Journal article
miRNA-132: a dynamic regulator of cognitive capacity
Brain structure & function, Vol.218(3), pp.817-831
05/2013
Handle:
https://hdl.handle.net/2376/111186
PMCID: PMC3508255
PMID: 22706759
Abstract
Within the central nervous system, microRNAs have emerged as important effectors of an array of developmental, physiological, and cognitive processes. Along these lines, the CREB-regulated microRNA miR-132 has been shown to influence neuronal maturation via its effects on dendritic arborization and spinogenesis. In the mature nervous system, dysregulation of miR-132 has been suggested to play a role in a number of neurocognitive disorders characterized by aberrant synaptogenesis. However, little is known about the inducible expression and function of miR-132 under normal physiological conditions in vivo. Here, we begin to explore this question within the context of learning and memory. Using in situ hybridization, we show that the presentation of a spatial memory task induced a significant ~1.5-fold increase in miR-132 expression within the CA1, CA3, and GCL excitatory cell layers of the hippocampus. To examine the role of miR-132 in hippocampal-dependent learning and memory, we employ a doxycycline-regulated miR-132 transgenic mouse strain to drive varying levels of transgenic miR-132 expression. These studies revealed that relatively low levels of transgenic miR-132 expression, paralleling the level of expression in the hippocampus following a spatial memory task, significantly enhanced cognitive capacity. In contrast, higher (supra-physiological) levels of miR-132 (>3-fold) inhibited learning. Interestingly, both the impaired cognition and elevated levels of dendritic spines resulting from supra-physiological levels of transgenic miR-132 were reversed by doxycycline suppression of transgene expression. Together, these data indicate that miR-132 functions as a key activity-dependent regulator of cognition, and that miR-132 expression must be maintained within a limited range to ensure normal learning and memory formation.
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Details
- Title
- miRNA-132: a dynamic regulator of cognitive capacity
- Creators
- Katelin F Hansen - Department of Neuroscience, Ohio State University, Graves Hall, Rm 4118, 333 W. 10th Ave, Columbus, OH 43210, USAKate Karelina - Department of Neuroscience, Ohio State University, Graves Hall, Rm 4118, 333 W. 10th Ave, Columbus, OH 43210, USAKensuke Sakamoto - Department of Neuroscience, Ohio State University, Graves Hall, Rm 4118, 333 W. 10th Ave, Columbus, OH 43210, USAGary A Wayman - Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, USASoren Impey - Oregon Stem Cell Center, Oregon Health and Science University, Portland, OR, USAKarl Obrietan - Department of Neuroscience, Ohio State University, Graves Hall, Rm 4118, 333 W. 10th Ave, Columbus, OH 43210, USA
- Publication Details
- Brain structure & function, Vol.218(3), pp.817-831
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Grant note
- R01 NS067409 || NS / National Institute of Neurological Disorders and Stroke : NINDS R01 NS066345 || NS / National Institute of Neurological Disorders and Stroke : NINDS F31 MH096460 || MH / National Institute of Mental Health : NIMH R01 MH062335 || MH / National Institute of Mental Health : NIMH P30 NS045758 || NS / National Institute of Neurological Disorders and Stroke : NINDS
- Identifiers
- 99900547347201842
- Language
- English
- Resource Type
- Journal article