MicroRNAs and synaptic plasticity—a mutual relationship

Abstract

MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain-and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.

Role of miR-145 in chronic constriction injury in rats

“…In addition, effective diagnosis and treatment targets for neuropathic pain are lacking. It is reported that miRNA molecules are important regulatory factors in the nervous system and are extensively involved in various physiological and pathological activities of the nervous system, such as memory, neural remodeling and neurodegenerative changes (21).…”

MicroRNAs in neural development: from master regulators to fine-tuners

“…miR-134, miR-383, miR-382, miR-182) (Cheng et al, 2014) miR-199a (Tsujimura et al, 2015) miRNAs in the activity-dependent maturation of neural circuits, a form of developmental synaptic plasticity, in the mammalian brain in vivo. Further evidence for a role of miRNAs in synaptic plasticity, both during development and in adults, has been provided in recent years (reviewed by Aksoy-Aksel et al, 2014;Olde Loohuis et al, 2012;Wang et al, 2012;Ye et al, 2016), underscoring the importance of miRNAs in correct neural circuit formation, maturation and function.…”

“…In recent years, evidence for an important role of miRNAs in adult synaptic plasticity and cognition is also accumulating. However, these studies are not the focus of this Review, and we refer the reader to recent reviews on this subject (Aksoy-Aksel et al, 2014;Olde Loohuis et al, 2012;Wang et al, 2012;Ye et al, 2016).…”

Turing Revisited: Decoding the microRNA Messages in Brain Extracellular Vesicles for Early Detection of Neurodevelopmental Disorders

“…Karpova et al in a review focused on the epigenetic control of the brain-derived neurotrophic factor (BDNF), a central player in neuronal plasticity, reported that miRNAs, such as miR-206, targeted BDNF transcripts resulting in memory impairment and were up-regulated in neurodegenerative disorders [129]. Several reviews summarize the regulatory mechanisms of miRNAs in synaptic plasticity and learning memory and the picture that emerges is that miRNAs are ideally suited to contribute to the regulation of long-term potentiation-related gene expression, that miRNAs are pleiotropic, synaptically located, tightly regulated, and function in response to synaptic activity [130]–[133]. The first direct links between miRNA dysfunction and synaptic pathologies are emerging, raising the interest in these molecules as potential biomarkers and therapeutic targets in NDD.…”