Optogenetic Inactivation Ntawm Medial Septum Impairs Long-term Object Recognition Memory Formation
Dec 04, 2023
Abstract
Theta yog ib qho ntawm cov tsiaj nyeg lub hlwb qhov tseem ceeb tshaj plaws extracellular synchronous oscillations. Hippocampaltheta tso siab rau qhov tsis zoo ntawm qhov nruab nrab septum (MS) thiab tau sau tseg tsis tu ncua thaum lub sijhawm kawm ntawm kev kawm qee yam, qhia tias nws yuav cuam tshuam rau hauv hippocampus-nyob ntawm kev ua haujlwm ntev ntev.
Kev ua haujlwm nco yog qhov tseem ceeb hauv tib neeg lub hlwb. Nws muaj cov txheej txheem xws li kev txheeb xyuas, encoding, khaws cia, thiab khaws cov ntaub ntawv. Nws yog lub peev xwm tseem ceeb hauv peb lub neej niaj hnub uas cuam tshuam nrog kev kawm, kev ua haujlwm, kev sib raug zoo, thiab lwm yam. Kev nco yog hais txog tib neeg lub hlwb lub peev xwm khaws cov ntaub ntawv, uas txiav txim siab peb lub peev xwm kawm los ntawm cov kev paub dhau los thiab siv rau hauv lub neej yav tom ntej.
Kev ua lub cim xeeb yog lub hauv paus rau kev txhim kho kev nco. Los ntawm kev ua haujlwm ntawm lub cim xeeb muaj peev xwm ua tau zoo, peb tuaj yeem nkag tau zoo dua, khaws cia, thiab khaws cov ntaub ntawv, yog li txhim kho kev nco. Thaum peb yuav tsum nco ntsoov ib daim ntaub ntawv, peb yuav tsum xub pib txheeb xyuas thiab encode cov ntaub ntawv, thiab tom qab ntawd muab cov ntaub ntawv encoded rau hauv lub hlwb lub txhab nyiaj mus sij hawm ntev. Thaum kawg, thaum peb xav siv cov ntaub ntawv no, peb tuaj yeem muab tau los ntawm kev muab rov qab. Yog tias cov txheej txheem no tau ua tiav, peb lub cim xeeb yuav zoo dua qub.
Tau kawg, lub peev xwm ua lub cim xeeb tsis tau ua tiav thaum hmo ntuj thiab yuav tsum tau txhim kho los ntawm kev cob qhia ntau ntxiv rau lub sijhawm. Piv txwv li, hais txog kev txheeb xyuas cov ntaub ntawv, peb tuaj yeem txhim kho peb qhov kev nkag siab zoo rau cov ntaub ntawv los ntawm kev tawm dag zog tas li, ua qhov kev paub ua ntej; nyob rau hauv cov nqe lus ntawm encoding thiab khaws cia cov ntaub ntawv, peb muaj peev xwm txhim kho lub cim xeeb los ntawm kev siv txoj kev xws li nco palaces; Hais txog kev khaws cov ntaub ntawv, peb tuaj yeem txhim kho qhov nrawm thiab qhov tseeb ntawm kev rov qab los ntawm kev rov ua dua.
Nyob rau hauv luv luv, nco ua thiab nco yog inseparable. Los ntawm kev cob qhia thiab kev sib txuas ntxiv ntawm cov kev paub dhau los, peb tuaj yeem txhim kho peb lub peev xwm ua lub cim xeeb, yog li txhim kho peb lub cim xeeb thiab ua rau peb lub neej muaj yeeb yuj. Nws pom tau tias peb yuav tsum txhim kho peb lub cim xeeb. Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj suav tshuaj suav nrog ntau yam tshwj xeeb, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm cov nqaij minced los ntawm ntau yam khoom xyaw uas nws muaj, nrog rau cov kua qaub, polysaccharides, flavonoids, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv ntau txoj hauv kev.
Nyem Paub Short-term Nco yuav ua li cas txhim kho
Object recognition memory (ORM) tso cai rau tsiaj los txheeb xyuas cov khoom paub thiab yog qhov tseem ceeb rau kev nco qab qhov tseeb thiab cov xwm txheej. Hauv cov nas tsuag, kev tsim ORM mus sij hawm ntev yuav tsum muaj kev ua haujlwm hippocampus tab sis kev koom tes ntawm MSin cov txheej txheem no tseem muaj teeb meem. Peb pom tias kev cob qhia cov neeg laus cov txiv neej Wistar nas nyob rau lub sijhawm ntev ORM-inducing kev kawm ua haujlwm uas cuam tshuam rau ob qhov sib txawv, tab sis kev coj tus cwj pwm sib npaug ntawm cov khoom tshiab stimuli nce hippocampaltheta lub zog, thiab qhov uas suppressing theta ntawm optogenetic MS inactivation ua rau amnesia.
