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https://www.readbyqxmd.com/read/28103482/synaptic-plasticity-onto-dopamine-neurons-shapes-fear-learning
#1
Marco Pignatelli, George Kwabena Essien Umanah, Sissi Palma Ribeiro, Rong Chen, Senthilkumar Senthil Karuppagounder, Hau-Jie Yau, Stephen Eacker, Valina Lynn Dawson, Ted Murray Dawson, Antonello Bonci
Fear learning is a fundamental behavioral process that requires dopamine (DA) release. Experience-dependent synaptic plasticity occurs on DA neurons while an organism is engaged in aversive experiences. However, whether synaptic plasticity onto DA neurons is causally involved in aversion learning is unknown. Here, we show that a stress priming procedure enhances fear learning by engaging VTA synaptic plasticity. Moreover, we took advantage of the ability of the ATPase Thorase to regulate the internalization of AMPA receptors (AMPARs) in order to selectively manipulate glutamatergic synaptic plasticity on DA neurons...
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28103481/motor-learning-requires-purkinje-cell-synaptic-potentiation-through-activation-of-ampa-receptor-subunit-glua3
#2
Nicolas Gutierrez-Castellanos, Carla M Da Silva-Matos, Kuikui Zhou, Cathrin B Canto, Maria C Renner, Linda M C Koene, Ozgecan Ozyildirim, Rolf Sprengel, Helmut W Kessels, Chris I De Zeeuw
Accumulating evidence indicates that cerebellar long-term potentiation (LTP) is necessary for procedural learning. However, little is known about its underlying molecular mechanisms. Whereas AMPA receptor (AMPAR) subunit rules for synaptic plasticity have been extensively studied in relation to declarative learning, it is unclear whether these rules apply to cerebellum-dependent motor learning. Here we show that LTP at the parallel-fiber-to-Purkinje-cell synapse and adaptation of the vestibulo-ocular reflex depend not on GluA1- but on GluA3-containing AMPARs...
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28103474/learning-about-synaptic-glua3
#3
Zhengping Jia, Graham L Collingridge
In this issue of Neuron, Gutierrez-Castellanos et al. (2017) reveal a critical role for the AMPA receptor subunit GluA3 in cerebellar synaptic plasticity and motor learning in mice.
January 18, 2017: Neuron
https://www.readbyqxmd.com/read/28103235/real-time-multiplicative-memory-amplification-mediated-by-whole-cell-scaling-of-synaptic-response-in-key-neurons
#4
Iris Reuveni, Sourav Ghosh, Edi Barkai
Intense spiking response of a memory-pattern is believed to play a crucial role both in normal learning and pathology, where it can create biased behavior. We recently proposed a novel model for memory amplification where the simultaneous two-fold increase of all excitatory (AMPAR-mediated) and inhibitory (GABAAR-mediated) synapses in a sub-group of cells that constitutes a memory-pattern selectively amplifies this memory. Here we confirm the cellular basis of this model by validating its major predictions in four sets of experiments, and demonstrate its induction via a whole-cell transduction mechanism...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28101525/untangling-basal-ganglia-network-dynamics-and-function-role-of-dopamine-depletion-and-inhibition-investigated-in-a-spiking-network-model
#5
Mikael Lindahl, Jeanette Hellgren Kotaleski
The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28100749/promoted-interaction-of-c-ebp%C3%AE-with-demethylated-cxcr3-gene-promoter-contributes-to-neuropathic-pain-in-mice
#6
Bao-Chun Jiang, Li-Na He, Xiao-Bo Wu, Hui Shi, Wen-Wen Zhang, Zhi-Jun Zhang, De-Li Cao, Chun-Hua Li, Jun Gu, Yong-Jing Gao
: DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and how it contributes to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of the spinal cord. Meanwhile, the CpG (5'-cytosine-phosphate-guanine-3') island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28096498/differential-changes-in-hippocampal-camkii-and-glua1-activity-after-memory-training-involving-different-levels-of-adaptive-forgetting
#7
Nicolas Fraize, Al Mahdy Hamieh, Mickaël Antoine Joseph, Monique Touret, Régis Parmentier, Paul Antoine Salin, Gaël Malleret
Phosphorylation of CaMKII and AMPA receptor GluA1 subunit has been shown to play a major role in hippocampal-dependent long-term/reference memory (RM) and in the expression of long-term synaptic potentiation (LTP). In contrast, it has been proposed that dephosphorylation of these proteins could be involved in the opposite phenomenon of hippocampal long-term synaptic depression (LTD) and in adaptive forgetting. Adaptive forgetting allows interfering old memories to be forgotten to give new ones the opportunity to be stored in memory, and in particular in short-term/working memory (WM) that was shown to be very sensitive to proactive interference...
