Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome

Learning and Memory

Volumn 23, Issue 2, 2016, Pages 61-71

  Hansen, Katelin F ^a   Sakamoto, Kensuke ^a   Aten, Sydney ^b   Snider, Kaitlin H ^b   Loeser, Jacob ^a   Hesse, Andrea M ^a   Page, Chloe E ^b   Pelz, Carl ^c   Simon, J ^c   Arthur, C ^a   Impey, Soren ^a   Obrietan, Karl ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

MICRORNA; MICRORNA 132; MICRORNA 212; TRANSCRIPTOME; UNCLASSIFIED DRUG; ASCL1 PROTEIN, MOUSE; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; MIRN132 MICRORNA, MOUSE; MIRN212 MICRORNA, MOUSE; STX1A PROTEIN, MOUSE; SYNTAXIN 1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL PROLIFERATION; COGNITIVE DEFECT; CONTROLLED STUDY; GENE DELETION; GENE EXPRESSION; GENE INACTIVATION; GENE LOCUS; GENE ONTOLOGY; GENE SEQUENCE; GENE TARGETING; GENETIC ANALYSIS; LEARNING; MEMORY; MEMORY DISORDER; MORPHOGENESIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; RECOGNITION; SPATIAL MEMORY; SYNAPTIC TRANSMISSION; ANIMAL; C57BL MOUSE; FOREBRAIN; GENE EXPRESSION PROFILING; GENETICS; HIPPOCAMPUS; KNOCKOUT MOUSE; METABOLISM; NERVE CELL; PHYSIOLOGY;

ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; GENE EXPRESSION PROFILING; HIPPOCAMPUS; MEMORY; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICRORNAS; NEURONS; PROSENCEPHALON; RECOGNITION (PSYCHOLOGY); SPATIAL MEMORY; SYNTAXIN 1; TRANSCRIPTOME;

EID: 84958743178     PISSN: 10720502     EISSN: 15495485     Source Type: Journal    
DOI: 10.1101/lm.039578.115     Document Type: Article

References (96)

1. Abdelmohsen K, Hutchison ER, Lee EK, Kuwano Y, Kim MM, Masuda K, Srikantan S, Subaran SS, Marasa BS, Mattson MP, et al. 2010. miR-375 inhibits differentiation of neurites by lowering HuD levels. Mol Cell Biol 30: 4197-4210.
2. Aguirre AA, Chittajallu R, Belachew S, Gallo V. 2004. NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus. J Cell Biol 165: 575-589.
3. Anders S, Huber W. 2010. Differential expression analysis for sequence count data. Genome Biol 11: R106.
4. Bennett MK, Calakos N, Scheller RH. 1992. Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 257: 255-259.
5. Betel D, Wilson M, Gabow A, Marks DS, Sander C. 2008. The microRNA.org resource: targets and expression. Nucleic Acids Res 36: D149-D153.
6. Bevins RA, Besheer J. 2006. Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study recognition memory. Nat Protoc 1: 1306-1311.
7. Breving K, Esquela-Kerscher A. 2010. The complexities of microRNA regulation: mirandering around the rules. Int J Biochem Cell Biol 42: 1316-1329.
8. Burgos K, Malenica I, Metpally R, Courtright A, Rakela B, Beach T, Shill H, Adler C, Sabbagh M, Villa S, et al. 2014. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimers and Parkinsons diseases correlate with disease status and features of pathology. PLoS One 9: e94839.
9. Chan JP, Cordeira J, Calderon GA, Iyer LK, Rios M. 2008. Depletion of central BDNF in mice impedes terminal differentiation of new granule neurons in the adult hippocampus. Mol Cell Neurosci 39: 372-383.
10. Choi SH, Li Y, Parada LF, Sisodia SS. 2009. Regulation of hippocampal progenitor cell survival, proliferation and dendritic development by BDNF. Mol Neurodegener 4: 52.
11. Cogswell JP, Ward J, Taylor IA, Waters M, Shi Y, Cannon B, Kelnar K, Kemppainen J, Brown D, Chen C, et al. 2008. Identification of miRNA changes in Alzheimers disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 14: 27-41.
12. Cohen JE, Lee PR, Chen S, Li W, Fields RD. 2011. MicroRNA regulation of homeostatic synaptic plasticity. Proc Natl Acad Sci 108: 11650-11655.
13. Colombo PJ, Brightwell JJ, Countryman RA. 2003. Cognitive strategy-specific increases in phosphorylated cAMP response element-binding protein and c-Fos in the hippocampus and dorsal striatum. J Neurosci 23: 3547-3554.
