Spatial memory and plasticity: molecular mechanisms in the hippocampus and the ventral striatum

Formation of long-term memories (LTM) is accomplished through structural changes of neurons leading to a rearrangement of the neural networks requiring 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 also be crucial in the stabilization of LTM. In particular microRNAs (miRs), small noncoding molecules, have been demonstrated a role in post-transcriptional gene regulation. The hippocampus and the ventral striatum (VS) are considered as key structures in the stabilization of spatial memories. In order to shade light on molecular processes underlying such stabilization during my PhD we performed a large scale screening of miR and mRNAs expression in these two brain regions after spatial learning. CD1 mice were trained with a massed procedure in the spatial version of the water maze. 1 hour after training, the hippocampus and the VS were dissected and RNA extracted. 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 but without require the application of a spatial strategy. The results of microarray analysis showed modification in miR and mRNA expression levels, both up and down-regulation, in both brain structures after learning. To verify a possible causal relationship between miRs and experience dependent plasticity we overexpressed, learning downregulated miR, before training in water maze. Mimic but not scramble injected mice showed impaired ability to locate the correct quadrant on the probe test. Our results demonstrate for the first time in vivo, the importance of miRs regulation in long-term memory processes. Interestingly, spatial learning induced profile of both miR and mRNA expression varied between the two structures. Thus suggesting that different molecular mechanisms might underlie learning induced plasticity in different brain areas.