Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility.

Neuron | 2018

Neuronal activity regulates the transcription and translation of the immediate-early gene Arc/Arg3.1, a key mediator of synaptic plasticity. Proteasome-dependent degradation of Arc tightly limits its temporal expression, yet the significance of this regulation remains unknown. We disrupted the temporal control of Arc degradation by creating an Arc knockin mouse (ArcKR) where the predominant Arc ubiquitination sites were mutated. ArcKR mice had intact spatial learning but showed specific deficits in selecting an optimal strategy during reversal learning. This cognitive inflexibility was coupled to changes in Arc mRNA and protein expression resulting in a reduced threshold to induce mGluR-LTD and enhanced mGluR-LTD amplitude. These findings show that the abnormal persistence of Arc protein limits the dynamic range of Arc signaling pathways specifically during reversal learning. Our work illuminates how the precise temporal control of activity-dependent molecules, such as Arc, regulates synaptic plasticity and is crucial for cognition.

Pubmed ID: 29861284 RIS Download

Research resources used in this publication

Associated grants

  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/H018344/1
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS085093
  • Agency: NINDS NIH HHS, United States
    Id: R00 NS076364
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH112766
  • Agency: Wellcome Trust, United Kingdom
  • Agency: NIGMS NIH HHS, United States
    Id: R25 GM089569
  • Agency: NIGMS NIH HHS, United States
    Id: R25 GM109442
  • Agency: NICHD NIH HHS, United States
    Id: T32 HD007491

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

View all literature mentions

Millipore (tool)

RRID:SCR_008983

An Antibody supplier

View all literature mentions

Applied Biosystems (tool)

RRID:SCR_005039

An Antibody supplier

View all literature mentions

NEURON (tool)

RRID:SCR_005393

NEURON is a simulation environment for modeling individual neurons and networks of neurons. It provides tools for conveniently building, managing, and using models in a way that is numerically sound and computationally efficient. It is particularly well-suited to problems that are closely linked to experimental data, especially those that involve cells with complex anatomical and biophysical properties. NEURON has benefited from judicious revision and selective enhancement, guided by feedback from the growing number of neuroscientists who have used it to incorporate empirically-based modeling into their research strategies. NEURON's computational engine employs special algorithms that achieve high efficiency by exploiting the structure of the equations that describe neuronal properties. It has functions that are tailored for conveniently controlling simulations, and presenting the results of real neurophysiological problems graphically in ways that are quickly and intuitively grasped. Instead of forcing users to reformulate their conceptual models to fit the requirements of a general purpose simulator, NEURON is designed to let them deal directly with familiar neuroscience concepts. Consequently, users can think in terms of the biophysical properties of membrane and cytoplasm, the branched architecture of neurons, and the effects of synaptic communication between cells. * helps users focus on important biological issues rather than purely computational concerns * has a convenient user interface * has a user-extendable library of biophysical mechanisms * has many enhancements for efficient network modeling * offers customizable initialization and simulation flow control * is widely used in neuroscience research by experimentalists and theoreticians * is well-documented and actively supported * is free, open source, and runs on (almost) everything

View all literature mentions

SPIKE (tool)

RRID:SCR_010466

Database of curated human signaling pathways with an associated interactive software tool for analysis and dynamic visualization of pathways. Individual pathway maps can be viewed and downloaded; the entire database may be browsed, or launched via a map viewer tool that allows dynamic visualization of the database and save networks in XGMML format that can be viewed in all generic XGMML viewers. Map Topics * Cell cycle progress and check points * DNA damage response * Programmed cell death related processes * Stress-activated transcription factors * Mitogen-activated protein kinase pathways * Immune response signaling * HEarSpike: hearing related pathways

View all literature mentions

Jackson ImmunoResearch (tool)

RRID:SCR_010488

A commercial antibody vendor, specializing in secondary antibodies.

View all literature mentions

Synaptic Systems (tool)

RRID:SCR_013612

An Antibody supplier

View all literature mentions

C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions

BALB/cAnNCrl (tool)

RRID:MGI:2683685

laboratory mouse with name BALB/cAnNCrl from MGI.

