The Department of Biomedicine

BBB seminar: Sonia Correa

The temporal dynamics of Arc expression regulate synaptic plasticity and learning behaviour

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Sonia Correa
School of Pharmacy and Medical Sciences, University of Bradford, UK

Neuronal activity regulates the transcription and translation of the immediate early gene Arc/Arg3.1, a key mediator of AMPA receptor trafficking and 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 knock-in 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 impairment was coupled to changes in Arc mRNA and protein expression resulting in a reduced threshold to induce metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) and enhanced mGluR-LTD amplitude. These findings show that the abnormal persistence of Arc protein limits the dynamic range of Arc signalling pathways specifically during reversal learning. Our work shows how the precise temporal control of activity-dependent molecules, such as Arc, regulates synaptic plasticity and is crucial for cognition.

Chairperson: Clive Bramham, Department of Biomedicine