Lub luag haujlwm ntawm Adult Neurogenesis hauv Hippocampal-cortical Memory Consolidation

Yog xav paub ntxiv:ali.ma@wecistanche.com

Abstract

Tau txais kev ncoyog thawj zaug nyob ntawm hippocampus (HPC) mus tas linco tsim.Qhov no hippocampal nyob ntawmnco ncozuj zus decays nrog rau lub sij hawm, ib tug txheej txheem uas yog txuam nrog ib tug maj mam nce nyob rau hauv kev vam khom rau cortical lug. Cov txheej txheem no feem ntau hu ua systems consolidation theory. Hauv daim ntawv no, peb thawj zaug tshuaj xyuas yuav ua li casncoua hippocampal-dependent rau cortical-dependent nrog rau qhov tseem ceeb ntawm kev sib cuam tshuam uas tshwm sim ntawm HPC thiab cortex thaum lub sij hawm kev sib koom ua ke. Peb kuj tseem tshuaj xyuas cov txheej txheem hauv qab ntawm qhov maj mam lwj ntawm HPC kev vam khom thaum lub sijhawm sib koom ua ke los ntawm qhov kev xav ntawmnco erasureslos ntawm cov neeg laus hippocampal neurogenesis. Thaum kawg, peb tham txog kev sib raug zoo ntawm kev sib koom ua ke thiabnco precision.

Nyem rau Cistanche DHT txhawm rau txhim kho kev nco

Ntsiab lus: Systems consolidation,Chaw taws teeb nco, Hippocampus, Synaptic plasticity, Neurogenesis

Taw qhia

Lub hippocampus (HPC) yog qhov tseem ceeb heev rau kev tsim cov kev nco qab thaum lub sijhawm mnemonic [1-5]. Hauv cov tib neeg tsis nco qab thiab cov tsiaj sim (piv txwv li, nas, nas, luav, miv, thiab liab), kev puas tsuaj rau cov qauv hippocampal feem ntau cuam tshuam rau cov kev nco tsis ntev los no, thaum yav tas los tau txais kev nco qub tseem nyob tsis tu ncua [1,6-9] . Hauv nas, Kim thiab Fanselow [8] tau tshuaj xyuas lub qhov rais ntawm lub cev thaum lub sijhawm HPC tseem ceeb rau kev nco. Txoj kev tshawb no tau ua los ntawm kev siv cov kab mob electrolytic rau HPC ntawm ntau lub sijhawm cov ntsiab lus tom qab kev ntshai ntawm cov ntsiab lus, ib qho kev kawm sib koom ua ke uas xav tau HPC thiab amygdale, nruab nrab ntawm lub chamber (cov ntsiab lus) thiab hluav taws xob footshocks uas tshwm sim hauv lub chamber [10,11 ]. Cov nas uas raug mob 1 hnub tom qab kev cob qhia tsis khaws cov ntsiab lus ntshai kev nco (1- hnub nco yog suav tias yog kev nco tsis ntev los no), hos cov tsiaj uas tau txais qhov mob 28 hnub tom qab khaws lub cim xeeb (28 hnub nco yog suav tias yog chaw taws teeb nco) . Cov txheej txheem no feem ntau hu ua systems consolidation theory [3,{12}}]. Pharmacological inactivation kev tshawb fawb siv lidocaine thiab CNQX txhaj rau hauv HPC lossis thaj chaw cortical txhawb lub tswvyim no [16-22]. Kev tshawb fawb nas Transgenic kuj txhawb lub tswv yim no. CaMKII heterozygous knockout nas pom qhov tsis txaus ntawm cortical synaptic plasticity, tab sis hippocampal synaptic plasticity yog qhov qub [23]. Cov tsiaj no tau pom tias muaj kev puas tsuaj ntawm cov chaw taws teeb retrieval, tab sis lub cim xeeb tsis ntev los no. Ib yam li ntawd, forebrain-specific dominant-negative PAK transgenic nas pom tib yam phenotypes [24].

Cov txheej txheem kev sib koom ua ke koom nrog lub sijhawm txwv kev sib cuam tshuam ntawm HPC thiab thaj chaw neocortical uas thaum kawg khaws cov cim xeeb mus ntev [22,25]. Cov kev tshawb fawb soj ntsuam kev siv cerebral qabzib [26], tam sim gene activation [16,17], thiab dendritic spine tsim [22,27] tau qhia tias ceev hauv internet encoding ntawm episodic nco nyob rau hauv HPC tuaj yeem ua raws li kev hloov pauv hauv lub cev mus ib ntus. nyob rau hauv medial prefrontal (mPFC), orbitofrontal (Orb), anterior cingulate cortex (ACC), los yog retrosplenial (RSC) cortices. Txawm li cas los xij, cov txheej txheem los ntawm kev nco tau nce zuj zus nyob ntawm cov qauv cortical thiab ywj siab ntawm HPC tseem tsis paub. Nws yog ib qho tseem ceeb tshwj xeeb los txiav txim siab txog 1) HPC thiab cortex sib txuas lus li cas kom sib sau ua ke lub cim xeeb thiab 2) yuav ua li cas HPC dependency decays nrog lub sij hawm.

Takashi Kitamura thiab Kaoru Inokuchi

Muaj ib lo lus nug tseem ceeb hais txog cov txheej txheem kev kawm ntxiv, raws li tau hais los ntawm McClelland, McNaughton, thiab O'Reilly [28]. Cov kws sau ntawv nug "vim li cas hippocampal system tsim nyog, yog tias qhov kawg kev ua tau zoo ntawm txhua hom kev ua haujlwm nco yog nyob ntawm kev hloov pauv hauv kev sib txuas hauv neocortical system? Vim li cas kev koom ua ke ntawm cov khoom tshiab rau hauv neocortical system siv sijhawm ntev li no?" Hauv kev tshuaj xyuas no, peb kuj tham txog cov kev kawm ntxiv los ntawm qhov kev xav ntawm kev nco qhov tseeb thiab kev nthuav dav.

Mechanisms ntawm cortical nco consolidation Muaj kev pom zoo ntawm ntau lub cim xeeb sib sau ua qauv sib koom ua ke ntawm HPC thiab cortex (PFC, ACC, thiab lwm yam) tom qab kev tsim lub cim xeeb tsis ntev los no yog qhov tseem ceeb rau cov txheej txheem sib sau ua ke [3,12-15 , 28] ib. Txawm li cas los xij, me ntsis paub txog qhov twg HPC Circuit Court tseem ceeb rau qhov kev sib cuam tshuam ntawm HPC thiab neocortex. Entorhinal cortex (EC) thiab HPC neuronal tes hauj lwm muaj ob qhov loj excitatory circuits, txoj kev trisynaptic (EC txheej II / dentate gyrus / CA3 / CA1 / EC txheej V) thiab txoj kev ncaj (EC txheej III / CA1 / EC txheej V) , uas converge mus rau ib hom HPC tso zis qauv, CA1 cheeb tsam [29]. CA1 cov txheej txheem tso tawm ncaj qha mus rau ntau qhov chaw cortical (PFC, ACC, RSC, Orb) lossis los ntawm EC txheej V los txuas ntawm HPC thiab ntau cov qauv cortical uas thaum kawg khaws cov cim xeeb mus ntev [30].

