Category Archives: J Neurosci

Exchange Protein Directly Activated by cAMP (EPAC) Regulates Neuronal Polarization through Rap1B.

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Exchange Protein Directly Activated by cAMP (EPAC) Regulates Neuronal Polarization through Rap1B.

J Neurosci. 2015 Aug 12;35(32):11315-29

Authors: Muñoz-Llancao P, Henríquez DR, Wilson C, Bodaleo F, Boddeke EW, Lezoualc’h F, Schmidt M, González-Billault C

Abstract
UNLABELLED: Acquisition of neuronal polarity is a complex process involving cellular and molecular events. The second messenger cAMP is involved in axonal specification through activation of protein kinase A. However, an alternative cAMP-dependent mechanism involves the exchange protein directly activated by cAMP (EPAC), which also responds to physiological changes in cAMP concentration, promoting activation of the small Rap GTPases. Here, we present evidence that EPAC signaling contributes to axon specification and elongation. In primary rat hippocampal neurons, EPAC isoforms were expressed differentially during axon specification. Furthermore, 8-pCPT, an EPAC pharmacological activator, and genetic manipulations of EPAC in neurons induced supernumerary axons indicative of Rap1b activation. Moreover, 8-pCPT-treated neurons expressed ankyrin G and other markers of mature axons such as synaptophysin and axonal accumulation of vGLUT1. In contrast, pharmacological inhibition of EPAC delayed neuronal polarity. Genetic manipulations to inactivate EPAC1 using either shRNA or neurons derived from EPAC1 knock-out (KO) mice led to axon elongation and polarization defects. Interestingly, multiaxonic neurons generated by 8-pCPT treatments in wild-type neurons were not found in EPAC1 KO mice neurons. Altogether, these results propose that EPAC signaling is an alternative and complementary mechanism for cAMP-dependent axon determination.
SIGNIFICANCE STATEMENT: This study identifies the guanine exchange factor responsible for Rap1b activation during neuronal polarization and provides an alternate explanation for cAMP-dependent acquisition of neuronal polarity.

PMID: 26269639 [PubMed – in process]

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Linkage Analysis in a Dutch Population Isolate Shows No Major Gene for Left-Handedness or Atypical Language Lateralization.

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Linkage Analysis in a Dutch Population Isolate Shows No Major Gene for Left-Handedness or Atypical Language Lateralization.
J Neurosci. 2015 Jun 10;35(23):8730-6
Authors: Somers M, Ophoff RA, Aukes MF… Continue reading

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Improvement in Visual Search with Practice: Mapping Learning-Related Changes in Neurocognitive Stages of Processing.

Improvement in Visual Search with Practice: Mapping Learning-Related Changes in Neurocognitive Stages of Processing.
J Neurosci. 2015 Apr 1;35(13):5351-5359
Authors: Clark K, Appelbaum LG, van den Berg B, Mitroff SR,… Continue reading

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Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss.

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss.

J Neurosci. 2014 Nov 19;34(47):15715-15721

Authors: Havekes R, Bruinenberg VM, Tudor JC, Ferri SL, Baumann A, Meerlo P, Abel T

Abstract
The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation.

PMID: 25411499 [PubMed – as supplied by publisher]

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Glutamatergic signaling at the vestibular hair cell calyx synapse.

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Glutamatergic signaling at the vestibular hair cell calyx synapse.
J Neurosci. 2014 Oct 29;34(44):14536-50
Authors: Sadeghi SG, Pyott SJ, Yu Z, Glowatzki E
Abstract
In the vestibular p… Continue reading

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Transduction without tip links in cochlear hair cells is mediated by ion channels with permeation properties distinct from those of the mechano-electrical transducer channel.

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Transduction without tip links in cochlear hair cells is mediated by ion channels with permeation properties distinct from those of the mechano-electrical transducer channel.
J Neurosci. 2014 Apr 16;34(16):5… Continue reading

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Dorsal root ganglion neurons carrying a P301S Tau mutation: a valid in vitro model for screening drugs against tauopathies?

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Dorsal root ganglion neurons carrying a P301S Tau mutation: a valid in vitro model for screening drugs against tauopathies?
J Neurosci. 2014 Apr 2;34(14):4757-9
Authors: Alberts N, Groen K, Klein L, … Continue reading

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Decoupling interval timing and climbing neural activity: a dissociation between CNV and N1P2 amplitudes.

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Decoupling interval timing and climbing neural activity: a dissociation between CNV and N1P2 amplitudes.

J Neurosci. 2014 Feb 19;34(8):2931-9

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Systematic Regional Variations of GABA, Glutamine, and Glutamate Concentrations Follow Receptor Fingerprints of Human Cingulate Cortex.

Systematic Regional Variations of GABA, Glutamine, and Glutamate Concentrations Follow Receptor Fingerprints of Human Cingulate Cortex.

J Neurosci. 2013 Jul 31;33(31):12698-12704

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The relation between perception and brain activity in gaze-evoked tinnitus.

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The relation between perception and brain activity in gaze-evoked tinnitus.

J Neurosci. 2012 Dec 5;32(49):17528-39

Authors: van Gendt MJ, Boyen K, de…

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Phosphorylation of AMPA-Type Glutamate Receptors: The Trigger of Epileptogenesis?

Phosphorylation of AMPA-Type Glutamate Receptors: The Trigger of Epileptogenesis?

J Neurosci. 2013 Apr 3;33(14):5879-80

Authors: Bakker J, Basedow FJ, Dekker AD, Papantoniou C

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Action Simulation Plays a Critical Role in Deceptive Action Recognition.

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Action Simulation Plays a Critical Role in Deceptive Action Recognition.

J Neurosci. 2013 Jan 9;33(2):611-623

Authors: Tidoni E, Borgomaneri S, di…

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Hearing an illusory vowel in noise: suppression of auditory cortical activity.

Hearing an illusory vowel in noise: suppression of auditory cortical activity.

J Neurosci. 2012 Jun 6;32(23):8024-34

Authors: Riecke L, Vanbussel M, Hausfeld L, Baskent D,…

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Yet Another Role for SIRT1: Reduction of α-Synuclein Aggregation in Stressed Neurons.

Yet Another Role for SIRT1: Reduction of α-Synuclein Aggregation in Stressed Neurons.
J Neurosci. 2012 May 9;32(19):6413-4
Authors: Oosterhof N, Dekens DW, Lawerman TF, van Dijk M
PMID: 22573663 [PubMed – in process]

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{micro}-Suppression during Action Observation and Execution Correlates with BOLD in Dorsal Premotor, Inferior Parietal, and SI Cortices.

{micro}-Suppression during Action Observation and Execution Correlates with BOLD in Dorsal Premotor, Inferior Parietal, and SI Cortices.

J Neurosci. 2011 Oct 5;31(40):14243-9

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