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Pls nyem qhov no mus rau Part 1

Pls nyem qhov no mus rau Ntu 3

Cistanche tuaj yeem txhim kho kev nco

Raws li cov kev tshawb pom no, peb yuav tshuaj xyuas tom ntej yog tias muaj kev tswj hwm hippocampal miR-466f-3p qhia hauv nas raws li kev kawm spatial thiabncotsim kuj cuam tshuam neuronal morphology hauv vivo. Qhov tseem ceeb, peb pom tias qhov nruab nrab ntawm tus txha nraub qaum ntawm hippocampal neurons ntawm GLN nas yog siab dua li ntawm PLN nas, raws li qhia los ntawm Golgi impregnation ntawm lub pyramidal.

Daim duab 3. Cov teebmeem ntawm kev hloov pauv ntawm hippocampal miR-466f-3p qhia theem ntawm nas MWM kev ua tau zoo

(A) Kev sim ncua sij hawm ntawm MWM txoj haujlwm, kev tshuaj ntsuam xyuas, lossis kev ntsuas electrophysiology ntawm nas hlwb tom qab txhaj tshuaj lentivirus.

(B) Sab laug panels: qhia txog dsRed hauv nas hippocampus. Tus neeg sawv cev qis- thiab siab- magnification IF cov duab ntawm hippocampus los ntawm nas kis nrog lentiviruses recombinant ex- nias dsRed-tsuas yog kev tswj hwm (sab laug ntawm cov duab) lossis miR-466f-3p ntxiv rau dsRed (txoj cai kem ntawm cov duab). Lub thawv ntim ntawm ob daim duab saum toj kawg nkaus tau nthuav dav thiab pom hauv qab no. Scale bar, 100 mm. Cov kab dotted qhia txog thaj tsam ntawm DG. Nuclei tau stained nrog DAPI. GCL, granule cell txheej; ML, molecular txheej. Txoj cai histogram, txheeb ze qhia theem ntawm miR-466f-3p hauv nas hippocampus kis tus kab mob lentivirus qhia txog kev tswj lossis miR-466f-3p, raws li kev soj ntsuam los ntawm RT-qPCR ( n=16 ib pab).

(C) MWM kev ua yeeb yam ntawm cov nas kis nrog cov kab mob sib txawv recombinant lentiviruses, ntim nrog kev siv tsib yam plasmids qhia dsRed-tsuas yog, miR-466f-3p, mut-miR-466f{ {5}}p, thiab miR/SCR-sponges, ntsig txog, rau hauv lawv lub hippocampus (n=13, 26, 16, 19, thiab 11 ib pab pawg, raws li). Sab laug vaj huam sib luag: khiav latency thaum lub sij hawm kev cob qhia. Txoj cai vaj huam sib luag: tus neeg khiav tawm latency ntawm 6th ntu.

Cov ntaub ntawv qhia hauv (B) tau nthuav tawm raws li txhais tau tias ± SD, thiab cov ntaub ntawv qhia hauv (C) tau nthuav tawm raws li qhov txhais tau tias ± SEM. Kev txheeb xyuas qhov tseem ceeb tau raug ntsuas los ntawm qhov tsis sib xws t test (B), ob txoj kev ANOVA nrog Bonfer- roni post hoc piv (C, sab laug vaj huam sib luag), lossis ib-ANOVA nrog Tukey's post hoc test (C, sab xis vaj huam sib luag). Cov lej sib txawv: #p < 0.05,="" **/##p="">< 0.01="" thiab="" ****p="">< 0.0001;="" *mir-466f{10}}p="" piv="" rau="" lwm="" tus;="" #mir-sponge="" tiv="" thaiv="" kev="" tswj="">

neurons hauv GLN thiab PLN nas hippocampus (Daim duab S3). Cov kev tshawb pom no qhia tau hais tias kev txhim kho ntawm hippocampal miR-466f-3p txhawb nqa neurite outgrowth thiab dendritic txha nraub qaum, uas zoo ib yam li induction ntawm txha nraub qaum pom nyob rau hauv hippocampus ntawm GLN nas txheeb ze rau PLN nas.

miR-466f-3p zoo modulates nas spatial kev kawm thiabncokev ua tau zoo, nrog rau synaptic plasticity