Kev sim thawj zaug los tshawb xyuas cov kev sib txuas no tau ua los ntawm Remondes thiab Schuman [31]. Cov kws sau ntawv no tau txiav ECIII-CA1 txoj hauv kev ncaj qha los ntawm qhov mob ntawm lub cev thiab pom tau tias qhov mob cuam tshuam rau tej thaj chaw deb nco tab sis tsis ntev los no nco hauv spatial nco ua hauj lwm thiab contextual ntshai ua hauj lwm nco. Txawm li cas los xij, tsis ntev los no, Suh et al. [32] pom tias triple transgenic nas, nyob rau hauv uas cov zis ntawm medial ECIII tau tshwj xeeb thaiv los ntawm kev qhia ntawm tetanus-toxin (TeTX) hauv medial ECIII, tsis pom muaj qhov tsis txaus hauv cov chaw taws teeb spatial nco. Yog li, kev tawm tswv yim ncaj qha los ntawm medial ECIII rau CA1 tej zaum yuav tsis yog qhov tseem ceeb rau cov txheej txheem kev sib sau ua ke.

Nakashima et al. [33] tshuaj xyuas qhov tsis sib xws no los ntawm kev ua kom zoo dua ntawm CA3-TeTX inducible transgenic nas, nyob rau hauv uas ib qho kev thaiv ntawm CA3 cov zis tau tsom tsuas yog nyob rau lub sijhawm kawm tom qab uas tau ua raws li kev ntshai ntawm cov ntsiab lus. Lawv pom tias qhov thaiv ntawm CA3 tso tawm los ntawm TeTX thaum lub sijhawm no cuam tshuam lub cim xeeb ntawm thaj chaw deb ntawm cov ntsiab lus ntshai. Cov kev tshawb fawb yav dhau los tau pom zoo tias qhov kev ua haujlwm siab ntau zaus ("ripples") hauv CA1, nrog rau kev sib koom ua ke rov ua haujlwm ntawm kev paub txog kev tua hluav taws ntawm CA1 pyramidal hlwb, tuaj yeem koom nrog hauv kev sib koom ua ke [34-40]. Nakashima et al. [33] tau qhia tias qhov zaus ntawm cov ripples thiab cov txheej txheem reactivation ob leeg tau txo qis hauv CA3-TeTX nas, txhawb qhov kev xav tias cov txheej txheem ntawm lub cev yog qhov tseem ceeb rau kev tsim cov cortical tej thaj chaw deb nco thiab yog li tseem ceeb heev rau cov txheej txheem consolidation.

Tsis ntev los no, Lesburgueres et al. [22] nrhiav kev txheeb xyuas lub sijhawm uas lub cim xeeb sib sau ua ke yog qhov tseem ceeb rau kev sib cuam tshuam ntawm HPC thiab neocortex siv cov tshuaj pharmacological tsis ua haujlwm ntev. Cov kws sau ntawv no tau tshuaj xyuas cov teebmeem ntawm kev txhaj tshuaj txhua hnub ntawm CNQX rau hauv HPC lossis Orb tom qab kev nco tau. Kev tsis ua haujlwm ntawm HPC nyob rau hnub 1-15 (thaum ntxov) tom qab kawm tau ua rau muaj qhov tsis txaus ntawm lub cim xeeb nyob deb, qhov tsis ua haujlwm nyob rau hnub 16–30 (lub sijhawm lig) tom qab kawm tsis ua rau muaj qhov tsis txaus ntawm lub cim xeeb nyob deb ({{5} } hnub nco). Qhov no qhia tau hais tias kev ua hippocampal thaum lub sijhawm ntxov yog qhov tseem ceeb rau kev tsim lub cim xeeb nyob deb. Nyob rau hauv sib piv, qhov inactivation ntawm Orb nyob rau hauv thaum ntxov los yog lig lub sij hawm ua rau ib tug tsis txaus nyob rau hauv lub tej thaj chaw deb nco. Yog li, hippocampal neuronal kev ua haujlwm yog qhov yuav tsum tau ua ntu zus (piv txwv li, thaum lub sijhawm ntxov), txawm hais tias kev ua haujlwm cortical yog ib txwm xav tau (piv txwv li, thaum lub sijhawm ntxov thiab lig). Interestingly, thaum lub Orb yog inactivated tsuas yog thaum lub sij hawm kev cob qhia, lawv pom hais tias kev puas tsuaj nyob rau hauv tej thaj chaw deb nco tsim tshwm sim yam tsis muaj tsis txaus nyob rau hauv lub 7- hnub nco [22]. Qhov no qhia tau hais tias cov kev ua haujlwm neuronal ntawm Orb thaum lub sijhawm kawm yog xav tau rau kev tsim cov chaw taws teeb nco tab sis tsis ntev los no nco, tawm tswv yim thaum ntxov los ntawm cortical tes hauj lwm rau kev sib koom ua ke ntawm kev nco mus tas li cortical nco.

Raws li cov kev tshawb fawb no, nws zoo nkaus li tias cov ntaub ntawv los ntawm cov tes hauj lwm ntawm ntau thaj chaw neocortical tau nrawm thiab txuas nrog ib ntus los ntawm HPC [22]. HPC kuj tseem ua rau cov neocortex (ACC, PFC, Orb) thaum lub sijhawm tsis ua haujlwm thiab pw tsaug zog ntawm cov nthwv dej ntse (SPWs), thaum lub sijhawm kev sib txuas ntawm thaj chaw cortical sib txawv maj mam tsim [34-40]. Ntau yam kev tshawb fawb tau pom tias lub hauv paus ntawm SPWs yog synchronous nrog cov pej xeem tawg nyob rau hauv CA3 cheeb tsam ntawm HPC [41-43] generated los ntawm nws recurrent excitatory circuit [44,45]. Reactivation los ntawm HPC ua haujlwm maj mam ntxiv dag zog rau kev sib txuas tsis muaj zog ntawm cov chaw neocortical. Thaum kawg, lub cortex tuaj yeem sawv cev rau lub cim xeeb ntawm thawj qhov xwm txheej thaum tsis muaj HPC. Yog li, qhov sib cuam tshuam zoo heev ntawm thaj av CA3 tuaj yeem pab txhawb kev sib koom ua ke ntawm kev faib cov cim xeeb uas khaws cia hauv lub cortex los ua lub cim xeeb cortical mus tas li.

Mechanisms rau kev lwj ntawm hippocampal dependency

Thaum lub sij hawm cov txheej txheem kev sib sau ua ke, lub cim xeeb ua kom muaj kev ywj pheej ntawm HPC. Qhov kev lwj ntawm hippocampal kev vam khom no yog xav tias yog ib qho txheej txheem nquag thiab ua lub luag haujlwm hauv kev tshem tawm cov kev nco qub tawm ntawm HPC thaum lub cim xeeb tau khaws cia rau hauv cov tes hauj lwm cortical, yog li tso cai rau HPC txuas ntxiv khaws cov ntaub ntawv tshiab [28]. Yog li, cov kab mob neuronal tuaj yeem tshwm sim los tshem tawm cov cim xeeb hauv HPC

HPC tau xav tias yog qhov tseem ceeb hauv kev tsim cov ntsiab lus ntawm cov ntsiab lus ntawm kev nco [30,46]. Contextual nco muaj cov koom haum ntawm cov khoom / xwm txheej thiab qhov chaw (piv txwv li, cov ntsiab lus), nrog medial EC thiab lateral EC inputs rau hauv HPC muab cov ntaub ntawv spatial thiab khoom, raws li [47]. Kev ua qauv thiab kev sim kev tshawb fawb tau pom tias lub dentate gyrus (DG) ntawm HPC muaj lub luag haujlwm tseem ceeb hauv kev ntxub ntxaug ntawm cov ntsiab lus zoo sib xws [48-52]. Tam sim ntawd kev sim noob caj noob ces tau pom tias muaj cov neeg sib txawv ntawm cov hlwb granule hauv DG tau qhib rau hauv cov ntsiab lus muab, thiab cov chaw sib txawv lossis cov haujlwm sib txawv ua kom muaj ntau haiv neeg ntawm granule hlwb [53-55]. Interestingly, tib neeg sparse ntawm granule hlwb yog qhib dua los ntawm tib ib puag ncig. Tsis ntev los no, Liu et al. [56] siv ib hom kab mob c-fos-promoter tTA transgenic nas [57,58] nrog kev xa tawm ntawm channelrhodopsin-2 (ChR2) rau hauv DG los ntawm tus kab mob adeno-txuas mus rau ncaj qha qhia tau hais tias ib txheej ntawm cov ntsiab lus. Lub cim xeeb ntsig txog DG hlwb uas yog optogenetically activated thaum lub sij hawm kawm ing lub sij hawm yog txaus kom nco qab lub ntsiab lus nco tsis muaj ib tug conditioned cue. Cov kab ntawv pov thawj no qhia tias DG encodes lub ntsiab lus nco engrams uas sawv cev rau ib puag ncig tsis sib xws.

