Regulation of miR-219 expression by experience and learning

Oligodendrocyte differentiation and myelin formation are processes that are fundamental to have rapid and efficient action potential propagation in the CNS. Myelin maturation happens in mice mostly in the first weeks of life and defects in this mechanism can bring to a premature death of the animals. Demyelination and failure in myelin repair are at the base of severe human pathologies such as Multiple Sclerosis. Acting as post-transciptional regulators, microRNAs are known to be involved in the modulation of many biological processes. Several of these small molecules seem to participate in oligodendrocyte development and myelination, and one of them in particular plays a fundamental role in these processes. miR-219, in fact, has been demonstrated to be both necessary to myelination in the CNS and sufficient to myelin repair after injury. Among known targets of this miRNA there are several oligodendrocyte differentiation inhibitors, so the current hypothesis is that miR-219 act as a promoter of oligodendrocyte lineage progression. Studies on miR-219 until now focused on its role during development and in pathological condition such as demyelinating injuries. Our objective was to expand the knowledge we have on this oligonucleotide in order to have a more comprehensive view of its action throughout all life. For this reason, the first thing we did was an expression study of this miRNA via real-time PCR on explants from mice of different ages. Recent works suggest that active myelination is necessary in adult mice to learn a motor task. It is also known that time of arrival of impulses at the synapses is an important factor for synaptic plasticity and that myelin sheaths have a central in the modulation of impulse transmission velocity, so it is reasonable to think that myelination could be involved in the processes underlying neural plasticity. Given these premises, we asked ourselves if miR-219 expression could be influenced by experience and learning of a task. To investigate this we did experiments interfering with normal visual experience in mice and then we verified the expression of miR-219 and of some of its targets in the visual cortex through real-time PCR. For example, we utilized a dark-rearing protocol to see if the delay in visual experience have an effect on miR-219 expression. Successively, we tested if miR-219 expression changes in a behavioural protocol of active learning, and we investigated consequences on myelination trough immunohistochemistry