Txhawm rau tshawb xyuas seb miR-466f-3p puas tswj tau tus nas spatial kawm thiabncotsim, peb siv ib tug recombinant lentivirus kab mob mus kom ze rau overexpress lub miRNA nyob rau hauv nas hippocampus. Cov nas tau txheeb xyuas 7 hnub tom qab txhaj tshuaj lentivirus rau hauv DG (Daim duab 3A). Cov duab sawv cev ntawm cov hip-expression theem ntawm miR-466f-3p tau nce siab tiag tiag hauv miR-466f-3p pawg overexpression piv rau pawg tswj hwm (txoj cai histogram hauv daim duab 3B). Peb pom tias nas nrog hippocampal overexpression ntawm miR-466f- 3p thiab raug rau MWM txoj haujlwm tau nthuav tawm kev khiav tawm latencies ntawm 88 ± 5 s hauv 1st kev sib kho thiab 19 ± 1 s hauv 6th ntu (liab dot kab, Daim duab 3C), uas zoo dua rau vector tswj nas (dub kab) lossis mutant tswj nas (kab liab kab) thiab zoo ib yam li cov khiav tawm latencies ntawm GLN nas tau piav qhia hauv daim duab 1A. Nyob rau tib lub sijhawm, peb tau tshuaj xyuas qhov cuam tshuam ntawm miR-466f-3p tsis ua haujlwm ntawm kev kawm spatial thiabncolos ntawm inhibiting miR-466f-3p siv miR-sponge. Tshwj xeeb tshaj yog, MWM kev ua tau zoo ntawm cov nas uas hippocampal miR-466f-3p raug kaw los ntawm miR-sponge zoo ib yam li cov nas PLN, piv txwv li, lawv tsis tau kawm nrhiav lub platform txawm tias los ntawm qhov kev sib kho zaum kawg (khoom ntsuab square kab,

Daim duab 3C). Tsis tas li ntawd, cov nas txhaj tshuaj lentivirus tsis tau tshwm sim los cuam tshuam cov yas hauv tsev, vim qee cov nas hauv txhua pab pawg tau kawm lossis tsawg kawg yog nyob rau hauv cov txheej txheem ntawm kev kawm thaum lub sijhawm kawg (Daim duab 3C, txoj cai histogram).

Muab hais tias overexpression ntawm miR-466f-3p hauv nas hippocampus txhim kho lawv txoj kev kawm thiabncomuaj peev xwm, peb txheeb xyuas qhov sib piv electrophysiology ntawm kab lis kev cai hippocampal neurons qhia ntau theem ntawm miR-466f-3p. Cov me me excitatory postsynaptic tam sim no (mEPSC) los ntawm DIV14 hippocampal neurons overexpressing miR-466f-3p los yog mut-miR-466f-3p, miR-sponge, los yog tswj tau kaw siv tag nrho-cell thaj clamps. Thaum tsis muaj qhov sib txawv tseem ceeb hauv mEPSC amplitude, nce Tau, lossis lwj Tau ntawm plaub pawg qauv, mEPSC zaus ntawm cov neurons tshaj tawm miR-466f-3p tau ntau dua piv rau Lwm pab pawg (Daim duab 4A), qhia tias postsynaptic glutaminergic receptors tau ua kom muaj zog ntau dua ntawm miR-466f- 3p overexpression.

