor protein Homer1, which is necessary for coupling AMPAR endocytic zones with the postsynaptic density...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27832601/calcium-dynamics-and-regulation-in-horizontal-cells-of-the-vertebrate-retina-lessons-from-teleosts
#5
Michael William Country, Michael G Jonz
Horizontal cells (HCs) are inhibitory interneurons of the vertebrate retina. Unlike typical neurons, HCs are chronically depolarized in the dark, leading to a constant influx of Ca(2+) Therefore, mechanisms of Ca(2+) homeostasis in HCs must differ from neurons elsewhere in the central nervous system, which undergo excitotoxicity when they are chronically depolarized or stressed with Ca(2+) Horizontal cells are especially well characterized in teleost fish, and have been used to unlock mysteries of the vertebrate retina for over a century...
November 2, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27826230/ampa-receptors-are-involved-in-store-operated-calcium-entry-and-interact-with-stim-proteins-in-rat-primary-cortical-neurons
#6
Joanna Gruszczynska-Biegala, Maria Sladowska, Jacek Kuznicki
The process of store-operated calcium entry (SOCE) leads to refilling the endoplasmic reticulum (ER) with calcium ions (Ca(2+)) after their release into the cytoplasm. Interactions between (ER)-located Ca(2+) sensors (stromal interaction molecule 1 [STIM1] and STIM2) and plasma membrane-located Ca(2+) channel-forming protein (Orai1) underlie SOCE and are well described in non-excitable cells. In neurons, however, SOCE appears to be more complex because of the importance of Ca(2+) influx via voltage-gated or ionotropic receptor-operated Ca(2+) channels...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27823947/coexisting-neuronal-autoantibodies-among-children-with-demyelinating-syndromes
#7
Hikmet Kıztanır, Gonca Bektaş, Edibe Pembegül Yıldız, Tuğçe Aksu Uzunhan, Burak Tatlı, Nur Aydınlı, Mine Çalışkan, Meral Özmen
OBJECTIVES: To determine the incidence and clinical relevance of neuronal autoantibodies in children with demyelinating syndromes. METHODS: We conducted a prospective study including 31 consecutive children with demyelinating syndromes. Four patients with N-Methyl-D-aspartate receptor (NMDAR) encephalitis, 32 patients with Guillain-Barre syndrome, 13 children with benign childhood epilepsy, and 28 healthy children were used as controls. Prior to initiating immunomodulatory therapy, serum samples were tested for antibodies against NMDAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) 1, AMPAR2, leucine-rich glioma-activated protein 1, contactin-associated protein 2, gamma-aminobutyric acid B receptors, paraneoplastic ma antigen 2 (PNMA2/Ta), Yo, Ri, Hu, CV2, amphiphysin, and aquaporin-4 by indirect immunofluorescence assays...
November 4, 2016: Brain & Development
https://www.readbyqxmd.com/read/27820843/involvement-of-glud2-in-fear-conditioned-bradycardia-in-mice
#8
Hiroko Kotajima-Murakami, Sakae Narumi, Michisuke Yuzaki, Dai Yanagihara
Lesions in the cerebellar vermis abolish acquisition of fear-conditioned bradycardia in animals and human patients. The δ2 glutamate receptor (GluD2) is predominantly expressed in cerebellar Purkinje cells. The mouse mutant ho15J carries a spontaneous mutation in GluD2 and these mice show a primary deficiency in parallel fiber-Purkinje cell synapses, multiple innervations of Purkinje cells by climbing fibers, and impairment of long-term depression. In the present study, we used ho15J mice to investigate the role of the cerebellum in fear-conditioned bradycardia...
2016: PloS One
https://www.readbyqxmd.com/read/27810933/nmdars-adapt-to-neurotoxic-hiv-protein-tat-downstream-of-a-glun2a-ubiquitin-ligase-signaling-pathway
#9
Matthew V Green, Stanley A Thayer
: HIV-associated neurocognitive disorder (HAND) affects about half of HIV-infected patients. Infected non-neuronal cells release neurotoxic factors such as the viral protein, transactivator of transcription (Tat), that potentiate NMDAR function. NMDARs regulate synaptic changes observed following exposure to HIV proteins, which may underlie cognitive impairment in HAND patients. Here we used patch-clamp recording to measure NMDAR-mediated currents in rat hippocampal cultures following exposure to Tat...