14. Cuellar TL, Davis TH, Nelson PT, Loeb GB, Harfe BD, Ullian E, McManus MT. 2008. Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration. Proc Natl Acad Sci 105: 5614-5619.
15. Davis TH, Cuellar TL, Koch SM, Barker AJ, Harfe BD, McManus MT, Ullian EM. 2008. Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus. J Neurosci 28: 4322-4330.
16. Dhar M, Zhu M, Impey S, Lambert TJ, Bland T, Karatsoreos IN, Nakazawa T, Appleyard SM, Wayman GA. 2014. Leptin induces hippocampal synaptogenesis via CREB-regulated microRNA-132 suppression of p250GAP. Mol Endocrinol 28: 1073-1087.
17. Durdiakova J, Warrier V, Banerjee-Basu S, Baron-Cohen S, Chakrabarti B. 2014. STX1A and Asperger syndrome: a replication study. Mol Autism 5: 14.
18. Friedman RC, Farh KK, Burge CB, Bartel DP. 2009. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19: 92-105.
19. Fujino I, Fujiwara T, Akagawa K. 1997. Transient decrease of HPC-1/syntaxin-1A mRNA in the rat hippocampus by kainic acid. Neurosci Res 28: 243-247.
20. Gao J, Wang WY, Mao YW, Graff J, Guan JS, Pan L, Mak G, Kim D, Su SC, Tsai LH. 2010a. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 466: 1105-1109.
21. Gao MC, Bellugi U, Dai L, Mills DL, Sobel EM, Lange K, Korenberg JR. 2010b. Intelligence in Williams Syndrome is related to STX1A, which encodes a component of the presynaptic SNARE complex. PLoS One 5: e10292.
22. Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S, Hammond SM, Bartel DP, Schier AF. 2005. MicroRNAs regulate brain morphogenesis in zebrafish. Science 308: 833-838.
23. Goldoni D, Yarham JM, McGahon MK, OConnor A, Guduric-Fuchs J, Edgar K, McDonald DM, Simpson DA, Collins A. 2012. A novel dual-fluorescence strategy for functionally validating microRNA targets in 3 untranslated regions: regulation of the inward rectifier potassium channel K(ir)2.1 by miR-212. Biochem J 448: 103-113.
24. Hall J, Thomas KL, Everitt BJ. 2001. Fear memory retrieval induces CREB phosphorylation and Fos expression within the amygdala. Eur J Neurosci 13: 1453-1458.
25. Hansen KF, Sakamoto K, Wayman GA, Impey S, Obrietan K. 2010. Transgenic miR-132 alters neuronal spine density and impairs novel object recognition memory. PLoS One 5: e15497.
26. Hansen KF, Karelina K, Sakamoto K, Wayman GA, Impey S, Obrietan K. 2013. miRNA-132: a dynamic regulator of cognitive capacity. Brain Struct Funct 218: 817-831.
27. Hansen KF, Sakamoto K, Pelz C, Impey S, Obrietan K. 2014. Profiling status epilepticus-induced changes in hippocampal RNA expression using high-throughput RNA sequencing. Sci Rep 4: 6930.
28. Hernandez-Rapp J, Smith PY, Filali M, Goupil C, Planel E, Magill ST, Goodman RH, Hebert SS. 2015. Memory formation and retention are affected in adult miR-132/212 knockout mice. Behav Brain Res 287: 15-26.
29. Hollander JA, Im HI, Amelio AL, Kocerha J, Bali P, Lu Q, Willoughby D, Wahlestedt C, Conkright MD, Kenny PJ. 2010. Striatal microRNA controls cocaine intake through CREB signalling. Nature 466: 197-202.
30. Huang da W, Sherman BT, Lempicki RA. 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4: 44-57.
31. Im HI, Hollander JA, Bali P, Kenny PJ. 2010. MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212. Nat Neurosci 13: 1120-1127.
32. Impey S, Smith DM, Obrietan K, Donahue R, Wade C, Storm DR. 1998. Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning. Nat Neurosci 1: 595-601.
33. Impey S, Davare M, Lesiak A, Lasiek A, Fortin D, Ando H, Varlamova O, Obrietan K, Soderling TR, Goodman RH, et al. 2010. An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling. Mol Cell Neurosci 43: 146-156.
34. Johnson R, Zuccato C, Belyaev ND, Guest DJ, Cattaneo E, Buckley NJ. 2008. A microRNA-based gene dysregulation pathway in Huntingtons disease. Neurobiol Dis 29: 438-445.