Peb mam li ntsuas lub sijhawm ntev (LTP) los txiav txim ncaj qha lub luag haujlwm ntawm miR-466f-3p hauv synaptic plasticity hauv vivo. Weinjectedthehippocampusofmicewithrecombinantlentivirus asdescribedFigure3andtheninducedLTPinhippocampalslices los ntawm tetanic stimulation (peb lub tsheb ciav hlau ntawm high-frequency stimulation [3xHFS]) ntawm Schaffer collateral pathway. Peb pom tias peb cov txheej txheem txhawb nqa LTP hauv txhua pab pawg, raws li pom los ntawm kev pheej hmoo nce ntxiv hauv thaj chaw excitatory postsynaptic muaj peev xwm (fEPSPs) hauv cheeb tsam cornu ammonis 1 (CA1) (Daim duab 4B, sab laug vaj huam sib luag). Lub LTP muaj zog dua hauv miR-466f-3p-overexpressing slices (188 feem pua ​​± 2 feem pua ​​​​ntawm cov hauv paus ntawm 40-50 min tom qab stimulation, txhais tau tias ± SEM) piv rau mutant (169 feem pua ​​± 1 feem pua ntawm lub hauv paus), SCR- daim txhuam cev (173 feem pua ​​​​± 3 feem pua ​​​​ntawm cov hauv paus), thiab tswj cov kab mob kis kab mob (159 feem pua ​​± 2 feem pua ​​​​ntawm cov hauv paus), raws li miR-466f-3p inhibition los ntawm miR-sponge txo LTP (128 feem pua ​​​​± 1 feem pua ​​​​ntawm cov hauv paus) txheeb ze rau kev tswj hwm (Daim duab 4B, txoj cai vaj huam sib luag). Peb kuj ntsuas LTP ntawm pawg GLN thiab PLN tom qab kev cob qhia. Cov ntaub ntawv ntsig txog kuj tau qhia qhov sib txawv tseem ceeb hauv fEPSP txoj kab nqes hauv thaj tsam CA1 ntawm pawg GLN thiab PLN (Daim duab 4C). Yog li, qib siab ntawm miR-466f-3p txhim kho LTP thiab synaptic plasticity uas, dhau los, tuaj yeem txhawb kev kawm thiabncomuaj peev xwm ntawm nas. Ua ke, cov ntaub ntawv nthuav tawm hauv daim duab 2, 3, thiab 4 qhia tau tias miR-466f-3p ua lub luag haujlwm tseem ceeb hauv kev kawm spatial thiabncotsim, zoo li los ntawm kev txhim kho tus txha caj qaum, LTP, thiab lub zog ntawm synaptic plasticity.

Mef2a mRNA yog lub hom phiaj tswj hwm ntawm miR-466f-3p

Peb tau tshawb xyuas bioinformatics los txheeb xyuas cov hom phiaj mRNAs tswj los ntawm kev khi ntawm miR-466f-3p rau lawv 30 UTRs. Ntawm cov neeg sib tw peb tau txheeb xyuas yog Mef2a mRNA encoding MEF2A. Interestingly, MEF2A kev qhia yav dhau los tau pom tias yuav raug txo qis tom qab kev cob qhia MWM, thiab overexpression ntawm qhov teeb meem no ua rau muaj kev cuam tshuam tsis zoo rau kev ua yeeb yam ntawm nas (Cole et al., 2012). Yog li ntawd, peb siv lub luciferase reporter assay los tshuaj xyuas yog miR-466f-3p tswj kev txhais lus ntawm Mef2a mRNA los ntawm kev khi rau nws 30 UTR. Peb tau ntxig cov tsiaj qus los yog mutant Mef2a 30 UTR ib ntus nqes ntawm ib qho SV40-promoter-driven luciferase cDNA (Luc), ua rau tus neeg sau xov xwm plasmid psiCHECK2-MEF2A 30 UTR lossis psiCHECK2- mut-MEF2A 30 UTR (Daim duab 5A). Raws li pom nyob rau hauv sab laug histogram ntawm daim duab 5B, co-expression ntawm miR-466f-3p attenuated qhov kev qhia ntawm luciferase qhia los ntawm Mef2a 30 UTR. Cov txiaj ntsig no tau tshwm sim los ntawm kev sib cuam tshuam ntawm miR-466f-3p thiab Mef2a 30 UTR txij li kev hloov pauv ntawm qhov kwv yees qhov chaw sib txuas ntawm miR-466f-3p rau lub Mef2a 30 UTR (50-UGU- GUAU-30) los yog thaj av noob ntawm miR-466f-3p (50-AUACACA-30) Kev lees paub Mef2a 30 UTR tshem tawm cov nyhuv inhibitory ntawm miR-466f-3p ntawm kev ua luciferase (Daim duab 5B, nruab nrab histogram). Tsis tas li ntawd, kev sib koom ua ke ntawm miR-sponge, tab sis tsis yog CR daim txhuam cev, kuj tshem tawm cov kev cuam tshuam ntawm miR-466f-3p ntawm kev ua luciferase (Daim duab 5B, txoj cai histogram). Qhov tseem ceeb, tsis muaj kev tshaj tawm ntawm miR-466f-3p lossis miR-sponge tau muaj kev cuam tshuam rau qib ntawm Mef2a mRNA hauv thawj hippocampal neurons (Daim duab 5C), tab sis lawv tau txo lossis nce, feem, qib MEF2A protein (Daim duab 5D). Peb kuj pom tau hais tias overexpression ntawm miR-466f-3p los yog miR-sponge, feem, downregulated los yog upregulated lub mRNA theem ntawm kev ua-regulated cytoskeletal txuam protein (Arc) nyob rau hauv thawj hippocampal neurons (Daim duab 5C) , uas yog lub hom phiaj nqes hav uas paub zoo tswj los ntawm MEF2A (Flavell li al., 2006)