November 3, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27798131/cocaine-exposure-enhances-the-activity-of-ventral-tegmental-area-dopamine-neurons-via-calcium-impermeable-nmdars
#10
Meaghan Creed, Jennifer Kaufling, Giulia R Fois, Marion Jalabert, Tifei Yuan, Christian Lüscher, Francois Georges, Camilla Bellone
: Potentiation of excitatory inputs onto dopamine neurons of the ventral tegmental area (VTA) induced by cocaine exposure allows remodeling of the mesocorticolimbic circuitry, which ultimately drives drug-adaptive behavior. This potentiation is mediated by changes in NMDAR and AMPAR subunit composition. It remains unknown how this synaptic plasticity affects the activity of dopamine neurons. Here, using rodents, we demonstrate that a single cocaine injection increases the firing rate and bursting activity of VTA dopamine neurons, and that these increases persist for 7 d...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27793771/lithium-increases-synaptic-glua2-in-hippocampal-neurons-by%C3%A2-elevating-the-%C3%AE-catenin-protein
#11
Mobeen Farooq, Seonil Kim, Sunny Patel, Latika Khatri, Takuya Hikima, Margaret E Rice, Edward B Ziff
Lithium (Li(+)) is a drug widely employed for treating bipolar disorder, however the mechanism of action is not known. Here we study the effects of Li(+) in cultured hippocampal neurons on a synaptic complex consisting of δ-catenin, a protein associated with cadherins whose mutation is linked to autism, and GRIP, an AMPA receptor (AMPAR) scaffolding protein, and the AMPAR subunit, GluA2. We show that Li(+) elevates the level of δ-catenin in cultured neurons. δ-catenin binds to the ABP and GRIP proteins, which are synaptic scaffolds for GluA2...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27790093/synaptic-conductances-during-interictal-discharges-in-pyramidal-neurons-of-rat-entorhinal-cortex
#12
Dmitry V Amakhin, Julia L Ergina, Anton V Chizhov, Aleksey V Zaitsev
In epilepsy, the balance of excitation and inhibition underlying the basis of neural network activity shifts, resulting in neuronal network hyperexcitability and recurrent seizure-associated discharges. Mechanisms involved in ictal and interictal events are not fully understood, in particular, because of controversial data regarding the dynamics of excitatory and inhibitory synaptic conductances. In the present study, we estimated AMPAR-, NMDAR-, and GABAA R-mediated conductances during two distinct types of interictal discharge (IID) in pyramidal neurons of rat entorhinal cortex in cortico-hippocampal slices...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27784625/nicotine-induced-neuroplasticity-counteracts-the-effect-of-schizophrenia-linked-neuregulin-1-signaling-on-nmdar-function-in-the-rat-hippocampus
#13
Yoshihiko Yamazaki, Katumi Sumikawa
A high rate of heavy tobacco smoking among people with schizophrenia has been suggested to reflect self-medication and amelioration of cognitive dysfunction, a core feature of schizophrenia. NMDAR hypofunction is hypothesized to be a mechanism of cognitive dysfunction, and excessive schizophrenia-linked neuregulin 1 (NRG1) signaling through its receptor ErbB4 can suppress NMDAR function by preventing Src-mediated enhancement of NMDAR responses. Here we investigated whether chronic nicotine exposure in rats by subcutaneous injection of nicotine (0...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27783277/egar-a-food-protein-derived-tetrapeptide-reduces-seizure-activity-in-pentylenetetrazole-induced-epilepsy-models-through-%C3%AE-amino-3-hydroxy-5-methyl-4-isoxazole-propionate-receptors
#14
Song Cai, Chuwen Ling, Jun Lu, Songwei Duan, Yingzhao Wang, Huining Zhu, Ruibang Lin, Liang Chen, Xingchang Pan, Muyi Cai, Huaiyu Gu
A primary pathogeny of epilepsy is excessive activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs). To find potential molecules to inhibit AMPARs, high-throughput screening was performed in a library of tetrapeptides in silico. Computational results suggest that some tetrapeptides bind stably to the AMPAR. We aligned these sequences of tetrapeptide candidates with those from in vitro digestion of the trout skin protein. Among salmon-derived products, Glu-Gly-Ala-Arg (EGAR) showed a high biological affinity toward AMPAR when tested in silico...
October 25, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27762270/%C3%AE-adrenergic-receptors-regulate-the-acquisition-and-consolidation-phases-of-aversive-memory-formation-through-distinct-temporally-regulated-signaling-pathways
#15
Hillary C Schiff, Joshua P Johansen, Mian Hou, David E A Bush, Emily K Smith, JoAnna E Klein, Joseph E LeDoux, Robert M Sears
Memory formation requires the temporal coordination of molecular events and cellular processes following a learned event. During Pavlovian threat (fear) conditioning (PTC), sensory and neuromodulatory inputs converge on post-synaptic neurons within the lateral nucleus of the amygdala (LA). By activating an intracellular cascade of signaling molecules, these G-protein-coupled neuromodulatory receptors are capable of recruiting a diverse profile of plasticity-related proteins. Here we report that norepinephrine, through its actions on β-adrenergic receptors (βARs), modulates aversive memory formation following PTC through two molecularly and temporally distinct signaling mechanisms...