Qhov tseem ceeb, qhov amnesia yog qhov tshwj xeeb rau cov khoom uas tsiaj tau tshawb nrhiav thaum MS tsis ua haujlwm. Ua ke, peb cov txiaj ntsig qhia tau hais tias MS yog qhov tsim nyog rau kev tsim ORM mus sij hawm ntev thiab qhia tias hippocampal theta kev ua si yog cuam tshuam rau cov txheej txheem no.
Ntsiab lus:
Theta atherosclerosis, Amnesia, Hippocampus, Lub hlwb oscillations, thiab kev nco mus ntev.
Cov ntawv tseem ceeb
Neural oscillations yog cov qauv rov ua dua ntawm cov kev ua haujlwm hluav taws xob uas tshwm sim spontaneously los yog teb rau stimuli. Teta yog ib qho qeeb (5-10 Hz) neuraloscillation feem ntau pom nyob rau hauv hippocampus, tshwj xeeb tshaj yog nyob rau hauv cheeb tsam CA1, qhov twg nws yog ntau li niaj zaus thiab qhia qhov siab tshaj plaws amplitude [1]. Hippocampaltheta yog rhiab heev rau medial septum (MS) lesions [2] thiab, txawm hais tias nws cov kev sib raug zoo ntawm tus cwj pwm tseem tsis tau ua tiav, cov pov thawj dav dav qhia tias nws txhawb kev kawm [3–5].
Tseeb, theta pab txhawb hippocampallong-term potentiation (LTP) [6], lub ntsiab cellular qauv ntawm hippocampus-nyob ntawm lub sij hawm ntev nco. Objectrecognition memory (ORM) tso cai rau cov tsiaj los txiav txim qhov paub txog cov khoom thiab tseem ceeb heev rau kev nco txog cov xwm txheej thiab kev npaj ua. Hauv cov nas tsuag, kev cob qhia hauv ORM-raws li kev kawm paradigm ua rau muaj ntau yam kev cuam tshuam txog kev taw qhia thiab ua rau LTP indorsal CA1, qhia tias hippocampus yog qhov tseem ceeb rau kev tsim ORM mus sij hawm ntev [7–9]. Hloov pauv, kev koom tes ntawm MS hauv cov txheej txheem no tseem muaj teeb meem. Piv txwv li, cov kab mob septal uas cuam tshuam rau qhov chaw thiab kev nco ua haujlwm tsis cuam tshuam rau lub sijhawm ntev ORM [10, 11] tab sis MS stimulation attenuates lub sij hawm ntevORM tsis txaus pom nyob rau hauv cov nas mob vwm los ntawm kev nce hippocampal theta kev ua [12].
Yog li ntawd, peb tau tsim tawm los txheeb xyuas seb MS-tswj hippocampal theta puas muaj feem cuam tshuam nrog ORM lub sijhawm ntev. Txhawm rau ua qhov no, peb cog cov khoom siv hluav taws xob hauv thaj tsam dorsal CA1 ntawm cov neeg laus txiv neejWistar nas (3 hli hnub nyoog, 300-350 g). Peb tau cob qhia lawv cov khoom tshiab-kev lees paub lub tswv yim, ua haujlwm ntevORM-inducing ua hauj lwm raws li cov nas 'natural nyiam rau novelty uas cuam tshuam rau ob qhov sib txawv tab sis coj tus cwj pwm sib npaug cov khoom tshiab A thiab Bin ib qho kev paub qhib kev sib tw rau {{10} }min (Fig. 1a) [13]. Adigital video koob yees duab tsau saum toj ntawm lub arena tau siv rau kev taug qab, kaw, thiab tshuaj xyuas cov tsiaj txoj haujlwm thiab tus cwj pwm nrog ObjectScan system software (kom paub meej saib cov ntaub ntawv ntxiv 1).