Peb kuj tau ua cov fluorescence nyob rau hauv situ hybridization (FISH) los ntes miR-466f-3p thiab ua ke nrog IF labeling ntawm MEF2A hauv DIV14 thawj hippocampal neurons tsis muaj lossis nrog kev kho mob forskolin. Forskolin paub tias induce chemical LTP thiab qhib adenylyl cyclase, yog li nce intracellular cAMP qib. Peb pom nuclear colocalization ntawm MEF2A nrog miR-466f- 3p, raws li tau piav qhia los ntawm cov duab sawv cev hauv daim duab 5E. Tom qab forskolin stimulation, txawm li cas los xij, miR-466f-3p teeb liab tau nce hauv ob qho tib si soma thiab dendrites, whereas MEF2A teeb liab hauv

nucleus poob qis, raws li qhia los ntawm kev hloov pauv ntawm kev siv ntawm MEF2A thiab Fast Red signals, ntsig txog, ntawm tus kheej cov hlwb neuronal (Daim duab 5E). Nyob rau hauv tas li ntawd, cov ntaub ntawv nyob rau hauv daim duab 5A–5E qhia tau hais tias miR-466f-3p tsis zoo tswj kev qhia ntawm MEF2A protein los ntawm kev khi rau 30 UTR ntawm Mef2a mRNA thiab yog li txwv tsis pub nws txhais lus.

Raws li cov txiaj ntsig tau piav qhia saum toj no, peb pom tias qib hippocampal ntawm MEF2A cov protein tau txo qis hauv GLN nas tom qab kev cob qhia MWM, tab sis tsis yog hauv PLN nas (Daim duab 5F). Tsis tas li ntawd, cov txheeb ze ntawm MEF2A nyob rau hauv ib tus neeg GLN nas (dots) thiab PLN nas (squares) inversely correlated nrog cov theem ntawm miR-466f-3p (R=0.60, Daim duab 5G). Yog li, heterogeneous qauv ntawm spatial kawm thiabncoKev muaj peev xwm raug hloov kho los ntawm stochastic nce ntawm hippocampal miR- 466f-3p hauv ib tus nas thiab qhov ua rau txo qis ntawm MEF2A raws li kev txhawb nqa ntawm kev ua haujlwm neuronal.

Stochastic activation ntawm hippocampal CREB thiab qhov kev hloov pauv hloov pauv ntawm miR- 466-669 pawg thaum MWM kev cob qhia

WeinvestigatedthemechanismsbywhichmiR-466f-3p hauv nas hippocampus tuaj yeem raug tswj hwm los ntawm MWM txoj haujlwm. Muaj peb lub miRNA precursors encoding miR-466f-3p, tag nrho cov uas muaj nyob rau hauv cov nas tshwj xeeb miR-466-669 pawg nyob rau hauv intron 10 ntawm nws tus tswv gene, mSfmbt2 (Inoue li al. ., 2017) (Daim duab 6A). Interestingly, nyob rau hauv sib piv rau miR-466f-3p, tsis muaj qhov sib txawv tseem ceeb nyob rau hauv cov lus qhia theem ntawm mSfmbt2 nruab nrab ntawm cov GLNandPLNgroups (Daim duab 6B), qhia tias cov miR-466-669 pawg yuav encode ib daim ntawv sau tseg. es tsis txhob ua ib feem ntawm cov ntaub ntawv tseem ceeb ntawm mSfmbt2. Raws li, peb tau tsim ntau pawg ntawm primers los txheeb xyuas cov ntaub ntawv tseem ceeb ntawm miR-466-669 pawg los ntawm RT-qPCR. Raws li tau piav qhia hauv daim duab 6A, ib qho PCR ntev (ntxiv rau 282 txog 2,381), ua ke nrog cov kab sib tshooj qPCR, xws li A (ntxiv rau 282 txog 115), B (131 txog 406), C (388 txog 686), D (662 txog 1,028), E (1,004 txog 1,299), F (1,242 txog 1,629), G (1,605 txog 2,029), thiab H (2,005 txog 2,381), tuaj yeem kuaj pom hauv nas hippocampus, tab sis tsis yog ntu 376 txog 2 ( ) (cov ntaub ntawv tsis qhia). Cov ntaub ntawv no txhawb nqa tias miR-466-669 pawg encoded ib daim ntawv ntev ntev nyob ze ze li ntawm 2,388 bp upstream ntawm thawj miRNA precursor (ie, pre-mir-466m, cim ntxiv rau 1inFigure6A). Zoo kawg nkaus, zoo ib yam li qhov peb pom rau miR-466f-3p, qhov nruab nrab ntawm cov ntawv sau no hauv hippocampus ntawm GLN nas yog siab dua rau PLN nas (Daim duab 6C). Yog li, txhim kho kev kawm thiabncomuaj peev xwm ntawm GLN nas yog vim transcriptional activation ntawm miR-466-669 pawg.