Hauv DG, cov neurons tshiab tau tsim tawm tsis tu ncua hauv thaj tsam subgranular thoob plaws hauv cov neeg laus hauv ntau hom tsiaj, suav nrog nas, nas, liab, thiab tib neeg, txawm tias thaum laus [59-62]. Cov neurons uas tau tsim tawm tshiab tsim synapses thiab ua haujlwm ua ke rau hauv hippocampal neuronal circuits uas twb muaj lawm [63-67]. Qib ntawm cov neeg laus hippocampal neurogenesis yog qhov zoo thiab tsis zoo hloov kho los ntawm ib puag ncig, kev ua haujlwm neuronal, kev laus, thiab kev ntxhov siab [68-77]. Cov kev tshawb fawb feem ntau tau tsom mus rau lub luag haujlwm ua haujlwm ntawm neurogenesis hauv kev nco tau thiab nyob rau lub sijhawm thaum ntxov ntawm kev nco [71,78-83]. Cov kev tshawb fawb theoretical qhia tau hais tias qhov txuas txuas ntxiv ntawm cov menyuam yug tshiab neurons rau hauv cov neeg laus uas twb muaj lawm tuaj yeem cuam tshuam cov qauv ntawm cov ntaub ntawv keeb kwm yav dhau los khaws cia hauv dentate gyrus [69,84]. Feng et al. [85] generated forebrain-specific presenilin{10}} nas knock-out uas pom ib tug deficiency hauv enrichment-induced neurogenesis hauv DG. Txawm hais tias raug rau ib puag ncig zoo rau 2 lub lis piam txo qis cov lus teb khov rau hauv cov ntsiab lus ntawm kev ntshai txias hauv cov nas qus, cov nas tsuag tsis tau txo qis, qhia txog lub luag haujlwm rau cov neeg laus neurogenesis hauv hippocampal nco tshem tawm.

Kitamura et al. [19] tshuaj xyuas seb qib ntawm hippocampal neurogenesis puas cuam tshuam rau HPC-nyob ntawm lub sijhawm ntawm kev rov qab los ntawm cov ntsiab lus kev ntshai nco los ntawm kev hloov pauv tshuaj pharmacological ntawm kev ua haujlwm ntawm hippocampal neuronal (Daim duab 1). Txo cov neeg laus neurogenesis, los ntawm X-ray irradiation los yog tsub kom activin signaling [86], ua rau lub sij hawm ntev HPC-nyob ntawm cov ntsiab lus ntshai nco (Daim duab 1). Yog li, kev sib koom ua ke tsis tu ncua ntawm cov menyuam yug tshiab neurons cuam tshuam cov ntsiab lus nco hauv dentate gyrus.

Kev txo qis neurogenesis los ntawm irradiation kuj txhim kho lub sijhawm ntev ntawm kev muaj peev xwm mus ntev (LTP; [87]) ntawm nas dentate gyrus, qhia tias kev sib koom ua ke ntawm cov neurons tshiab rau hauv cov neuronal uas twb muaj lawm cuam tshuam nrog LTP persistence, uas nyob rau hauv lem yuav ua li cas rau lov tes taw LTP [19] LTP yog ib qho kev ua haujlwm ntawm neural-dependant, kev txhim kho ntev ntev hauv kev ua haujlwm ntawm synaptic, ib hom qauv ntawm synaptic plasticity [88]. LTP decay nyob rau hauv DG yog ib tug active, maj mam txheej txheem uas yog kho los ntawm N-Methyl-d-aspartic acid (NMDA) receptor; li no, kev tswj hwm txhua hnub ntawm NMDA receptor antagonist inhibits LTP lwj tom qab LTP induction [89]. Muaj kev sib raug zoo ntawm LTP thiab kev kawm thiab kev nco. Physiological, pharmacological, thiab caj ces cuam tshuam uas hloov los yog occlude LTP yog nrog los ntawm kev puas tsuaj ntawm kev kawm thiab kev nco qab [4,90]. Tsis tas li ntawd, HPC-dependent kev kawm induces LTP hauv HPC [91]. Yog li, kev kawm-induced LTP nyob rau hauv lub dentate gyrus yuav maj mam thim rov qab los ntawm cov neeg laus neurogenesis, zoo ib yam li tetanus-induced LTP. Qhov kev xav no txhais tau hais tias lub cim xeeb ntawm hippocampal tuaj yeem ploj vim muaj kev cuam tshuam los ntawm neurogenesis. Lub cev ntawm cov pov thawj no ua rau peb kwv yees tias qhov maj mam lwj ntawm HPC qhov kev cia siab ntawm kev nco tau qhia txog qhov kev tshem tawm ntawm lub hippocampal nco ib txoj kab nruab nrab los ntawm hippocampal neurogenesis.

Electron microscopic kev ntsuam xyuas kuj tau qhia tias kev sib tw synaptic ntawm cov laus thiab cov neurons tshiab tshwm sim thaum cov menyuam yug tshiab neurons tsim kev sib txuas synaptic nrog cov boutons uas twb muaj lawm hauv DG [65,66]. Tshwj xeeb tshaj yog, cov neurons tshiab tau hloov pauv hloov pauv (ntawm kwv yees li 2-6 lub lis piam ntawm lub hnub nyoog ntawm tes) tau txhim kho synaptic plasticity, qhia tias nyob rau kwv yees li 2- 6 lub lis piam ntawm hnub nyoog, cov neurons tshiab tuaj yeem muaj peev xwm ua rau tsis muaj cov synapses uas twb muaj lawm. presynaptic boutons [92,93]. Ohkawa et al. [67] kuj tau qhia tias kev koom ua ke ntawm cov menyuam yug tshiab neurons pab txhawb rau kev ua haujlwm-nyob ntawm synaptic rewiring hauv dentate gyrus. Yog li, kev koom ua ke ntawm cov neeg yug tshiab neurons cuam tshuam cov kab ke ua ntej uas twb muaj lawm hauv dentate gyrus, uas tuaj yeem ua rau lub cim xeeb tshem tawm ntawm HPC.

Raws li peb lub tswv yim, Frankland et al. [94] kuj tseem txhim kho qhov kev xav tias tsis tu ncua hippocampal neurogenesis sawv cev rau cov txheej txheem lwj uas txuas ntxiv tshem cov kev nco los ntawm hippocampus. Lawv tau thov, raws li kev cuam tshuam anterograde, cov neurogenesis txuas ntxiv tuaj yeem ua haujlwm rau kev txhawb nqa kev nco. Raws li kev cuam tshuam rov qab los, cov neurogenesis txuas ntxiv tuaj yeem ua haujlwm ntau ntxiv rau kev tau txais [94].

