Improved motor learning in adenosine A1 receptor knockout mice

Adenosine is a widespread neuromodulator, acting at A1 and A2A receptors in the brain. Adenosine plays role in a multitude of functions including sleep, homeostasis, neuroprotection and synaptic plasticity. Deletion of A1Rs in knock-out mice (A1R KO) revealed non-uniform effects on learning: learning sequential visual discrimination tasks was impaired, while spatial learning (Morris maze) and working memory tasks were not. Motor learning was also preserved in A1R KO mice. However, a systematic comparison of motor learning in KO and wild type (WT) mice has not been performed. Here we fill this knowledge gap by comparing motor learning in WT and A1R KO mice using an accelerating rotarod task. Both genotypes acquired motor skill and retained it after 1 week without further training. Genotype and Age had significant effects on improvement of motor skills relative to initial performance. A1R KO mice showed higher rate of learning than WT across training days, and reached better performance by the end of training (Day 5). However, retention after 1 week was better in WT mice, which improved relative to last day of training, while KO animals performed at the same level. We saw no differences between females and males, but older animals showed greater gains during learning and better retention. Finally, individual variability of motor learning was not related to measures of baseline motor activity, or anxiety. These results add new pieces to a multifaceted and intriguing picture of shifts in the brain functions resulting from A1R loss and warrant further exploration.