February 2017: Learning & Memory
https://www.readbyqxmd.com/read/28096412/transmembrane-protein-108-is-required-for-glutamatergic-transmission-in-dentate-gyrus
#8
Hui-Feng Jiao, Xiang-Dong Sun, Ryan Bates, Lei Xiong, Lei Zhang, Fang Liu, Lei Li, Hong-Sheng Zhang, Shun-Qi Wang, Ming-Tao Xiong, Mihir Patel, Alexis M Stranahan, Wen-Cheng Xiong, Bao-Ming Li, Lin Mei
Neurotransmission in dentate gyrus (DG) is critical for spatial coding, learning memory, and emotion processing. Although DG dysfunction is implicated in psychiatric disorders, including schizophrenia, underlying pathological mechanisms remain unclear. Here we report that transmembrane protein 108 (Tmem108), a novel schizophrenia susceptibility gene, is highly enriched in DG granule neurons and its expression increased at the postnatal period critical for DG development. Tmem108 is specifically expressed in the nervous system and enriched in the postsynaptic density fraction...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28093559/gradation-approx-10-size-states-of-synaptic-strength-by-quantal-addition-of-structural-modules
#9
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
#10
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/28092020/early-life-social-isolation-induced-depressive-like-behavior-in-rats-results-in-microglial-activation-and-neuronal-histone-methylation-that-are-mitigated-by-minocycline
#11
Hong-Tao Wang, Fu-Lian Huang, Zhao-Lan Hu, Wen-Juan Zhang, Xiao-Qing Qiao, Yan-Qing Huang, Ru-Ping Dai, Fang Li, Chang-Qi Li
Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microglia, levels of histone methylation, as well as expression of glutamate receptor subunits in the hippocampus. We found that depressive-like behavior was induced after ESI as determined by sucrose preference and forced swimming tests...
January 16, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28088112/a-current-perspective-on-the-oncopreventive-and-oncolytic-properties-of-selective-serotonin-reuptake-inhibitors
#12
REVIEW
Daniel P Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28079433/pet-imaging-of-cannabinoid-type-2-receptors-with-11-c-a-836339-did-not-evidence-changes-following-neuroinflammation-in-rats
#13
Geraldine Pottier, Vanessa Gómez-Vallejo, Daniel Padro, Raphaël Boisgard, Frédéric Dollé, Jordi Llop, Alexandra Winkeler, Abraham Martín
Cannabinoid type 2 receptors (CB2R) have emerged as promising targets for the diagnosis and therapy of brain pathologies. However, no suitable radiotracers for accurate CB2R mapping have been found to date, limiting the investigation of the CB2 receptor expression using positron emission tomography (PET) imaging. In this work, we report the evaluation of the in vivo expression of CB2R with [(11)C]A-836339 PET after cerebral ischemia and in two rat models of neuroinflammation, first by intrastriatal LPS and then by AMPA injection...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
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
#14
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/28077487/calcium-permeable-ampa-receptors-and-silent%C3%A2-synapses-in-cocaine-conditioned-place-preference
#15
Avani Shukla, Anna Beroun, Myrto Panopoulou, Peter A Neumann, Seth Gn Grant, M Foster Olive, Yan Dong, Oliver M Schlüter
Exposure to cocaine generates silent synapses in the nucleus accumbens (NAc), whose eventual unsilencing/maturation by recruitment of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) after drug withdrawal results in profound remodeling of NAc neuro-circuits. Silent synapse-based NAc remodeling was shown to be critical for several drug-induced behaviors, but its role in acquisition and retention of the association between drug rewarding effects and drug-associated contexts has remained unclear. Here, we find that the postsynaptic proteins PSD-93, PSD-95, and SAP102 differentially regulate excitatory synapse properties in the NAc...
