Download LARGE SCALE SCREENING OF miRNA EXPRESSION

INVOLVEMENT OF miRNA IN DIFFERENT BRAIN STRUCTURES AFTER SPATIAL
LEARNING IN MICE.
J. Camon1,2, V. Ferretti1,2, V. Licursi1, F. Capitano1, L. Maggi3, P. Fragapane4, C. Mannironi2,
S. Vincenti2, P. Paggi1, C. Presutti1 , A. Oliverio1,2 , R. Negri1 & A. Mele1,2
(1) Dept. Biol. and Biotech. Center for Res. in Neurobiol. D. Bovet Sapienza-Univ. Roma,
Rome, Italy; (2) Inst. Biol Cell e Neuroscienze CNR, Rome, Italy; (3) Dept. Human Fisiol and
Pharmacol, Rome, Italy; (4) Inst. Biol. Mol. Pat. CNR, Rome, Italy.
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.
Effects of miR icv administrations on spatial learning