Kev ua kom muaj nuclear CREB los ntawm phosphorylation thaum lub sij hawm MWM cov dej num lossis lwm yam kev kawm yog ib kauj ruam tseem ceeb rau kev hloov lub sij hawm luv mus rau lub sij hawm ntev.nco(Lisman et al., 2018; Roger-son et al., 2014). Yog li, peb tau tshawb xyuas yog tias qhov sib txawv ntawm miR-466f-3p ntawm ib tus nas uas ua haujlwm MWM tuaj yeem cuam tshuam nrog cov xwm txheej ua haujlwm ntawm CREB. Txhawm rau tshawb xyuas lub tswv yim no, ua ntej peb tshuaj xyuas cov qib phosphorylation ntawm hippocampal CREB hauv ib tus nas. Raws li pom hauv daim duab 6D, CREB ua kom (los ntawm phosphorylation ntawm residue S-133) tau txhim kho hauv GLN nas txheeb ze rau PLN thiab HC nas. Peb kuj tau lees paub tias miR-466f-3p tau raug qhia nrog pCREB hauv cov neurons los ntawm kev ua miRNA ISH ua ke nrog IF staining ntawm pCREB thiab MAP2 hauv thawj hippocampal neurons (Daim duab S2A). Tsis tas li ntawd, cov ntaub ntawv tseem ceeb ntawm miR- 466-669 pawg tau sib raug zoo nrog pCREB hauv GLN nas (R=0.52), qhov tsis zoo nrog pCREB hauv PLN nas (R=0) .71) (Daim duab 6E). Peb tau txheeb xyuas qhov sib txheeb ntawm cov theem ntawm lwm yam tseem ceeb, phos-pho-extracellular signal-regulated kinase (pERK), thiab cov ntawv sau thawj theem ntawm miR-466-669 pawg. Peb pom tias ob hom MWM-kev cob qhia nas tau nthuav tawm qhov kev sib raug zoo ntawm miR-466-669 pawg teeb liab thiab pERK (R=0.59 thiab 0.48, raws li; Daim duab S4A), thiab tsis muaj qhov txawv ntawm pERK/ tERK qhia ntawm ob pawg (Daim duab S4B). Txhawm rau kom paub meej ntxiv txog qhov cuam tshuam ntawm CREB ua rau ntawm kev hloov pauv ntawm cov txheej txheem ntawm cov txheej txheem ntawm R-466-669clusterand, yog li ntawd,

inductionofmiR-466f-3p,weusedaspecificCREBinhibitor,666- 15 (Xie li al., 2015), ua ke nrog forskolin kev kho mob ntawm DIV14 thawj hippocampal neurons. Forskolin paub tias yuav qhib CREB phosphorylation (Malhotra li al., 2015). Peb pom tias pretreatment ntawm thawj hippocampal neurons nrog 666-15 thaiv forskolin-induced CREB activation (Daim duab 6F) thiab txo cov theem ntawm miR-466f-3p thiab miR-466-669 pawg Cov ntawv sau tseg (Daim duab 6G thiab 6H). Concomitantly, mRNA qib ntawm cov pCREB lub hom phiaj paub cov noob nurr1 thiab homer1a (Bridi li al., 2017; Jensen li al., 2017) kuj raug txo los ntawm 666-15 kev kho mob (Daim duab 6H). Muab ua ke, Daim duab 6 qhia tau hais tias stochastic activation ntawm CREB nyob rau hauv lub hippocampus ntawm ib tug subpopulation ntawm inbred nas nyob rau hauv MWM ua hauj lwm induces transcription ntawm lub miR-466-669 pawg thiab, yog li ntawd, induction ntawm miR-466f{23 }}p, yog li txhim kho lawv cov kev kawm spatial thiabncomuaj peev xwm ua tau zoo dua hauv txoj haujlwm.

