Essential role of the mouse synapse associated protein Syap1 in circuits for spontaneous motor activity and rotarod balance

Abstract

Synapse-associated protein 1 (Syap1) is the mammalian homologue of synapse-associated protein of 47 kDa (Sap47) in Drosophila. Genetic deletion of Sap47 leads to deficiencies in short-term plasticity and associative memory processing in flies. In mice, Syap1 is prominently expressed in the nervous system, but its function is still unclear. We have generated Syap1 knockout mice and tested motor behaviour and memory. These mice are viable and fertile but display distinct deficiencies in motor behaviour. Locomotor activity specifically appears to be reduced in early phases when voluntary movement is initiated. On the rotarod, a more demanding motor test involving control by sensory feedback, Syap1-deficient mice dramatically fail to adapt to accelerated speed or to a change in rotation direction. Syap1 is highly expressed in cerebellar Purkinje cells and cerebellar nuclei. Thus, this distinct motor phenotype could be due to a so far unknown function of Syap1 in cerebellar sensorimotor control. The observed motor defects are highly specific since other tests in the modified SHIRPA test, as well as cognitive tasks like novel object recognition, Pavlovian fear conditioning, and anxiety-like behaviour in open field, dark-light transition, and elevated plus maze, do not appear to be strongly affected in Syap1 knockout mice. Summary statement Knockout of the Syap1 gene in mice causes a distinct motor behaviour phenotype.