Cov xwm txheej tshawb nrhiav tau raug txhais tias Loj dua lossis sib npaug rau {{0}}}5-s-ntev lub sijhawm thaum cov tsiaj hnia thiab/los yog kov cov khoom stimuli nrog lawv cov muzzle thiab/los yog forepaws. Tag nrho lwm lub sijhawm Ntau dua lossis sib npaug ntawm 0.5 s induration tau suav tias yog cov xwm txheej kev tshawb nrhiav thiab, ntawm cov no, peb tau txiav txim siab ntxiv tsuas yog cov uas lub sijhawm txhais tau tias qhov nrawm nrawm yog tsawg dua lossis sib npaug rau qhov nruab nrab locomotionspeed ntawm txhua qhov xwm txheej tshawb nrhiav. Cov xwm txheej kav ntev< 0.5 s were excluded from the analysis. Local field potentials (LFP) were recorded continuously during the training session. Signals were amplified, digitized, filtered at cutoff frequencies of 0.3 and 250 Hz, and sampled at 1 kHz. Data from time windows corresponding to exploration and inner exploration events were extracted and analyzed often using built-in or custom-written routines (see Additional file 1 for details). As expected, the exploration time and the number of exploration events during training did not differ between objects A and B (Fig. 1b; t (5)=0.79, P=0.46 for exploration time; t (5)=1.21, P=0.28 for exploration events in paired t-test).
Kev tshawb nrhiav kev ua haujlwm tau pom thoob plaws hauv kev cob qhia (Fig. 1b).Teta kev ua si kuj tshwm sim thoob plaws hauv qhov kev sib tham no (Fig. 1c), tab sis theta lub zog, uas kwv yees kev kawm [14], tshwj xeeb tshaj yog thaum tshawb nrhiav khoom (Fig. 1d,e ). Tseeb tiag, kev tsom xam lub zog tau pom tias lub zog thetapower thaum lub sijhawm tshawb nrhiav khoom yog 36 ± 7% siab dua thaum lub sijhawm tshawb nrhiav (Fig. 1f, g; F (2, 10)=15.55; P{{12} }.0009. Obj A vs IE, P=0.002, ObjB vs IE, P=0.001 hauv Bonferroni ntau qhov kev sib piv tom qab RM one-way ANOVA).
Teta peak frequency did not differ between exploration and inter-exploration events (Fig. 1f; F (2, 10)=3.29; P=0.079 in RM one-way ANOVA). Neither the power nor the peak frequency of theta differed between object A and object B exploration epochs (Fig. 1f; Obj A vs Obj B, P>0.99 rau thetapower; Obj A vs Obj B, P=0.13 rau qhov siab tshaj zaus hauvBonferroni ntau qhov kev sib piv tom qab RM ib-txoj kev ANOVA). Ib hnub tom qab kev cob qhia, ORMretention mus sij hawm ntev tau soj ntsuam los ntawm kev rov nthuav tawm cov tsiaj rau cov khoom paub A thiab cov khoom tshiab C. Raws li xav tau, cov tsiaj nyiam tshawb nrhiav cov khoom tshiab ntawm qhov kev sim (TT; Daim duab 1h; t (5){ {9}}.95, P=0.0009 nyob rau hauv ib qho piv txwv t-test nrog theoretical mean=50).
Kev ua haujlwm MS ib txwm yog qhov tseem ceeb rau kev ua haujlwm hippocampal theta [2]. MS inactivation tau siv ua ntej los ua ib qho cuab yeej los tshem tawm hippocampal theta thaum kawm [15]. Yav dhau los, peb tau pom tias lub teeb daj (565 nm) stimulation ntawm MS ntawm nas expressing lub teeb daj-sensing optical neural silencer archaerhodopsin T (ArchT; saib Ntxiv cov ntaub ntawv 1 rau technicaldetails) [16] sai thiab reversibly tshem tawm theta hauv dorsal CA1 [17] . Yog li, txhawm rau txheeb xyuas qhov kev koom tes ntawm MS hauv kev tsim ORM mus sij hawm ntev thiab txhawm rau txheeb xyuas ntxiv seb hippocampal theta yog qhov tseeb txuas rau cov txheej txheem no, nas qhia ArchT hauv MS tau kawm hauv cov khoom tshiab-paub txog kev siv cov khoom A thiab B asstimuli, thiab daj. Lub teeb raug xa mus rau MSjust thaum lub sijhawm tshawb nrhiav (Fig. 1i).
