. An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP. Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9093-8. PubMed.


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  1. It’s fascinating to see that microRNAs are slowly but surely making their mark in neurobiology. This is very nice work by Gary Wayman and colleagues, further characterizing a novel signaling pathway implicating miR-132 in neuronal function (Vo et al., 2005). The current work is in line with previous studies demonstrating a role for specific microRNAs in synaptic development/plasticity (miR-134) and neuronal identity (miR-124) (Makeyev et al., 2007; Schratt et al., 2006).

    Here, the authors show that bicuculline, a compound that increases spontaneous synaptic activity and dendritic outgrowth in cultured neurons, induces miR-132 expression. This effect is dependent on the transcription factor CREB and implicates p250GAP as a downstream effector target of miR-132. Overall, they elegantly show that miR-132 is necessary for the bicuculline-induced effects on dendritic growth in hippocampal neurons.

    Along with the above-mentioned studies, this work supports the interesting possibility that dysregulation of microRNA pathways could contribute to a neurodegenerative (Hébert and De Strooper, 2007; Hébert et al., 2008) or psychiatric phenotype in humans (note that bicuculline is commonly used to study epilepsy). It has been known for a long time that synaptic dysfunction is tightly related to Alzheimer disease, for example. Thus, changes in this and possibly other signaling pathways may have profound effects on memory and AD pathology.

    While progressive neuronal loss is observed in post-mitotic neurons (including hippocampal neurons) of miRNA-deficient mice (Davis et al., 2008; Schaefer et al., 2007), it would be interesting to assess the biological role of miR-132, among others, in an in vivo context, either by gene knockout or by RNA knockdown.


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    View all comments by Sebastien S. Hebert

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  1. Research Brief: MicroRNA Ties Neuronal Activity to Dendritic Remodeling