Learning requires the chemical adaptation of individual synapses. Researchers have now revealed the impact of an RNA-binding protein that is intimately involved in this process on learning and memory formation and learning processes.
The formation of memories requires subtle changes in brain structures. This is because learning and memory are the result of the incessant modification of synapses – which provide the functional connections that enable nerve cells to communicate with one another. The long-term molecular alterations involved in this process are encoded by so-called messenger RNAs, which are produced in the nucleus of the neuron and must be transported to the appropriate synapses in order to program the synthesis of specific proteins “on-site”. In previous studies, Ludwig-Maximilians-Universitaet (LMU) in Munich scientist Michael Kiebler has shown that the RNA-binding protein Staufen2 plays an essential role in conveying these mRNAs to their destinations. But exactly how this molecular process actually affects learning and behavior was not well understood. Now, a study carried out by the Kiebler group, in collaboration with Dusan Bartsch (Mannheim University) and Spanish colleagues (Seville University), has shed new light on this issue. The new work shows, for the first time, that reduced levels of Staufen2 are associated with a specific impairment of memory. The findings appear in the journal Genome Biology.
The researchers made use of a genetic rat model that has been developed and refined over the past decade, in which the synthesis of Staufen2 can be conditionally and selectively suppressed in nerve cells in the forebrain. They then characterized the effects of reduced levels of Staufen2 protein on memory using behavioral tests that measure the efficacy of spatial, temporal and associative memory. These tasks are known to depend on synaptic plasticity, i.e. the ability to actively adjust the efficiency of communication between specific synaptic networks, in the hippocampus. The results clearly show that the reduction of Staufen2 in the forebrain has a negative impact on several aspects of memory. “Overall, long-term memory continues to function, and the rats remain capable of learning how to find a food source, for instance” – Kiebler says – “but when the mutants are asked to recall what they have learned after longer periods of time, their performance is significantly worse than wild-type animals.”