November 16, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27739540/nmda-receptors-in-mouse-anterior-piriform-cortex-initialize-early-odor-preference-learning-and-l-type-calcium-channels-engage-for-long-term-memory
#16
Bandhan Mukherjee, Qi Yuan
The interactions of L-type calcium channels (LTCCs) and NMDA receptors (NMDARs) in memories are poorly understood. Here we investigated the specific roles of anterior piriform cortex (aPC) LTCCs and NMDARs in early odor preference memory in mice. Using calcium imaging in aPC slices, LTCC activation was shown to be dependent on NMDAR activation. Either D-APV (NMDAR antagonist) or nifedipine (LTCC antagonist) reduced somatic calcium transients in pyramidal cells evoked by lateral olfactory tract stimulation. However, nifedipine did not further reduce calcium in the presence of D-APV...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27721179/acute-ampakine-treatment-ameliorates-age-related-deficits-in-long-term-potentiation
#17
Daniel P Radin, Sheng Zhong, Richard Purcell, Arnold Lippa
Memory loss observed as a consequence of aging is paralleled by a down-regulation of AMPA-type glutamate receptors (AMPARs) that mediate fast excitatory synaptic transmission. Activation of these receptors enhances long-term potentiation (LTP), a neuronal process demonstrated to be crucial for memory storage and thought to be a cellular substrate of learning and memory. In the present studies, we determined that LTP was reduced in aged rats when compared to young rats and that acute treatment with CX1846, a novel AMPAR positive allosteric modulator, fifteen minutes prior to tetanic stimulation completely reversed the significant deficit in LTP observed in aged rats...
October 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27708157/amyloid-%C3%AE-effects-on-synapses-and-memory-require-ampa-receptor-subunit-glua3
#18
Niels R Reinders, Yvonne Pao, Maria C Renner, Carla M da Silva-Matos, Tessa R Lodder, Roberto Malinow, Helmut W Kessels
Amyloid-β (Aβ) is a prime suspect for causing cognitive deficits during the early phases of Alzheimer's disease (AD). Experiments in AD mouse models have shown that soluble oligomeric clusters of Aβ degrade synapses and impair memory formation. We show that all Aβ-driven effects measured in these mice depend on AMPA receptor (AMPAR) subunit GluA3. Hippocampal neurons that lack GluA3 were resistant against Aβ-mediated synaptic depression and spine loss. In addition, Aβ oligomers blocked long-term synaptic potentiation only in neurons that expressed GluA3...
October 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27707810/gsg1l-regulates-the-strength-of-ampa-receptor-mediated-synaptic-transmission-but-not-ampa-receptor-kinetics-in-hippocampal-dentate-granule-neurons
#19
Xia Mao, Xinglong Gu, Wei Lu
GSG1L is an AMPA receptor (AMPAR) auxiliary subunit that regulates AMPAR trafficking and function in hippocampal CA1 pyramidal neurons. However, its physiological roles in other types of neurons remain to be characterized. Here we investigated the role of GSG1L in hippocampal dentate granule cells, and found that GSG1L is important for the regulation of synaptic strength, but is not critical for the modulation of AMPAR deactivation and desensitization kinetics. These data demonstrate a neuronal type-specific role of GSG1L and suggest that physiological function of AMPAR auxiliary subunits may vary in different types of neurons...
October 5, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27707506/fast-interaction-between-ampa-and-nmda-receptors-by-intracellular-calcium
#20
Andrei Rozov, Nail Burnashev
Suppression of NMDA receptor (NMDAR)-mediated currents by intracellular Ca(2+) has been described as a negative feedback loop in NMDAR modulation. In the time scale of tenths of milliseconds the depth of the suppression does not depend on the Ca(2+) source. It may be caused by Ca(2+) influx through voltage-gated calcium channels, NMDAR channels or release from intracellular stores. However, NMDARs are often co-expressed in synapses with Ca(2+)-permeable AMPA receptors (AMPARs). Due to significant differences in activation kinetics between these two types of glutamate receptors (GluRs), Ca(2+) entry through AMPARs precedes full activation of NMDARs, and therefore, might have an impact on the amplitude of NMDAR-mediated currents...
September 28, 2016: Cell Calcium
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