Neuron · 2018 · 101 citations · 33 references
Life SciencesNeurobiologyNeuroscienceMolecular NeurobiologyMolecular NeuroscienceSynaptic PlasticityActivity-dependent PlasticityActivity-dependent Synaptic RemodelingLearning In Neural SystemsLong-term PotentiationSynaptic Strength RegulationSynaptic TransmissionActivity-dependent Synaptic ModificationImmediate Early GenesPersistenceProteasome-mediated DegradationReversal LearningTemporal DynamicsTemporal ExpressionTemporal Gene Expression
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.
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing.
PubMed · 1997 · 66.6K citations
Primer3Plus, an enhanced web interface to Primer3
Andreas Untergasser, Harm Nijveen, Xiancai Rao et al. · Nucleic Acids Research · 2007 · 2.9K citations · Full text