Kitamura et al. [19] pom tau hais tias txhim kho neurogenesis, uas tshwm sim los ntawm kev khiav lub log ce, hastens qhov lwj ntawm HPC dependence ntawm lub cim xeeb yam tsis muaj kev nco (Daim duab 1). Raws li qhov kev soj ntsuam no, kev nthuav tawm ntawm cov tsiaj mus rau ib puag ncig enrichment accelerates qhov lwj ntawm LTP hauv dentate gyrus [95] thaum tib lub sij hawm txhim kho hippocampal neurogenesis [96]. Cov txiaj ntsig no txhais tau hais tias kev rov qab los ntawm kev nco yog nyob ntawm cov khoom siv ntxiv-HPC ua yeeb yam nrog kev lwj ntawm HPC-dependency; txwv tsis pub, lub cim xeeb tsuas yuav ploj. Qhov kev txhais lus no ua rau peb kwv yees tias tej zaum yuav muaj kev sib txuas ua ke ntawm kev lwj ntawm HPC-kev vam khom thiab kev nce hauv neocortex-kev vam khom lub sijhawm.

Yuav ua li cas cov neeg laus neurogenesis pab txhawb rau kev ua kom nrawm ntawm kev hloov ntawm lub cim xeeb nyob ntawm HPC mus rau cov qauv cortical? Ib qho ua tau yog tias cov neeg laus hippocampal neurogenesis hauv DG pab tsim cov SPWs hauv CA3 [34-40]. SPWs tuaj yeem muab qhov kev ua kom tsim nyog los tsav kev sib cuam tshuam cortical plasticity thiab yog li txhawb kev sib koom ua ke ntawm cortical thaum lub sijhawm tom ntej ntawm kev tsis ua haujlwm thiab pw tsaug zog. Tsis tas li ntawd, nws tau pom tias DG tuaj yeem tswj cov noob qhia hauv ntau thaj chaw cortical thaum lub sijhawm pw tsaug zog [97] (Daim duab 2). Yog li, cov neeg laus neurogenesis hauv DG tuaj yeem muaj ob lub luag haujlwm sib txawv hauv cov txheej txheem sib sau ua ke: 1) tshem tawm cov kev nco qub hauv HPC kom muaj peev xwm khaws cia rau kev nco tshiab, thiab 2) tswj kev sib koom ua ke. Cov neeg laus neurogenesis hauv DG txo qis nrog lub hnub nyoog, uas cuam tshuam nrog kev poob qis hauv lub hnub nyoog hauv kev nco [98-100]. Muab lub peev xwm khaws cia tsis tu ncua ntawm DG, txo cov neurogenesis hauv cov tsiaj laus tuaj yeem txwv lub peev xwm ntawm HPC kom tau txais thiab khaws cov ntaub ntawv tshiab los ntawm kev txo qhov kev tshem tawm ntawm cov qub nco uas twb tau khaws cia hauv cortical tes hauj lwm. Ntawm qhov tod tes, Josselyn thiab Frankland [101] tau tawm tswv yim tias qhov nthuav dav thaum ntxov postnatal neurogenesis hauv dentate gyrus tuaj yeem piav qhia txog cov txheej txheem lom neeg ntawm infantile amnesia.

Memory age vs. Nco precision lossis generalization

Nws tau raug pom zoo tias qhov zoo ntawm cov cim tseem ceeb hloov pauv los ntawm daim ntawv meej (piv txwv li, cov ncauj lus kom ntxaws) mus rau qhov tsis tshua muaj tseeb (piv txwv li, ntau dua schematic lossis generic) daim ntawv nrog lub sijhawm kawm zoo ib yam li cov txheej txheem sib sau ua ke [{{0} }]. Sparse inter-cortical kev sib txuas tuaj yeem ua rau qee qhov tsis zoo ntawm cov ntsiab lus ntawm lub cim xeeb qub, ua rau tej thaj chaw deb nco ntau dua thiab zoo li semantic. Kev paub txog cov txheej txheem no yog qhov tseem ceeb rau kev nkag siab lub cev qhov tseem ceeb ntawm hippocampal-cortical complementary nco systems. Siv lub ntsiab lus ntawm kev ntshai kev hloov pauv, cov kev tshawb fawb [20,105] tau pom tias HPC yog ib txwm tsim nyog rau qhov tseeb ntawm qhov chaw nco, txhawb lub cim xeeb hloov lub tswv yim [103] uas qhov zoo ntawm qhov chaw nco muaj feem cuam tshuam nrog lub paj hlwb thaj tsam ntawm qhov nco ntawd. nyob ntawm. Hauv qhov sib piv, lwm txoj kev tshawb fawb [106] pom tau hais tias HPC tsis tas yuav tsum muaj kev nco meej tom qab lub sijhawm dhau los, txhawb nqa lub cim xeeb rov tsim dua tshiab [107] uas qhov zoo ntawm qhov chaw nco tsis cuam tshuam nrog thaj tsam ntawm lub hlwb. Qhov tseem ceeb, qhov sib txawv no tuaj yeem raug ntaus nqi rau qhov sib txawv ntawm cov txheej txheem sim siv rau kev koom nrog kev ntshai [108,109]. Vim tias kev koom tes nrog kev ntshai hloov pauv (piv txwv li, ntxiv dag zog lossis dav dav) qhov tseeb, peb tsis tuaj yeem txiav txim siab qhov kev ntshai tias koom nrog kev ntshai yuav npog qhov tseeb ntawm qhov chaw nco.

Txhawm rau ntsuas ncaj qha cov ntsiab lus nco tsis siv kev ntshai koom nrog kev cai, Kitamura li al. [110] tau tshuaj xyuas ib qho kev sim ib zaug thiab tsis koom nrog qhov chaw lees paub hauv cov nas thiab muab cov nas mus rau qhov chaw nyob deb ntawm qhov chaw nco (28-hnub) nrog lossis tsis muaj tshuaj tua kab mob ntawm HPC. Nyob rau hauv qhov kev ntsuam xyuas tej thaj chaw deb nco, txawm nyob rau hauv inactivation tej yam kev mob, nas pom tau hais tias adaptation mus rau ib tug tej thaj chaw deb qhov chaw tab sis tsis mus rau ib tug tshiab qhov chaw (piv txwv li, nas cais qhov chaw paub los ntawm ib tug tshiab qhov chaw), qhia tias inactivation ntawm HPC tsis inhibit. qhov precision ntawm tej thaj chaw deb ntsiab lus nco. Yog li, lub ntsiab lus nco tau raug khaws cia rau ib hlis, txawm hais tias rov qab los ntawm cov ntsiab lus nco tau hloov pauv los ntawm kev ua HPC-nyob ntawm kev ua HPC- ywj pheej nrog lub sijhawm. Qhov no qhia tau hais tias ib qho ntxiv-HPC qauv nqa cov ntaub ntawv tsis zoo rau cov ntsiab lus nco txawm tias tom qab ua ywj siab ntawm HPC yam tsis muaj kev poob ntawm cov ntsiab lus nco meej. Yog li, ib qho ntawm cov txiaj ntsig ntawm kev kawm ntxiv tuaj yeem yog kev saib xyuas qhov tseeb ntawm kev nco zoo. Qhov no yog ua raws li lub tswv yim hais tias kev sib koom ua ke sai ntawm cov ntaub ntawv tshiab uas tsis txaus ntseeg rau hauv cov qauv neocortical yuav raug zam kom tsis txhob muaj kev cuam tshuam loj heev nrog cov qauv kev paub txog cov qauv khaws cia hauv kev sib txuas synaptic ntawm neocortical neurons [25,111].