January 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28071892/transient-adenosine-release-is-modulated-by-nmda-and-gabab-receptors
#16
Michael D Nguyen, Ying Wang, Mallikarjunarao Ganesana, B Jill Venton
Adenosine is a neuroprotective agent that modulates neurotransmission and is modulated by other neurotransmitters. Spontaneous, transient adenosine is a recently discovered mode of signaling where adenosine is released and cleared from the extracellular space quickly, in less than three seconds. Spontaneous adenosine release is regulated by adenosine A1 and A2a receptors, but regulation by other neurotransmitter receptors has not been studied. Here, we examined the effect of glutamate and GABA receptors on the concentration and frequency of spontaneous, transient adenosine release by measuring adenosine with fast-scan cyclic voltammetry in the rat caudate-putamen...
January 10, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28069928/functional-organization-of-cutaneous-and-muscle-afferent-synapses-onto-immature-spinal-lamina-i-projection-neurons
#17
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/28063882/mice-lacking-grip1-2-show-increased-social-interactions-and-enhanced-phosphorylation-at-glua2-s880
#18
Mei Han, Rebeca Mejias, Shu-Ling Chiu, Rebecca Rose, Abby Adamczyk, Richard Huganir, Tao Wang
Glutamate receptor interacting proteins 1 and 2 (GRIP1/2) play an important role in regulating synaptic trafficking of AMPA receptor 2/3 (GluA2/3) and synaptic strength. Gain-of-function GRIP1 mutations are implicated in social behavioral deficits in autism. To study mechanisms of Grip1/2-mediated AMPA signaling in the regulation of social behaviors, we performed social behavioral testing on neuron-specific Grip1/2-double knockout (DKO) and wild type (WT) mice that are matched for age, sex, and strain background...
January 4, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28059046/long-term-effects-of-aripiprazole-exposure-on-monoaminergic-and-glutamatergic-receptor-subtypes-comparison-with-cariprazine
#19
Yong Kee Choi, Nika Adham, Béla Kiss, István Gyertyán, Frank I Tarazi
OBJECTIVE: This study examined the chronic effects of aripiprazole and cariprazine on serotonin (5-HT1A and 5-HT2A) and glutamate (NMDA and AMPA) receptor subtypes. In addition, the effects of aripiprazole on D2 and D3 receptors were tested and compared with previously reported cariprazine data. METHODS: Rats received vehicle, aripiprazole (2, 5, or 15 mg/kg), or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Receptor levels were quantified using autoradiographic assays on brain sections from the medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), nucleus accumbens (NAc), caudate-putamen medial (CPu-M), caudate-putamen lateral (CPu-L), hippocampal CA1 (HIPP-CA1) and CA3 (HIPP-CA3) regions, and the entorhinal cortex (EC)...
January 6, 2017: CNS Spectrums
https://www.readbyqxmd.com/read/28058675/neuropeptide-cycloprolylglycine-is-an-endogenous-positive-modulator-of-ampa-receptors
#20
T A Gudasheva, V V Grigoriev, K N Koliasnikova, V L Zamoyski, S B Seredenin
We have previously shown that neuropeptide cycloprolylglycine (CPG) increases the content of brain-derived neurotrophic factor (BDNF) in the culture of neuronal cells under normal conditions and in pathology. This is the first study to show that CPG at a physiological concentration of 10(-6) M significantly enhances the transmembrane AMPA currents in rat cerebellar Purkinje cells. Thus, CPG is a positive endogenous modulator of AMPA receptors. It was assumed that the neuropsychotropic effects of CPG are implemented as a result of BDNF accumulation after the activation of AMPA receptors by this neuropeptide...
November 2016: Doklady. Biochemistry and Biophysics
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