35. Kempf SJ, Casciati A, Buratovic S, Janik D, von Toerne C, Ueffing M, Neff F, Moertl S, Stenerlow B, Saran A, et al. 2014. The cognitive defects of neonatally irradiated mice are accompanied by changed synaptic plasticity, adult neurogenesis and neuroinflammation. Mol Neurodegener 9: 57.
36. Kim J, Krichevsky A, Grad Y, Hayes GD, Kosik KS, Church GM, Ruvkun G. 2004. Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci 101: 360-365.
37. Kim EJ, Leung CT, Reed RR, Johnson JE. 2007. In vivo analysis of Ascl1 defined progenitors reveals distinct developmental dynamics during adult neurogenesis and gliogenesis. J Neurosci 27: 12764-12774.
38. Kim AH, Reimers M, Maher B, Williamson V, McMichael O, McClay JL, van den Oord EJ, Riley BP, Kendler KS, Vladimirov VI. 2010. MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. Schizophr Res 124: 183-191.
39. Kim EJ, Ables JL, Dickel LK, Eisch AJ, Johnson JE. 2011. Ascl1 (Mash1) defines cells with long-term neurogenic potential in subgranular and subventricular zones in adult mouse brain. PLoS One 6: e18472.
40. Klein ME, Lioy DT, Ma L, Impey S, Mandel G, Goodman RH. 2007. Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA. Nat Neurosci 10: 1513-1514.
41. Kumarswamy R, Volkmann I, Beermann J, Napp LC, Jabs O, Bhayadia R, Melk A, Ucar A, Chowdhury K, Lorenzen JM, et al. 2014. Vascular importance of the miR-212/132 cluster. Eur Heart J 35: 3224-3231.
42. Kye MJ, Neveu P, Lee YS, Zhou M, Steen JA, Sahin M, Kosik KS, Silva AJ. 2011. NMDA mediated contextual conditioning changes miRNA expression. PLoS One 6: e24682.
43. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. 2002. Identification of tissue-specific microRNAs from mouse. Curr Biol 12: 735-739.
44. Lambert TJ, Storm DR, Sullivan JM. 2010. MicroRNA132 modulates short-term synaptic plasticity but not basal release probability in hippocampal neurons. PLoS One 5: e15182.
45. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H. 2010. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327: 198-201.
46. Lesiak A, Zhu M, Chen H, Appleyard SM, Impey S, Lein PJ, Wayman GA. 2014. The environmental neurotoxicant PCB 95 promotes synaptogenesis via ryanodine receptor-dependent miR-132 upregulation. J Neurosci 34: 717-725.
47. Li H, Mao S, Wang H, Zen K, Zhang C, Li L. 2014. MicroRNA-29a modulates axon branching by targeting doublecortin in primary neurons. Protein Cell 5: 160-169.
48. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM. 2005. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433: 769-773.
49. Lin Q, Wei W, Coelho CM, Li X, Baker-Andresen D, Dudley K, Ratnu VS, Boskovic Z, Kobor MS, Sun YE, et al. 2011. The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory. Nat Neurosci 14: 1115-1117.
50. Luhur A, Chawla G, Wu YC, Li J, Sokol NS. 2014. Drosha-independent DGCR8/Pasha pathway regulates neuronal morphogenesis. Proc Natl Acad Sci 111: 1421-1426.
51. Luikart BW, Bensen AL, Washburn EK, Perederiy JV, Su KG, Li Y, Kernie SG, Parada LF, Westbrook GL. 2011. miR-132 mediates the integration of newborn neurons into the adult dentate gyrus. PLoS One 6: e19077.
52. Lukiw WJ. 2007. Micro-RNA speciation in fetal, adult and Alzheimers disease hippocampus. Neuroreport 18: 297-300.
53. Magill ST, Cambronne XA, Luikart BW, Lioy DT, Leighton BH, Westbrook GL, Mandel G, Goodman RH. 2010. microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus. Proc Natl Acad Sci 107: 20382-20387.
54. Marler KJ, Suetterlin P, Dopplapudi A, Rubikaite A, Adnan J, Maiorano NA, Lowe AS, Thompson ID, Pathania M, Bordey A, et al. 2014. BDNF promotes axon branching of retinal ganglion cells via miRNA-132 and p250GAP. J Neurosci 34: 969-979.
55. Mayford M, Bach ME, Huang YY, Wang L, Hawkins RD, Kandel ER. 1996. Control of memory formation through regulated expression of a CaMKII transgene. Science 274: 1678-1683.
56. Mellios N, Sugihara H, Castro J, Banerjee A, Le C, Kumar A, Crawford B, Strathmann J, Tropea D, Levine SS, et al. 2011. miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity. Nat Neurosci 14: 1240-1242.