Qhov txheej txheem no tsis cuam tshuam rau kev ua haujlwm ntawm lub tshuab nqus tsev (Daim duab 1j, k; t (39)=1.29, P=0.20 rau LigthOFF vs LightON A hauv qhov tsis sib xws t-test), lub sijhawm tshawb nrhiav khoom (Daim duab . 1l; t (39)=1.33, P=0.18 forLigthOFF vs LightON A hauv unpaired t-test), los yog tus naj npawb ntawm kev tshawb nrhiav cov xwm txheej (Fig. 1l; t (39){ {16}}.93, P=0.06for LigthOFF vs LightON A hauv unpaired t-test). Long-termORM raug soj ntsuam thaum lub sij hawm ib tug retention test session nyob rau hauv lub xub ntiag ntawm paub yam khoom A los yog paub tej khoom B nrog tshiab khoom C nqa tawm 24-h tom qab kev cob qhia. Pom tau tias tsis muaj zog ArchT-expressing tsiaj cais cov khoom A thiab B los ntawm cov khoom tshiab C (Fig. 1m,n; t (10)=5.96, P<0.0001 for test AC, t (10)=7.48, P<0.0001 for test BC in one sample t-test with theoretical mean=50); however, rats that had been delivered yellow light on the MS during object A exploration at training discriminated object B but not object A from novel object C at test (Fig. 1m, n; t (9)=1.38, P=0.19 for test AC, t (8)=7.30, P<0.0001 for test BC in one sample t-test with theoretical mean=50).
Hippocampal theta amplitude nyob ntawm locomotion ceev [18], tab sis nws tsis zoo li qhov kev hloov pauv ntawm qhov hloov pauv no tuaj yeem suav rau qhov nce hauv theta lub zog uas peb tau pom thaum lub sijhawm kev cob qhia vim tias peb tsuas yog piv cov xwm txheej tshawb nrhiav nrog cov kev tshawb fawb sib koom ua ke rau qhov sib xws. Nws kuj tseem tsis zoo li tias qhov tsis hnov tsw tshwm sim los ntawm MS inactivation yog vim kev rov qab los tsis zoo, kev kawm tsis zoo, kev tsim kho optogenetic overexpression, los yog muaj teeb meem ntawm lub teeb stimulation ib se, vim hais tias nws yog tshwj xeeb rau theobject cov tsiaj tau tshawb nrhiav thaum optogeneticsuppression tau thov, thiab lub teeb xa. tsis cuam tshuam txog kev tshawb nrhiav khoom. MS tsis yog tsuas yog ua haujlwm rau lub hippocampus xwb tab sis kuj yog lub anterior cingulate cortex (ACC) [19]. Yog li, qhov amnesia tshwm sim los ntawm MSinactivation tuaj yeem tshwm sim los ntawm kev cuam tshuam ntawm qhov kev cuam tshuam no.
Txawm li cas los xij, ACC tsis koom nrog kev tsim ORM mus sij hawm ntev [20] thiab inhibition ntawm MS-ACC qhov projections tsis cuam tshuam rau daim ntawv tshaj tawm zoo li nco [21]. Li no, nws yog qhov tsis txaus ntseeg tias kev cuam tshuam ntawm ACC kev ua haujlwm tuaj yeem suav rau peb cov txiaj ntsig uas yuav yog vim hippocampal theta inhibition. Qhov kev xav tias hippocampus yuav tsum tau ua ORM tau txais kev txhawb nqa dav dav, tab sis nws tsis tau txais kev pom zoo [22]. Piv txwv li, kev cob qhia ua ntej intra-hippocampal muscimoladministration cuam tshuam rau ORM tsuas yog thaum lub sijhawm kev cob qhia ntev dua 10 min [23], qhia tias hippocampus tsis tas yuav siv sijhawm luv luv ORMrecall, tias lwm cheeb tsam hauv lub hlwb siv lub luag haujlwm ntawm thehippocampus hauv luv- Lub sij hawm ORM kev ua haujlwm thaum nws tseem ua tsis taus rau lub sijhawm ntev, lossis lub sijhawm luv thiab ntev ORM koom nrog cov txheej txheem ywj pheej, raws li nws tau tshaj tawm rau lwm hom kev nco [24].
Hauv qhov no, peb cov ntaub ntawv qhia tias hippocampus yog qhov tseem ceeb rau kev tsim ORM mus sij hawm ntev thiab qhia ntxiv txog lub tswv yim tias ob lub sij hawm ntev ntawm cov khoom nco tau txais thaum lub sij hawm kev cob qhia hauv cov khoom tshiab paub txog kev ua haujlwm yog ywj siab [13]. Tsis tas li ntawd, qhov tseeb tias cov tsiaj txhu tau amnesic nkaus xwb rau cov khoom uas lawv tau tshawb nrhiav thaum MS tau ua haujlwm tsis zoo qhia tau tias theta tsis yog ib qho khoom ntawm kev kawm-induced neural plasticity tab sis ua haujlwm txuas nrog cov kev suav uas tshwm sim hauv hippocampus thaum lub sij hawm ntev ORM tsim.
Cov ntaub ntawv
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