View all literature mentions

C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions

Peroxidase AffiniPure Goat Anti-Mouse IgG, light chain specific (antibody)

RRID:AB_2338512

This polyclonal secondary targets IgG, Light Chain Specific

View all literature mentions

Anti-rabbit IgG, HRP-linked Antibody (antibody)

RRID:AB_2099233

This polyclonal secondary targets IgG

View all literature mentions

IRDye 800CW Goat anti-Rabbit IgG (antibody)

RRID:AB_621843

This polyclonal secondary targets IgG

View all literature mentions

beta Actin antibody [GT5512] (antibody)

RRID:AB_2728646

This monoclonal targets beta Actin

View all literature mentions

Anti-PSD 95 (antibody)

RRID:AB_887760

This polyclonal targets PSD 95

View all literature mentions

NMDAepsilon2 (C-20) (antibody)

RRID:AB_670229

This polyclonal targets GRIN2B

View all literature mentions

NMDAzeta1 (C-20) (antibody)

RRID:AB_670215

This polyclonal targets GRIN1

View all literature mentions

Rabbit Anti-Metabotropic Glutamate Receptor 5 (mGluR5) , Unconjugated (antibody)

RRID:AB_2295173

This polyclonal targets Metabotropic Glutamate Receptor 5 (mGluR5)

View all literature mentions

Rabbit Anti-Glutamate Receptor 1A, Metabotropic (mGluR1A) Antibody, Unconjugated (antibody)

RRID:AB_259995

This unknown targets Glutamate Receptor 1A, Metabotropic (mGluR1A)

View all literature mentions

Anti-GluR1-NT (NT) Antibody, clone RH95 (antibody)

RRID:AB_11212678

This monoclonal targets GluR1, N Terminus

View all literature mentions

GAPDH antibody [6C5] (antibody)

RRID:AB_2107448

This monoclonal targets GAPDH antibody [6C5]

View all literature mentions

Anti-Arc (antibody)

RRID:AB_887694

This polyclonal targets Arc

View all literature mentions

Fiji (software resource)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

View all literature mentions

ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

View all literature mentions

Spike2 Software (software resource)

RRID:SCR_000903

THIS RESOURCE IS NO LONGER IN SERVICE.Documented on September 23,2022. A data acquisition and analysis software package for electrophysiology data. Spike2 software offers multi-channel continuous data acquisition and analysis with a multitude of options. This offers flexible usage from a simple chart recorder to complex applications requiring stimulus generation, data capture, scrolling or triggered displays, control of external equipment, and custom analysis. Spike2 software can be used in many fields such as electrophysiology, neurophysiology, cardiovascular and respiratory studies, sports science and pharmacology.

View all literature mentions

Mini Analysis Program (software resource)

RRID:SCR_002184

Software tool that detects peaks of any type, any shape, any direction, and any size for neuroscientists who are studying spontaneous activities. Allows detection of virtually any kind of peaks including spontaneous miniature synaptic currents and potentials, action potential spikes, calcium imaging peaks, amperometric peaks, ECG peaks etc. It includes the complex and multiple peak detection algorithm. Has post-detection analyses including essential plots and statistical parameters. Group Analysis provides specialized and detailed analysis options for action potentials, decay fitting, fEPSP/population spikes, amperometry, etc.

View all literature mentions

pClamp (software resource)

RRID:SCR_011323

Software suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.

View all literature mentions

Microcal Origin (software resource)

RRID:SCR_002815

A complete graphing and data analysis software package that provides a suite of features catering to the needs of scientists and engineers. Main features: * Drag-and-drop import of data and images * Save import settings to a worksheet or external files for repeated use * Use saved settings to re-import files with a single click * Post-process imported data * Import Wizard with visual feedback * Handle non-standard files by programming

View all literature mentions

ANY-maze (software resource)

RRID:SCR_014289

Video tracking system used to automate testing in a variety of behavioral apparatus. ANY-maze can automatically track the tail, head, or body of a test animal in up to 16 pieces of apparatus. The software can record live images or digital files with different camera types and save the data in multiple formats. ANY-maze contains built in statistical tests and standard measures for distance, speed, mobility, duration, etc.

View all literature mentions

Primer3Plus (software resource)

RRID:SCR_003081

A web interface to the Primer3 primer design program as an enhanced alternative for the CGI- scripts that come with Primer3.