Kev sib tham

Peb tau tshawb nrhiav lub luag haujlwm ua tau ntawm miRNAs hauv kev hloov kho qhov sib txawv ntawm kev kawm spatial thiabncontawm inbred C57BL/6J nas. Peb qhia tias kev ua kom stochastic ntawm CREB thiab qhov kev tswj hwm ntawm hippocampal miR-466f-3p suav rau kev kawm ntau dua thiabncomuaj peev xwm ntawm ib pawg ntawm peb cov nas xeem, tej zaum yuav yog vim miR-466f-3p mediating translational inhibition ntawm Mef2a mRNA uas encodes covncoTsis zoo regulator MEF2A. Peb qhov kev tshawb pom muab qhov xwm txheej uas qhia txog kev ua haujlwm thiab hloov pauv lub luag haujlwm ntawm ib qho tshwj xeeb miRNA hauv kev tswj kev paub los ntawm stochastic induction ntawm CREB-pCREB-miR-466f-3p-MEF2A axis los ntawm ib puag ncig stimuli.

Txoj haujlwm MWM tau siv dav los tshuaj xyuas qhov sib txawv ntawm qhov kev kawm spatial thiabncorau nas. Nyob rau hauv ib txwm muaj xwm txheej, nas siv cov cues distal los taw qhia lawv tus kheej, cia lawv kawm thiab nco txog qhov chaw ntawm lub platform zais hauv txoj haujlwm. Feem ntau ntawm peb qhov kev sim inbred C57BL/6J nas (62 feem pua) tau nthuav tawm ib qho qauv ntawm kev khiav tawm latency, nrhiav lub platform nyob rau hauv 30 s los ntawm ntu 3rd-6th (Daim duab 1A, GLN). Hauv qhov sib piv, ib pawg nas (38 feem pua) tsis tau kawm txoj haujlwm txawm tias los ntawm 6th ntu (PLN). Qhov tseem ceeb, peb kuj tau raug cov nas mus rau ob qhov kev xeem paub. Thawj yog qhov kev kuaj pom tshiab (NOR), uas yog ib qho kev sim ib zaug raws li kev tshawb nrhiav hauv lub cev yam tsis muaj kev txhawb zog lossis kev ntxhov siab los txhawb tus cwj pwm (Leger li al., 2013). Kev sib raug zoo ntawm NOR thiab MWM cov dej num hais txog kev ua yeeb yam nas tsis zoo (R {{1{{20}}}}}.13), uas zoo ib yam li kev sib raug zoo ntawm NOR kev ua yeeb yam thiab qib hippocampal qhia ntawm miR-466f-3p (R=0.01; cov ntaub ntawv tsis qhia). Qhov kev ntsuam xyuas NOR kuj tau qhia tias tsis muaj qhov sib txawv ntawm qhov kev ntxub ntxaug ntawm pawg MWM GLN thiab PLN (0.36 ± 0.25 piv rau 0.29 ± 0.18; Daim duab S1B). Lwm yam kev kawm spatial thiabnco-Txoj haujlwm peb tau thov yog Barnes maze (BM), uas zoo ib yam li MWM. Nws yog raws li qhov kev xav tias cov nas tsuag muab tso rau hauv qhov chaw tsis zoo yuav tsum kawm thiab nco ntsoov qhov chaw ntawm lub thawv khiav tawm nyob hauv qab ntawm lub platform. Raws li pom nyob rau hauv daim duab S1C, peb tau pom tias cov nas ua yeeb yam hauv BM sojntsuam sim kuj muaj kev cuam tshuam zoo nrog rau qib hippocampal qhia ntawm miR-466f-3p. Yog li, induction ntawm CREB-pCREB-miR-466f-3p-MEF2A axis hauv hippocampus thaum kawm thiabncotsim yog spatial ntsiab lus-nyob ntawm seb.