HippocampalEgr1-Dependent Neuronal EnsemblesNegatively Regulate Motor Learning

Motor skills learning is classically associated with brain regions including cerebral and cerebellar cortices and basal ganglianuclei. Less is known about the role of the hippocampus in the acquisition and storage of motor skills. Here, we show thatmice receiving a long-term training in the accelerating rotarod display marked hippocampal transcriptional changes andreduced pyramidal neurons activity in the CA1 region when compared with naive mice. Then, we use mice in which neuralensembles are permanently labeled in anEgr1activity-dependent fashion. Using these mice, we identify a subpopulation ofEgr1-expressing pyramidal neurons in CA1 activated in short-term (STT) and long-term (LTT) trained mice in the rotarodtask. WhenEgr1is downregulated in the CA1 or these neuronal ensembles are depleted, motor learning is improved whereastheir chemogenetic stimulation impairs motor learning performance. Thus,Egr1organizes specific CA1 neuronal ensemblesduring the accelerating rotarod task that limit motor learning. These evidences highlight the role of the hippocampus in thecontrol of this type of learning and we provide a possible underlying mechanism