miRNA-Dependent Control of Homeostatic Plasticity in Neurons

Abstract

Homeostatic plasticity is a form of plasticity in which neurons compensate for changes in neuronal activity through the control of key physiological parameters such as the number and the strength of their synaptic inputs and intrinsic excitability. Recent studies revealed that miRNAs, which are small non-coding RNAs repressing mRNA translation, participate in this process by controlling the translation of multiple effectors such as glutamate transporters, receptors, signaling molecules and voltage-gated ion channels. In this review, we present and discuss the role of miRNAs in both cell-wide and compartmentalized forms of homeostatic plasticity as well as their implication in pathological processes associated with homeostatic failure.

MDGAs are fast-diffusing molecules that delay excitatory synapse development by altering neuroligin behavior

“…One interesting factor might be constitutive neuronal activity that can influence synaptic protein expression levels, e.g. by modulating microRNAs 55, 56 . Indeed, MDGA1 transcripts were recently found to be upregulated in response to chronic synaptic activity blockade 57 .…”

MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation

“…MicroRNAs (miRNAs), which have the potential to post-transcriptionally silence hundreds of genes, are already known to modulate neurodevelopment (Petri et al, 2014;Sun and Shi, 2015) and neurodegeneration (Abe and Bonini, 2013;Ju zwik et al, 2019). Accordingly, specific miRNAs that regulate neuronal activity and synaptic function in established neurons have been identified (Dubes et al, 2019;Edbauer et al, 2010;Schratt et al, 2006;Siegert et al, 2015). However, whether there are miRNAs that are selectively induced and functionally important during postnatal brain maturation is unknown.…”

mir124-dependent tagging of glutamatergic synapses by synaptopodin controls non-uniform and input-specific homeostatic synaptic plasticity

“…4A) . This revealed the selective contribution of miRNAs according to the activity-deprivation paradigm (Dubes et al, 2019). Importantly, the drop in miR-124 levels induced by the TTX treatment was compatible with the increased expression of SP and GluA2-containing AMPARs at a subset of spines.…”

“…One possible mechanism supporting such synapse autonomy is local protein translation, a process that occurs in remote subcellular compartments including presynaptic terminals and dendritic spines (Hafner et al, 2019; Rangaraju et al, 2017; Wang et al, 2010) and which contributes to local forms of HSP, in particular by regulating the expression of the GluA1 subunit of AMPARs (Aoto et al, 2008; Ju et al, 2004; Letellier et al, 2014; Maghsoodi et al, 2008; Sutton et al, 2006). Among the actors that can regulate local protein translation, microRNAs (miRNAs) control various forms of HSP (Dubes et al, 2019; Fiore et al, 2014; Letellier et al, 2014; Mellios et al, 2011; Rajman et al, 2017; Silva et al, 2019; Tognini et al, 2011). These small noncoding RNAs hybridize to the 3’ UTR of multiple target mRNAs and inhibit protein synthesis through translational repression or destabilization of the transcripts (Filipowicz et al, 2008; Friedman et al, 2008; Soula et al, 2018).…”