Cov lus qhia yav tom ntej

Xav txog cov txheej txheem ntawm cov txheej txheem sib sau ua ke ntawm cov ntsiab lus ntshai kev nco los ntawm qhov kev xav ntawm cov theem ntawm kev nco engram [15,56-58,112,113], ntau cov lus nug tseem ceeb tseem nyob. (1) Puas yog lub ntsiab lus nco engram hauv DG puas tau tshem tawm (lossis tsuas yog siv tsis tau) tom qab ua tiav cov kev sib koom ua ke los ntawm cov neurons tshiab? Qhov no yog ib lo lus nug tseem ceeb heev vim tias tseem muaj cov lus ceeb toom tias HPC tseem xav tau los khaws lub cim xeeb txawm tias tom qab kev sib koom ua ke (piv txwv li, cov ntsiab lus ntawm cov khoom noj nyiam nco ib txwm xav tau hippocampus) [102-105,114 ]. Goshen et al. [21] kuj hais tias optogenetic inhibitions ntawm CA1 pyramidal hlwb inhibited qhov retrieval ntawm tej thaj chaw deb contextual ntshai nco (Qhov no tsis sib xws yuav yog vim cov nyiaj them poob hauj lwm los yog cell-type-specific manipulations). (2) Yuav ua li cas lub ntsiab lus nco tau sawv cev rau hauv cov qauv cortical (hauv PFC lossis ACC) tom qab kev sib sau ua ke kom meej cov ntaub ntawv? Txhawm rau hais ncaj qha rau ob lo lus nug no, cov txheej txheem kev cog lus suav nrog kev tshaj tawm tsis ntev los no kev hloov pauv hloov pauv [115] nyob rau hauv qhov kev qhia ntawm CreER, tamoxifen-dependent recombinase, yog nyob rau hauv kev tswj hwm ntawm kev txhawb nqa kev ua haujlwm, xws li c-fos lossis kev ua haujlwm- tswj cytoskeleton-associated protein (Arc) txhawb nqa. Txoj hauv kev no tuaj yeem tso cai rau kev sau npe mus tas li ntawm cov hlwb ntsig txog lub cim xeeb hauv HPC, cortex, thiab amygdala thiab tso cai rau kev tswj hwm ntawm cov haujlwm ntawm cov hlwb no los ntsuas seb cov hlwb no tseem tseem ceeb rau kev rov qab los ntawm cov chaw taws teeb nco.

Txawm hais tias kev siv tshuaj kho mob thiab kev kho mob txuas ntxiv tseem muaj txiaj ntsig zoo rau kev sim kev nco txog ntawm HPC thiab thaj chaw cortical, txoj hauv kev siv cov nas transgenic ua ke nrog cov thev naus laus zis, uas kev tswj hwm ntawm tes ntawm tes yog txwv ntau rau cov pej xeem ntawm kev nco txog. cov hlwb, tso cai rau kev txhim kho lub cev- thiab kev nco engram-raws li kev txheeb xyuas thiab yog qhov zoo dua rau kev nkag siab txog cov txheej txheem ntawm cov txheej txheem sib sau ua ke.

Kev siv

1. Scoville WB, Milner B: Kev nco tsis ntev los no tom qab ob tog hippocampal lesions. J Neurol Neurosurg Psychiatry 1957, 20:11–21.

2. O'Keefe J, Nadel L: Hippocampus raws li daim ntawv qhia kev paub. Oxford: Clarendon Xovxwm; Xyoo 1978.

3. Eichenbaum H: Lub cortical-hippocampal system rau kev tshaj tawm nco. Nat Rev Neurosci 2000, 1:41–50.

4. Morris RG, Moser EI, Riedel G, Martin SJ, Sandin J, Hnub M, O'Carroll C: Cov ntsiab lus ntawm cov kev xav ntawm neurobiological ntawm lub hippocampus: lub luag hauj lwm ntawm kev ua si-dependent synaptic plasticity hauv kev nco. Philos Trans R Soc Lond B Biol Sci 2003, 358:773–786.

5. Neves G, Cooke SF, Bliss TV: Synaptic plasticity, memory, and the hippocampus: a neural network approach to causality. Nat Rev Neurosci 2008, 9:65–75.

6. Zola-Morgan SM, Squire LR: Lub primate hippocampal tsim: pov thawj rau lub luag haujlwm txwv lub sijhawm hauv nco. Science 1990, 250:288–290.

7. Squire LR: Nco thiab hippocampus: ib qho kev sib txuas los ntawm kev tshawb pom nrog nas, liab, thiab tib neeg. Psychol Rev 1992, 99:195–231.

8. Kim JJ, Fanselow MS: modality-specific retrograde amnesia of ntshai. Science 1992, 256:675–677.

9. Squire LR, Stark CE, Clark RE: Qhov nruab nrab ntawm lub ntsej muag lobe. Annu Rev Neurosci 2004, 27:279–306.

10. Phillips RG, LeDoux JE: Kev sib txawv ntawm amygdala thiab hippocampus rau cued thiab contextual ntshai txias txias. Behav Neurosci 1992, 106:274–285.

11. Kim JJ, Rison RA, Fanselow MS: Cov teebmeem ntawm amygdala, hippocampus, thiab periaqueductal grey lesions ntawm luv- thiab ntev-ntev kev ntshai. Behav Neurosci 1993, 107:1093–1098.

12. Willshaw DJ, Buckingham JT: Kev ntsuam xyuas ntawm Marr txoj kev xav ntawm lub hippocampus ua lub cim xeeb ib ntus. Philos Trans R Soc Lond B Biol Sci 1990, 329:205–215.

13. Wiltgen BJ, Brown RA, Talton LE, Silva AJ: Tshiab circuits rau qub nco: lub luag hauj lwm ntawm neocortex nyob rau hauv consolidation. Neuron 2004, 44:101–108.

14. Frankland PW, Bontempi B: Lub koom haum ntawm kev nco tsis ntev los no thiab tej thaj chaw deb. Nat Rev Neurosci 2005, 6:119–130.

15. Dudai Y: Qhov chaw nyob tsis tswm: kev sib koom ua ke yeej tsis kawg. Annu Rev Neurosci 2012, 35:227–247.

16. Frankland PW, Bontempi B, Talton LE, Kaczmarek L, Silva AJ: Kev koom tes ntawm anterior cingulate cortex nyob rau hauv tej thaj chaw deb contextual ntshai nco. Science 2004, 304:881–883.

17. Maviel T, Durkin TP, Menzaghi F, Bontempi B: Qhov chaw ntawm neocortical reorganization tseem ceeb rau tej thaj chaw deb nco. Science 2004, 305:96–99.

18. Frankland PW, Teixeira CM, Wang SH: Kev muab qhab nia gradient: Cov pov thawj rau lub sij hawm-dependent nco reorganization nyob rau hauv cov tsiaj sim. Debates Neurosci 2007, 1:67–78.

19. Kitamura T, Saitoh Y, Takashima N, Murayama A, Niibori Y, Agata H, Sekiguchi M, Sugiyama H, Inokuchi K: Cov neeg laus neurogenesis modulates lub hippocampus-nyob ntawm lub sij hawm ntawm associative ntshai nco. Cell 2009, 139:814–827.

