miRNA-132: a dynamic regulator of cognitive capacity.
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.
Department of Neuroscience, Ohio State University, Graves Hall, Rm 4118, 333 W. 10th Ave, Columbus, OH 43210, USA.
Katelin F
KF
Hansen
Kate
K
Karelina
Kensuke
K
Sakamoto
Gary A
GA
Wayman
Soren
S
Impey
Karl
K
Obrietan
D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010364:Pattern Recognition, Visual / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013028:Space Perception / Q000502:physiology; D013997:Time Factors
C485182:Cyan Fluorescent Protein; C546976:MIRN132 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D011505:Protein-Tyrosine Kinases; D051058:Oncogene Protein v-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D004318:Doxycycline