INVOLVEMENT OF miRNA IN DIFFERENT BRAIN STRUCTURES AFTER SPATIAL LEARNING IN MICE
Formation of long-term memories (LTMs) is accomplished through structural changes of neurons leading to a rearrangement of the neural networks requiring both gene expression and protein synthesis. Evidence for local mRNAs and translational machineries at dendrites has suggested that post-transcriptional regulatory mechanisms at this level might be crucial in stabilization of LTMs. In particular microRNAs (miRs), small noncoding RNA, have been demonstrated to play a role in post-transcriptional gene regulation and brain plasticity, however, their possible involvement in learning and memory, to our knowledge has never been demonstrated.
The hippocampus and the ventral striatum are considered as key structures in the stabilization of spatial memories. Therefore, first we performed a large scale screening of miR expression in these two brain regions after spatial learning. CD1 mice were trained with a massed procedure in the spatial version of the Morris water maze. 1 hour after training, the hippocampus and the VS were dissected, the RNA extracted and miR expression assessed by way of the microarray technique. To study the spatial learning component, we compared miR expression profiles of mice submitted to the spatial procedure with those of mice exposed to the same context not required the use any spatial strategy.
The microarray analysis demonstrated: 1. Spatial learning induced changes in miR expression; 2. Distinct learning induced expression profiles in the two structures. Next, in order to verify whether miR had a causal role in the memorization process we over expressed a miR found changed in both the hippocampus and the VS and tested the animals for long term plasticity (long term potenziation-LTP) and memory. Treated mice showed impaired maintenance of hippocampal induced LTP and impaired ability to locate the correct quadrant in the spatial version of the Morris water maze (Figure). To our knowledge this is the first in vivo demonstration of the involvement of this non-coding miR in long term memory process.