20. Wiltgen BJ, Zhou M, Cai Y, Balaji J, Karlsson MG, Parivash SN, Li W, Silva AJ: Lub hippocampus plays lub luag hauj lwm xaiv nyob rau hauv lub retrieval ntawm cov ncauj lus kom ntxaws contextual nco. Curr Biol 2010, 20:1336–1344.

21. Goshen I, Brodsky M, Prakash R, Wallace J, Gradinaru V, Ramakrishnan C, Deisseroth K: Dynamics ntawm retrieval tswv yim rau tej thaj chaw deb nco. Cell 2011, 147:678–689.

22. Lesburgueres E, Gobbo OL, Alaux-Cantin S, Hambucken A, Trifilieff P, Bontempi B: Thaum ntxov tagging ntawm cortical tes hauj lwm yog yuav tsum tau rau kev tsim ntawm enduring associative nco. Science 2011, 331:924–928.

23. Frankland PW, O'Brien C, Ohno M, Kirkwood A, Silva AJ: Alpha-CaMKII dependent plasticity nyob rau hauv lub cortex yog yuav tsum tau rau kev nco mus tas li. Xwm Txheej 2001, 411:309–313.

24. Hayashi ML, Choi SY, Rao BS, Jung HY, Lee HK, Zhang D, Chattarji S, Kirkwood A, Tonegawa S: Hloov kho cortical synaptic morphology thiab impaired memory consolidation in forebrain- particular dominant-negative PAK transgenic nas. Neuron 2004, 42:773–787.

25. Lisman J, Morris RG: Memory. Vim li cas lub cortex yog tus kawm qeeb? Xwm Txheej 2001, 411:248–249.

26. Bontempi B, Laurent-Demir C, Destrade C, Jaffard R: Lub sij hawm-dependent reorganization ntawm lub hlwb circuitry nyob rau hauv lub sij hawm ntev nco cia. Xwm Txheej 1999, 400:671–675.

27. Restivo L, Vetere G, Bontempi B, Ammassari-Teule M: ​​Kev tsim ntawm kev nco tsis ntev los no thiab tej thaj chaw deb yog txuam nrog lub sij hawm-dependant tsim ntawm dendritic spines nyob rau hauv lub hippocampus thiab anterior cingulate cortex. J Neurosci 2009, 29:8206–8214.

28. McClelland JL, McNaughton BL, O'Reilly RC: Vim li cas thiaj muaj kev kawm ntxiv hauv hippocampus thiab neocortex: kev nkag siab los ntawm kev ua tiav thiab tsis ua tiav ntawm cov qauv kev sib txuas ntawm kev kawm thiab kev nco. Psychol Rev 1995, 102:419–457.

29. Amaral DG, Witter MP: Lub koom haum peb-dimensional ntawm hippocampal tsim: kev tshuaj xyuas cov ntaub ntawv anatomical. Neuroscience 1989, 31:571–591.

30. Andersen P, Morris R, Amaral D, Bliss T, O'Keefe J (Eds): Phau Ntawv Hippocampus. New York: Oxford University Press; Xyoo 2007.

31. Cov Lus Ceeb Toom M, Schuman EM: Lub luag haujlwm rau kev nkag mus rau cortical rau hippocampal cheeb tsam CA1 hauv kev sib sau ua ke ntawm kev nco mus ntev. Xwm Txheej 2004, 431:699–703.

32. Suh J, Rivest AJ, Nakashima T, Tominaga T, Tonegawa S: Entorhinal cortex txheej III input rau lub hippocampus yog ib qho tseem ceeb rau lub sij hawm lub koom haum nco. Science 2011, 334:1415–1420.

33. Nakashima T, Buhl DL, McHugh TJ, Tonegawa S: Hippocampal CA3 tso zis tseem ceeb heev rau ripple-associated reactivation thiab consolidation ntawm nco. Neuron 2009, 62:781–787.

34. Buzsaki G: Ob-theem qauv ntawm lub cim xeeb kab tsim: ib lub luag hauj lwm rau lub hlwb hais tias "tsis nrov". Neuroscience 1989, 31:551–570.

35. Wilson MA, McNaughton BL: Reactivation of hippocampal ensemble memories thaum pw tsaug zog. Science 1994, 265:676–679.

36. Buzsaki G: Kev sib tham hippocampal-neocortical. Cereb Cortex 1996, 6:81–92.

37. Chiapas AG, Wilson MA: Kev sib koom tes ntawm hippocampal ripples thiab cortical spindles thaum pw tsaug zog qeeb. Neuron 1998, 21:1123–1128.

38. Skaggs WE, McNaughton BL: Replay ntawm neuronal firing sequences nyob rau hauv nas hippocampus thaum pw tsaug zog tom qab spatial kev. Science 1996, 271:1870–1873.

39. Lee AK, Wilson MA: Nco txog kev ua ntu zus hauv hippocampus thaum pw tsaug zog qeeb. Neuron 2002, 36:1183–1194.

40. Ji D, Wilson MA: Coordinated nco replay nyob rau hauv lub qhov muag cortex thiab hippocampus thaum pw tsaug zog. Nat Neurosci 2007, 10:100–107.

41. Ylinen A, Bragin A, Nadasdy Z, Jando G, Szabo I, Sik A, Buzsaki G: Nthuav yoj-txuas nrog high-frequency oscillation (200 Hz) nyob rau hauv qhov tsis zoo hippocampus: network thiab intracellular mechanisms. J Neurosci 1995, 15:30–46.

42. Csicsvari J, Hirase H, Mamiya A, Buzsaki G: Sib sau ua ke cov qauv ntawm hippocampal CA3-CA1 neurons thaum lub sij hawm muaj kev cuam tshuam nrog cov pej xeem. Neuron 2000, 28:585–594.

43. Maier N, Nimmrich V, Draguhn A: Cellular and network mechanisms underlying spontaneous sharp wave-ripple complexes in mouse hippocampal slices. J Physiol 2003, 550:873–887.

44. Miles R, Wong RK: Inhibitory tswj ntawm lub zos excitatory circuits nyob rau hauv lub guinea-pig hippocampus. J Physiol 1987, 388:611–629.

45. Traub RD, Miles R, Wong RK: Tus qauv ntawm lub hauv paus chiv keeb ntawm cov neeg nyob hauv lub hippocampal hlais. Science 1989, 243:1319–1325.

46. ​​Guzowski JF, McNaughton BL, Barnes CA, Worley PF: Environment-specific expression of the instant-early gene Arc in hippocampal neuronal ensembles. Nat Neurosci 1999, 2:1120–1124.

47. Hargreaves EL, Rao G, Lee I, Knierim JJ: Loj dissociation ntawm medial thiab lateral entorhinal input rau dorsal hippocampus. Science 2005, 308:1792–1794.

48. Marr D: Simple memory: ib txoj kev xav rau archicortex. Philos Trans R Soc Lond B Biol Sci 1971, 262:23–81.

49. Treves A, Rolls ET: Kev txheeb xyuas ntawm lub luag haujlwm ntawm hippocampus hauv kev nco. Hippocampus 1994, 4:374–391.

50. Leutgeb S, Leutgeb JK, Barnes CA, Moser EI, McNaughton BL, Moser MB: Independent codes for spatial and episodic memory in hippocampal neuronal ensembles. Science 2005, 309:619–623.

51. McHugh TJ, Jones MW, Quinn JJ, Balthasar N, Coppari R, Elmquist JK, Lowell BB, Fanselow MS, Wilson MA, Tonegawa S: Dentate gyrus NMDA receptors mediate sai sai qauv sib cais nyob rau hauv lub hippocampal network. Science 2007, 317:94–99.