View all literature mentions

Fiji (software resource)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

View all literature mentions

ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

View all literature mentions

Spike2 Software (software resource)

RRID:SCR_000903

THIS RESOURCE IS NO LONGER IN SERVICE.Documented on September 23,2022. A data acquisition and analysis software package for electrophysiology data. Spike2 software offers multi-channel continuous data acquisition and analysis with a multitude of options. This offers flexible usage from a simple chart recorder to complex applications requiring stimulus generation, data capture, scrolling or triggered displays, control of external equipment, and custom analysis. Spike2 software can be used in many fields such as electrophysiology, neurophysiology, cardiovascular and respiratory studies, sports science and pharmacology.

View all literature mentions

Mini Analysis Program (software resource)

RRID:SCR_002184

Software tool that detects peaks of any type, any shape, any direction, and any size for neuroscientists who are studying spontaneous activities. Allows detection of virtually any kind of peaks including spontaneous miniature synaptic currents and potentials, action potential spikes, calcium imaging peaks, amperometric peaks, ECG peaks etc. It includes the complex and multiple peak detection algorithm. Has post-detection analyses including essential plots and statistical parameters. Group Analysis provides specialized and detailed analysis options for action potentials, decay fitting, fEPSP/population spikes, amperometry, etc.

View all literature mentions

pClamp (software resource)

RRID:SCR_011323

Software suite for electrophysiology data acquisition and analysis by Molecular Devices. Used for the control and recording of voltage clamp, current clamp, and patch clamp experiments. The software suite consists of Clampex 11 Software for data acquisition, AxoScope 11 Software for background recording, Clampfit 11 Software for data analysis, and optional Clampfit Advanced Analysis Module for sophisticated and streamlined analysis.

View all literature mentions

Microcal Origin (software resource)

RRID:SCR_002815

A complete graphing and data analysis software package that provides a suite of features catering to the needs of scientists and engineers. Main features: * Drag-and-drop import of data and images * Save import settings to a worksheet or external files for repeated use * Use saved settings to re-import files with a single click * Post-process imported data * Import Wizard with visual feedback * Handle non-standard files by programming

View all literature mentions

ANY-maze (software resource)

RRID:SCR_014289

Video tracking system used to automate testing in a variety of behavioral apparatus. ANY-maze can automatically track the tail, head, or body of a test animal in up to 16 pieces of apparatus. The software can record live images or digital files with different camera types and save the data in multiple formats. ANY-maze contains built in statistical tests and standard measures for distance, speed, mobility, duration, etc.

View all literature mentions

Peroxidase AffiniPure Goat Anti-Mouse IgG, light chain specific (antibody)

RRID:AB_2338512

This polyclonal secondary targets IgG, Light Chain Specific

View all literature mentions

Anti-rabbit IgG, HRP-linked Antibody (antibody)

RRID:AB_2099233

This polyclonal secondary targets IgG

View all literature mentions

IRDye 800CW Goat anti-Rabbit IgG (antibody)

RRID:AB_621843

This polyclonal secondary targets IgG

View all literature mentions

beta Actin antibody [GT5512] (antibody)

RRID:AB_2728646

This monoclonal targets beta Actin

View all literature mentions

Anti-PSD 95 (antibody)

RRID:AB_887760

This polyclonal targets PSD 95

View all literature mentions

NMDAepsilon2 (C-20) (antibody)

RRID:AB_670229

This polyclonal targets GRIN2B

View all literature mentions

NMDAzeta1 (C-20) (antibody)

RRID:AB_670215

This polyclonal targets GRIN1

View all literature mentions

Rabbit Anti-Metabotropic Glutamate Receptor 5 (mGluR5) , Unconjugated (antibody)

RRID:AB_2295173

This polyclonal targets Metabotropic Glutamate Receptor 5 (mGluR5)

View all literature mentions

Rabbit Anti-Glutamate Receptor 1A, Metabotropic (mGluR1A) Antibody, Unconjugated (antibody)

RRID:AB_259995

This unknown targets Glutamate Receptor 1A, Metabotropic (mGluR1A)

View all literature mentions

Anti-GluR1-NT (NT) Antibody, clone RH95 (antibody)

RRID:AB_11212678

This monoclonal targets GluR1, N Terminus

View all literature mentions

GAPDH antibody [6C5] (antibody)

RRID:AB_2107448

This monoclonal targets GAPDH antibody [6C5]

View all literature mentions

Anti-Arc (antibody)

RRID:AB_887694

This polyclonal targets Arc

View all literature mentions