Role of CTRP14/C1QL1 in motor coordination and learning across the lifespan

Abstract

C1q/TNF-related protein 14 (CTRP14), also known as C1q-like 1 (C1QL1), is a synaptic protein predominantly expressed in the brain. It plays a critical role in the formation and maintenance of the climbing fiber-Purkinje cell synapses, ensuring that only one single winning climbing fiber from the inferior olivary neuron synapses with the proximal dendrites of Purkinje cells during the early postnatal period. Loss of CTRP14/C1QL1 results in incomplete elimination of supernumerary climbing fibers, leading to multiple persistent climbing fibers synapsing with the Purkinje cells. While this deficit impairs oculomotor learning in adult mice, the impact of CTRP14 deficiency on motor function throughout adulthood has not been examined. Here, we conduct behavioral tests on a constitutive Ctrp14 knockout (KO) mouse model to determine whether CTRP14 is required for motor learning and function in mice across the lifespan. We show that CTRP14 deficiency does not affect grip strength, nor sprint and endurance running, in young and old mice of either sex. We performed accelerated rotarod tests on mice at 6, 12, and 18 months old to assess motor coordination and learning. No significant differences were observed between WT and Ctrp14-KO mice of either sex across the lifespan. Lastly, we performed complex running wheel tests to detect latent motor deficits and found that aged Ctrp14-KO mice have intact motor skills. Despite some limitations of the study, our data suggest that CTRP14 is dispensable for gross motor skills, coordination, and learning throughout adulthood based on the specific tests performed.