52. Nakashima T, Cushman JD, Pelkey ​​KA, Renaudineau S, Buhl DL, McHugh TJ, Rodriguez Barrera V, Chittajallu R, Iwamoto KS, McBain CJ, Fanselow MS, Tonegawa S: Young dentate granule cells mediate pattern granule, whereas cov hlwb pab txhawb kev ua tiav cov qauv. Cell 2012, 149:188–201.

53. Chawla MK, Guzowski JF, Ramirez-Amaya V, Lipa P, Hoffman KL, Marriott LK, Worley PF, McNaughton BL, Barnes CA: Sparse, environmentally selective expression of Arc RNA in the upper blade of the nas fascia dentata by luv luv kev paub spatial. Hippocampus 2005, 15:579–586.

54. Satvat E, Schmidt B, Argraves M, Marrone DF, Markus EJ: Cov kev hloov hauv kev xav tau hloov cov qauv ntawm zif268 qhia hauv cov hniav gyrus. J Neurosci 2011, 31:7163–7167.

55. Schmidt B, Marrone DF, Markus EJ: Disambiguating the similar: the dentate gyrus and pattern separation. Behav Brain Res 2012, 226:56–65.

56. Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K, Tonegawa S: Optogenetic stimulation ntawm hippocampal engram activates ntshai nco nco. Xwm Txheej 2012, 484:381–385.

57. Reijmers LG, Perkins BL, Matsuo N, Mayford M: Localization ntawm ib tug ruaj khov neural correlate ntawm associative nco. Science 2007, 317:1230–1233.

58. Matsuo N, Reijmers L, Mayford M: Spine-type-specific recruitment of newly synthesized AMPA receptors with learning. Science 2008, 319:1104–1107.

59. Altman J, Das GD: Autoradiographic thiab histological pov thawj ntawm postnatal hippocampal neurogenesis hauv nas. J Comp Neurol 1965, 124:319–335.

60. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH: Neurogenesis nyob rau hauv cov neeg laus hippocampus. Nat Med 1998, 4:1313–1317.

61. Gould E, Reeves AJ, Fallah M, Tanapat P, Gross CG, Fuchs E: Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci USA 1999, 96:5263–5267.

62. Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, Boström E, Westerlund I, Vial C, Buchholz BA, Possnert G, Mash DC, Druid H, Frisén J: Dynamics ntawm hippocampal neurogenesis hauv cov neeg laus tib neeg. Cell 2013, 153:1219–1227.

63. van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH: Functional neurogenesis nyob rau hauv cov neeg laus hippocampus. Xwm Txheej 2002, 415:1030–1034.

64. Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH: Distinct morphological theem ntawm dentate granule neuron maturation nyob rau hauv cov laus nas hippocampus. J Neurosci 2006, 26:3–11.

65. Toni N, Teng EM, Bushong EA, Aimone JB, Zhao C, Consiglio A, van Praag H, Martone ME, Ellisman MH, Gage FH: Synapse formation on neurons yug hauv cov neeg laus hippocampus. Nat Neurosci 2007, 10:727–734.

66. Toni N, Laplagne DA, Zhao C, Lombardi G, Ribak CE, Gage FH, Schinder AF: Neurons yug hauv cov neeg laus dentate gyrus tsim cov synapses nrog lub hom phiaj. Nat Neurosci 2008, 11:901–907.

67. Ohkawa N, Saitoh Y, Tokunaga E, Nihonmatsu I, Ozawa F, Murayama A, Shibata F, Kitamura T, Inokuchi K: Tus txha caj qaum tsim qauv ntawm cov neeg laus yug los neurons yog qhov sib txawv ntawm lub sijhawm induction thiab qhov chaw ntawm hippocampal plasticity. PLoS One 2012, 7:e45270.

68. Ming GL, Nkauj H: Cov neeg laus neurogenesis nyob rau hauv cov tsiaj hauv nruab nrab lub paj hlwb. Annu Rev Neurosci 2005, 28:223–250.

69. Lledo PM, Alonso M, Grubb MS: Adult neurogenesis thiab functional plasticity in neuronal circuits. Nat Rev Neurosci 2006, 7:179–193.

70. Tashiro A, Sandler VM, Toni N, Zhao C, Gage FH: NMDA-receptor-mediated, cell-specific integration of new neurons in the adult dentate gyrus. Xwm Txheej 2006, 442:929–933.

71. Zhao C, Deng W, Gage FH: Mechanisms thiab functional implications of adult neurogenesis. Cell 2008, 132:645–660.

72. Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H: Neuronal activated-induced Gadd45b txhawb nqa epigenetic DNA demethylation thiab neeg laus neurogenesis. Science 2009, 323:1074–1077.

73. Kitamura T, Mishina M, Sugiyama H: Txhim kho neurogenesis los ntawm kev khiav lub log ce yog suppressed nyob rau hauv nas tsis muaj NMDA receptor epsilon 1 subunit. Neurosci Res 2003, 47:55–63.

74. Kitamura T, Mishina M, Sugiyama H: Kev txwv kev noj zaub mov nce hippocampal neurogenesis los ntawm molecular mechanisms ywj siab ntawm NMDA receptors. Neurosci Lett 2006, 393:94–96.

75. Kitamura T, Sugiyama H: Khiav lub log qoj ib ce ua kom lub cev muaj zog hauv cov nas dentate gyrus. Neurosci Res 2006, 56:45–52.

76. Kitamura T, Saitoh Y, Murayama A, Sugiyama H, Inokuchi K: LTP induction nyob rau hauv ib lub sij hawm nqaim tseem ceeb ntawm cov theem tsis paub tab txhim kho txoj sia nyob ntawm cov neurons tshiab tsim nyob rau hauv cov neeg laus nas dentate gyrus. Plaub Hlis 2010, 3:13.

77. Inokuchi K: Cov neeg laus neurogenesis thiab kev hloov kho ntawm neural circuit muaj nuj nqi. Curr Opin Neurobiol 2011, 21:360–364.

78. Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E: Neurogenesis nyob rau hauv cov neeg laus yog koom tes nyob rau hauv lub tsim ntawm kab cim. Xwm Txheej 2001, 410:372–376.

79. Winocur G, Wojtowicz JM, Sekeres M, Snyder JS, Wang S: Inhibition ntawm neurogenesis cuam tshuam nrog hippocampus-dependent nco muaj nuj nqi. Hippocampus 2006, 16:296–304.

80. Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, Monckton JE, Garcia AD, Sofroniew MV, Kandel ER, Santarelli L, Hen R, Drew MR: Ablation of hippocampal neurogenesis impairs contextual ntshai conditioning thiab synaptic plasticity hauv lub dentate gyrus. Proc Natl Acad Sci USA 2006, 103:17501–17506.

81. Zhang CL, Zou Y, He W, Gage FH, Evans RM: Lub luag haujlwm rau cov neeg laus TLX-positive neural qia hlwb hauv kev kawm thiab kev coj cwj pwm. Xwm Txheej 2008, 451:1004–1007.

82. Dupret D, Revest JM, Koehl M, Rochas F, De Giorgi F, Costet P, Abrous DN, Piazza PV: Spatial relational memory yuav tsum hippocampal neeg laus neurogenesis. PLoS IB 2008, 3:e1959.

83. Imayoshi I, Sakamoto M, Ohtsuka T, Takao K, Miyakawa T, Yamaguchi M, Mori K, Ikeda T, Itohara S, Kageyama R: Lub luag hauj lwm ntawm nruam neurogenesis nyob rau hauv lub structural thiab kev ua haujlwm siab ntawm cov neeg laus forebrain. Nat Neurosci 2008, 11:1153–1161.