57. Miller BH, Zeier Z, Xi L, Lanz TA, Deng S, Strathmann J, Willoughby D, Kenny PJ, Elsworth JD, Lawrence MS, et al. 2012. MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function. Proc Natl Acad Sci 109: 3125-3130.
58. Mishima T, Fujiwara T, Kofuji T, Akagawa K. 2012. Impairment of catecholamine systems during induction of long-term potentiation at hippocampal CA1 synapses in HPC-1/syntaxin 1A knock-out mice. J Neurosci 32: 381-389.
59. Mitchell SJ, Ryan TA. 2005. Munc18-dependent regulation of synaptic vesicle exocytosis by syntaxin-1A in hippocampal neurons. Neuropharmacology 48: 372-380.
60. Mizuno M, Yamada K, Maekawa N, Saito K, Seishima M, Nabeshima T. 2002. CREB phosphorylation as a molecular marker of memory processing in the hippocampus for spatial learning. Behav Brain Res 133: 135-141.
61. Nakamura K, Anitha A, Yamada K, Tsujii M, Iwayama Y, Hattori E, Toyota T, Suda S, Takei N, Iwata Y, et al. 2008. Genetic and expression analyses reveal elevated expression of syntaxin 1A (STX1A) in high functioning autism. Int J Neuropsychopharmacol 11: 1073-1084.
62. Nudelman AS, DiRocco DP, Lambert TJ, Garelick MG, Le J, Nathanson NM, Storm DR. 2010. Neuronal activity rapidly induces transcription of the CREB-regulated microRNA-132, in vivo. Hippocampus 20: 492-498.
63. Nuovo GJ. 2010. In situ detection of microRNAs in paraffin embedded, formalin fixed tissues and the co-localization of their putative targets. Methods 52: 307-315.
64. Obernosterer G, Martinez J, Alenius M. 2007. Locked nucleic acid-based in situ detection of microRNAs in mouse tissue sections. Nat Protoc 2: 1508-1514.
65. Oulas A, Karathanasis N, Louloupi A, Pavlopoulos GA, Poirazi P, Kalantidis K, Iliopoulos I. 2015. Prediction of miRNA Targets. Methods Mol Biol 1269: 207-229.
66. Packer AN, Xing Y, Harper SQ, Jones L, Davidson BL. 2008. The bifunctional microRNA miR-9/miR-9 regulates REST and CoREST and is downregulated in Huntingtons disease. J Neurosci 28: 14341-14346.
67. Parras CM, Galli R, Britz O, Soares S, Galichet C, Battiste J, Johnson JE, Nakafuku M, Vescovi A, Guillemot F. 2004. Mash1 specifies neurons and oligodendrocytes in the postnatal brain. EMBO J 23: 4495-4505.
68. Porte Y, Buhot MC, Mons NE. 2008. Spatial memory in the Morris water maze and activation of cyclic AMP response element-binding (CREB) protein within the mouse hippocampus. Learn Mem 15: 885-894.
69. Remenyi J, van den Bosch MW, Palygin O, Mistry RB, McKenzie C, Macdonald A, Hutvagner G, Arthur JS, Frenguelli BG, Pankratov Y. 2013. miR-132/-212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity. PLoS One 8: e62509.
70. Ruiz-Montasell B, Aguado F, Majo G, Chapman ER, Canals JM, Marsal J, Blasi J. 1996. Differential distribution of syntaxin isoforms 1A and 1B in the rat central nervous system. Eur J Neurosci 8: 2544-2552.
71. Sanchez-Mora C, Cormand B, Ramos-Quiroga JA, Hervas A, Bosch R, Palomar G, Nogueira M, Gomez-Barros N, Richarte V, Corrales M, et al. 2013. Evaluation of common variants in 16 genes involved in the regulation of neurotransmitter release in ADHD. Eur Neuropsychopharmacol 23: 426-435.
72. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME. 2006. A brain-specific microRNA regulates dendritic spine development. Nature 439: 283-289.
73. Scott HL, Tamagnini F, Narduzzo KE, Howarth JL, Lee YB, Wong LF, Brown MW, Warburton EC, Bashir ZI, Uney JB. 2012. MicroRNA-132 regulates recognition memory and synaptic plasticity in the perirhinal cortex. Eur J Neurosci 36: 2941-2948.
74. Shaltiel G, Hanan M, Wolf Y, Barbash S, Kovalev E, Shoham S, Soreq H. 2013. Hippocampal microRNA-132 mediates stress-inducible cognitive deficits through its acetylcholinesterase target. Brain Struct Funct 218: 59-72.
