U1 snRNA over-expression affects neural oscillations and short-term memory deficits in mice

Small nuclear RNAs (snRNAs) and other RNA spliceosomal components are involved in neurological and psychiatric disorders. U1 snRNA has recently been demonstrated to be altered in pathology in some neurodegenerative diseases, but whether it has a causative role is not clear. Here we have studied this by overexpressing U1 snRNA in mice and measured their hippocampal oscillatory patterns and brain functions. Novel object recognition test showed that the recognition index was significantly decreased in the U1 snRNA over-expression mice compared to that in the C57BL mice. U1 snRNA over-expression regulated not only the pattern of neural oscillations but also the expression of neuron excitatory and inhibitory proteins. Here we show that U1 snRNA over-expression contains the shrinkage distribution of theta-power, theta-phase lock synchronization, and theta and low-gamma cross-frequency coupling in the hippocampus. The alternations of neuron receptors by the U1 snRNA overexpression also modulated the decreasing of recognition index, the energy distribution of theta power spectrum with the reductions of theta phase synchronization and phase-amplitude coupling between theta and low-gamma. Linking these all together, our results suggest that U1 snRNA overexpression particularly causes a deficit in short-term memory. These findings make a bedrock of our research that U1 snRNA bridges the gap about the mechanism behind short-term memory based on the molecular and mesoscopic level.