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Review
. 2009;11(3):133-40.
doi: 10.1007/s12017-009-8065-2. Epub 2009 May 21.

microRNA regulation of synaptic plasticity

Neil R Smalheiser  1 , Giovanni Lugli
Affiliations
Review

microRNA regulation of synaptic plasticity

Neil R Smalheiser et al. Neuromolecular Med. 2009.

Abstract

microRNAs play an important role in regulating synaptic plasticity. For example, microRNAs target (and are targeted by) plasticity mediators such as CREB, MECP2, and FMRP. As well, specific microRNAs have been shown to be expressed within dendrites, where they regulate protein translation of targets mediating dendritic growth. Components of the RISC machinery have been implicated in long-term memory in Drosophila. Here, we review evidence from studies of adult mouse forebrain supporting a model wherein synaptic stimulation (above a threshold value) increases calcium within dendritic spines, activates calpain, and activates and releases dicer from the postsynaptic density. Dicer processes local pre-miRs into mature miRNAs that are incorporated into RISC complexes within or near the dendritic spine, and that bind available target mRNAs in the vicinity. These may repress protein translation under resting conditions, yet permit a phasic burst of translation to occur transiently following subsequent synaptic activity. Loaded RISC complexes that are not bound to local mRNAs may serve to bind and trap mRNAs that are being transported down dendrites. Thus, locally formed microRNAs may mark the location of previously activated synapses and perform a type of synaptic tagging and capture.

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Figures

Fig. 1
Fig. 1
Electron microscopic localization of dicer and eIF2c in dendritic spines in cortex and hippocampal area CA1. The distribution of dicer (a, c) tended to be more discrete than eIF2c (b). In the cortical spine in (c), a deposit of label can be seen surrounding the spine apparatus (arrow). Postsynaptic densities were heavily labeled for both proteins, much greater than the slight contrast due to heavy metal staining that can be seen in tissue labeled without the primary antibody (d). s spine head; at axon terminal. Scale bar = 200 nm. Reprinted from Lugli et al. (2005) by permission of Journal of Neurochemistry
Fig. 2
Fig. 2
Distribution of synaptosomal proteins and RNAs in soluble versus PSD fractions after extraction with Triton X-100. a Immuno-blotting. Total forebrain homogenate (T) was processed to obtain a soluble cytoplasmic fraction (S2) and a synaptosomal fraction (Sy) that was then lysed with 1% Triton X-100 to yield soluble (Ss) and PSD fractions (Sp). Equal amounts of protein were loaded and blotted for different antibodies as indicated. The dicer antibody was chicken polyclonal anti-dicer (Lugli et al. 2005). b qRT-PCR measurements of RNAs. Total RNA was prepared from Ss and Sp fractions and measured. The Sp/Sy ratio was calculated for three independent preps and is plotted as shown. microRNA precursors are shown in red, mature microRNAs in blue, and other RNAs in green. Reprinted from Lugli et al. (2008) by permission of Journal of Neurochemistry
Fig. 3
Fig. 3
Enrichment ratio (synaptoneurosomes/total homogenate) of various RNAs as measured by qRT-PCR. Data represent the average of three independent preps. microRNA precursors are shown in red, mature microRNAs in blue, and other RNAs in green. Reprinted from Lugli et al. (2008) by permission of Journal of Neurochemistry
Fig. 4
Fig. 4
Diagram of a microRNA small hairpin precursor (pre-miR). Shown is pre-miR-339. Zone 1 comprises the loop, zone 2 includes the region giving rise to the mature mir-339 sequence (shown in bold), and zone 3 includes sequences (if any) below the mature microRNA. Regions of bases connected by bonds (including G:U bonds) are referred to as stems, and opposing bases not connected by bonds are referred to as bulges. Reprinted from Smalheiser (2008b)
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References

    1. Abu-Elneel K, Liu T, Gazzaniga FS, Nishimura Y, Wall DP, Geschwind DH, et al. Heterogeneous dysregulation of microRNAs across the autism spectrum. Neurogenetics. 2008;9:153–161. - PubMed
    1. Asaki C, Usuda N, Nakazawa A, Kametani K, Suzuki T. Localization of translational components at the ultrami-croscopic level at postsynaptic sites of the rat brain. Brain Research. 2003;972:168–176. - PubMed
    1. Ashraf SI, McLoon AL, Sclarsic SM, Kunes S. Synaptic protein synthesis associated with memory is regulated by the RISC pathway in Drosophila . Cell. 2006;124:191–205. - PubMed
    1. Barco A, Lopez de Armentia M, Alarcon JM. Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited 10 years later. Neuroscience and Biobehavioral Reviews. 2008;32:831–851. - PubMed
    1. Beveridge NJ, Tooney PA, Carroll AP, Gardiner E, Bowden N, Scott RJ, et al. Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Human Molecular Genetics. 2008;17:1156–1168. - PubMed

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