75. Sheinerman KS, Tsivinsky VG, Abdullah L, Crawford F, Umansky SR. 2013. Plasma microRNA biomarkers for detection of mild cognitive impairment: biomarker validation study. Aging (Albany NY) 5: 925-938.
76. Sollner T, Bennett MK, Whiteheart SW, Scheller RH, Rothman JE. 1993a. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell 75: 409-418.
77. Sollner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE. 1993b. SNAP receptors implicated in vesicle targeting and fusion. Nature 362: 318-324.
78. Soriano P. 1999. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21: 70-71.
79. Sun G, Li H, Rossi JJ. 2010. Sequence context outside the target region influences the effectiveness of miR-223 target sites in the RhoB 3UTR. Nucleic Acids Res 38: 239-252.
80. Sunyer B, Patil S, Hoger H, Lubec G. 2007. Barnes maze, a useful task to assess spatial reference memory in the mice. Protoc Exch. doi: 10.1038/nprot.2007.390.
81. Swayne LA, Chen L, Hameed S, Barr W, Charlesworth E, Colicos MA, Zamponi GW, Braun JE. 2005. Crosstalk between huntingtin and syntaxin 1A regulates N-type calcium channels. Mol Cell Neurosci 30: 339-351.
82. Szeto CY, Lin CH, Choi SC, Yip TT, Ngan RK, Tsao GS, Li Lung M. 2014. Integrated mRNA and microRNA transcriptome sequencing characterizes sequence variants and mRNA-microRNA regulatory network in nasopharyngeal carcinoma model systems. FEBS Open Bio 4: 128-140.
83. Tognini P, Pizzorusso T. 2012. MicroRNA212/132 family: molecular transducer of neuronal function and plasticity. Int J Biochem Cell Biol 44: 6-10.
84. Tognini P, Putignano E, Coatti A, Pizzorusso T. 2011. Experience-dependent expression of miR-132 regulates ocular dominance plasticity. Nat Neurosci 14: 1237-1239.
85. Tsien JZ, Chen DF, Gerber D, Tom C, Mercer E, Anderson DJ, Mayford M, Kandel ER, Tonegawa S. 1996. Subregion and cell type-restricted gene knockout in mouse brain. Cell 87: 1327-1338.
86. van Spronsen M, van Battum EY, Kuijpers M, Vangoor VR, Rietman ML, Pothof J, Gumy LF, van Ijcken WF, Akhmanova A, Pasterkamp RJ, et al. 2013. Developmental and activity-dependent miRNA expression profiling in primary hippocampal neuron cultures. PLoS One 8: e74907.
87. Vasconcelos FF, Castro DS. 2014. Transcriptional control of vertebrate neurogenesis by the proneural factor Ascl1. Front Cell Neurosci 8: 412.
88. Viosca J, Malleret G, Bourtchouladze R, Benito E, Vronskava S, Kandel ER, Barco A. 2009. Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information. Learn Mem 16: 198-209.
89. Vo N, Klein ME, Varlamova O, Keller DM, Yamamoto T, Goodman RH, Impey S. 2005. A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc Natl Acad Sci 102: 16426-16431.
90. Wada R, Akiyama Y, Hashimoto Y, Fukamachi H, Yuasa Y. 2010. miR-212 is downregulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer. Int J Cancer 127: 1106-1114.
91. Wanet A, Tacheny A, Arnould T, Renard P. 2012. miR-212/132 expression and functions: within and beyond the neuronal compartment. Nucleic Acids Res 40: 4742-4753.
92. Wang WX, Huang Q, Hu Y, Stromberg AJ, Nelson PT. 2011. Patterns of microRNA expression in normal and early Alzheimers disease human temporal cortex: white matter versus gray matter. Acta Neuropathol 121: 193-205.
93. Wang RY, Phang RZ, Hsu PH, Wang WH, Huang HT, Liu IY. 2013. In vivo knockdown of hippocampal miR-132 expression impairs memory acquisition of trace fear conditioning. Hippocampus 23: 625-633.
94. Wayman GA, Davare M, Ando H, Fortin D, Varlamova O, Cheng HY, Marks D, Obrietan K, Soderling TR, Goodman RH, et al. 2008. An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP. Proc Natl Acad Sci 105: 9093-9098.
95. Wehner JM, Radcliffe RA. 2004. Cued and contextual fear conditioning in mice. Curr Protoc Neurosci Chapter 8: Unit 8.5C.
96. Yang JH, Qu LH. 2013. Discovery of microRNA regulatory networks by integrating multidimensional high-throughput data. Adv Exp Med Biol 774: 251-266.