84. Meltzer LA, Yabaluri R, Deisseroth K: Lub luag hauj lwm rau circuit homeostasis hauv cov neeg laus neurogenesis. Trends Neurosci 2005, 28:653–660.

85. Feng R, Rampon C, Tang YP, Shrom D, Jin J, Kiin M, Sopher B, Miller MW, Ware CB, Martin GM, Kim SH, Langdon RB, Sisodia SS, Tsien JZ: Deficient neurogenesis in forebrain-specific presenilin-1 nas knockout yog txuam nrog txo kev tshem tawm ntawm hippocampal nco kab. Neuron 2001, 32:911–926.

86. Agata H, Murayama A, Migishima R, Kida S, Tsuchida K, Yokoyama M, Inokuchi K: Activin nyob rau hauv lub hlwb modulates kev txhawj xeeb txog tus cwj pwm thiab cov neeg laus neurogenesis. PLoS IB 2008, 3:e1869.

87. Bliss TV, Lomo T: Ntev-ntev potentiation ntawm synaptic kis tau tus mob nyob rau hauv lub dentate cheeb tsam ntawm lub anesthetized luav tom qab stimulation ntawm txoj kev perforant. J Physiol 1973, 232:331–356.

88. Bliss TV, Collingridge GL: Ib tug qauv synaptic ntawm kev nco: lub sij hawm ntev potentiation nyob rau hauv lub hippocampus. Xwm Txheej 1993, 361:31–39.

89. Villarreal DM, Do V, Haddad E, Derrick BE: NMDA receptor antagonists txhawb nqa LTP thiab spatial nco: cov txheej txheem nquag kho LTP lwj. Nat Neurosci 2002, 5:48–52.

90. Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC: Cia cov ntaub ntawv spatial los ntawm kev saib xyuas mechanism ntawm LTP. Science 2006, 313:1141–1144.

91. Whitlock JR, Heynen AJ, Shuler MG, Bear MF: Kev kawm ua rau lub sijhawm ntev zog hauv hippocampus. Science 2006, 313:1093–1097.

92. Schmidt-Hieber C, Jonas P, Bischofberger J: Enhanced synaptic plasticity nyob rau hauv tshiab generated granule hlwb ntawm cov neeg laus hippocampus. Xwm Txheej 2004, 429:184–187.

93. Ge S, Yang CH, Hsu KS, Ming GL, Song H: Lub sijhawm tseem ceeb rau kev txhim kho synaptic plasticity hauv cov neurons tshiab ntawm cov neeg laus lub hlwb. Neuron 2007, 54:559–566.

94. Frankland PW, Kohler S, Josselyn SA: Hippocampal neurogenesis thiab tsis nco qab. Trends Neurosci 2013, 36:497–503.

95. Abraham WC, Logan B, Greenwood JM, Dragunow M: Induction and experience-dependent consolidation of stability long-term potentiation last month in the hippocampus. J Neurosci 2002, 22:9626–9634.

96. Kempermann G, Kuhn HG, Gage FH: Ntau hippocampal neurons nyob rau hauv cov laus nas nyob rau hauv ib tug enriched ib puag ncig. Xwm Txheej 1997, 386:493–495.

97. Ribeiro S, Mello CV, Velho T, Gardner TJ, Jarvis ED, Pavlides C: Induction of hippocampal long-term potentiation while waking leads to increase extrahippocampal zif-268 expression while ensuing quick-eye-movement sleep. J Neurosci 2002, 22:10914–10923.

98. Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV, Abrous DN: Spatial nco ua yeeb yam ntawm cov laus nas nyob rau hauv dej maze kwv yees theem ntawm hippocampal neurogenesis. Proc Natl Acad Sci USA 2003, 100:14385–14390.

99. Drapeau E, Montaron MF, Aguerre S, Abrous DN: Kev kawm-vim txoj sia nyob ntawm cov neurons tshiab nyob ntawm qhov kev paub ntawm cov nas muaj hnub nyoog. J Neurosci 2007, 27:6037–6044.

100. Lazarov O, Mattson MP, Peterson DA, Pimplikar SW, van Praag H: Thaum neurogenesis ntsib kev laus thiab kab mob. Trends Neurosci 2010, 33:569–579.

101. Josselyn SA, Frankland PW: Infantile amnesia: a neurogenic hypothesis. Kawm Mem 2013, 19:423–433.

102. Nadel L, Moscovitch M: Memory consolidation, retrograde amnesia, thiab hippocampal complex. Curr Opin Neurobiol 1997, 7:217–227.

103. Moscovitch M, Nadel L, Winocur G, Gilboa A, Rosenbaum RS: Kev paub txog neuroscience ntawm tej thaj chaw deb episodic, semantic thiab spatial nco. Curr Opin Neurobiol 2006, 16:179–190.

104. McKenzie S, Eichenbaum H: Consolidation thiab reconsolidation: ob lub neej ntawm kev nco? Neuron 2011, 71:224–233.

105. Winocur G, Moscovitch M, Sekeres M: Memory consolidation or transformation: context manipulation and hippocampal sawv cev ntawm kev nco. Nat Neurosci 2007, 10:555–557.

106. Wang SH, Teixeira CM, Wheeler AL, Frankland PW: Qhov tseeb ntawm tej thaj chaw deb cov ntsiab lus nco tsis xav tau lub hippocampus. Nat Neurosci 2009, 12:253–255.

107. Squire LR, Bayley PJ: Lub neuroscience ntawm tej thaj chaw deb nco. Curr Opin Neurobiol 2007, 17:185–196.

108. Houston FP, Stevenson GD, McNaughton BL, Barnes CA: Qhov cuam tshuam ntawm lub hnub nyoog ntawm kev nthuav dav thiab incubation ntawm kev nco hauv F344 nas. Kawm Mem 1999, 6:111–119.

109. Balogh SA, Radcliffe RA, Logue SF, Wehner JM: Contextual and cued fear conditioning in C57BL/6 J and DBA/2 J nas: context discrimination and the effects of retention interval. Behav Neurosci 2002, 116:947–957.

110. Kitamura T, Okubo-Suzuki R, Takashima N, Murayama A, Hino T, Nishizono H, Kida S, Inokuchi K: Hippocampal muaj nuj nqi yog tsis tas yuav tsum tau rau qhov precision ntawm tej thaj chaw deb chaw nco. Plaub Hlis 2012, 5:5.

111. McClelland JL: Koom nrog kev kawm ceev neocortical ntawm New schema cov ntaub ntawv zoo ib yam rau hauv kev kawm ntxiv kev kawm txoj kev xav. J Exp Psychol Gen 2013, 142:1190–1210.

112. Han JH, Kushner SA, Yiu AP, Cole CJ, Matynia A, Brown RA, Neve RL, Guzowski JF, Silva AJ, Josselyn SA: Neuronal kev sib tw thiab kev xaiv thaum lub cim xeeb tsim. Science 2007, 316:457–460.

113. Han JH, Yiu AP, Cole CJ, Hsiang HL, Neve RL, Josselyn SA: Nce CREB nyob rau hauv lub auditory thalamus txhim khu kev nco thiab generalization ntawm auditory conditioned ntshai. Kawm Mem 2008, 15:443–453.

114. Sutherland RJ, Lehmann H: Lwm txoj kev xav ntawm kev nco sib koom ua ke thiab lub luag haujlwm ntawm hippocampus ntawm cov kab ke hauv cov nas. Curr Opin Neurobiol 2011, 21:446–451.

115. Guenthner CJ, Miyamichi K, Yang HH, Heller HC, Luo L: Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations. Neuron 2013, 78:773–784.