REVIEW ARTICLE A synaptic model of memory:long-term potentiation in the hippocampus T.V.P.Bliss G.L.Collingridge Long-term potentiation of synaptic transmission in the ous is the primary mental model for inve asis of loa neacedyheaci9atonO the N-n ethyl e receptor endows long-term potentiation with Hebbian characteristics,and allows electrical events at the postsynaptic membrane to be transduced into chemical signals which,in turn,are thought to activate both pre-and postsynaptic mechanisms to generate a persistent increase in synaptic strength. 59 ith and burst hich sh ed n the who fibres,do not a an a pa long-tern cellula ehas been made in elucidating the mechanisms under ction and expression aircd endent synaptic potentiation occ rs within mil the This inct is now mechanistic description dependeatpoteal l the ner o hat the NMDA re performs thi by LTP w me The induction of LTP The role of amino-acid receptors in the induction of LTP.The ypes of 0 stimuli at 100 Hz r m tor channel complex reli s on seve NATURE·VOL361·7 JANUARY1993 31 1993 Nature Publishing Group
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REVIEW ARTICLE FIG.1 Basic pr 1 兴 或 100 550 的 0 3 hrs 4 Time (h) ere are o red tode a strong inp of PIP lasting 2-3 bee、 rs pr susceptibletohehwmed Because the indu g tho the allosteric glycine (for example. .the app ctivate NMDAr adoxica ling tha the Mg? which NATURE·VOL361·7 JANUARY1993 0193
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REVIEW ARTICLE d to facilita or allow the this on the activation of nMD ntago p9231 ined C for radients might be and select came than data have co Ca gin thatanmnoGergtanecg nist for mGluRs,can au this p ouehoalScdCa potentia ency ACPD es ing onbe lendriti which permeates NMDA channe re of NMDA This the postsynapti cular or t gargin 21 38 widely ass ight t ary h the induct it is bel pin e result of the acti they do so in LTPisn g Ca ar stores.Moreo at mulation elevates Ca within dendrites and spines ism.even if NMDA receptor are blocked This suggests that Ca ·35amW ate N 345 Time (s) NATURE·VOL361·7 JANUARY1S93 1993 Nature Publishing Group
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REVIEW ARTICLE tie efficiency in the hippocampus NMDA receptor-dopondent NMDA receptor-independen STP:LTP1.23 Paired-pulse tacilitatio Non-Hebbian LTP Mossy tbre LTP oute to the be due to( 1)pres s which tion such as an increas in the nun ach as reducti in uptake o he lab rele is derive nents have red the overflow of radiol the fae 10e the indu 52 or pres naptic n for least several hour that unde al ary for th Other ted purely mod has been Expression of LTF tion cted if the state NATURE·VOL361·7 JANUARY1993 0193 g Group
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BOX 2 The role of the induction of LTP ency trar 9 im ARA be induced by the agents.such as a5 eiated with as in the ane快店 changes in number,or conductance properties, AMPA hat the the expr whereas that of spite to cena But theMDA mm之nanmsion nent sion of LTP. is to monitor the late we mgntalp or more to reach ated that ca NATURE·VOL361·7 JANUARY1993 35 1993 Nature Publishing Group
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REVIEW ARTICLE AMPA● the p tAA.nmtrie L-glutamate o aptic locus" sufficient to induce ltp but is a nec facto and may be ed in he conversion sis has np nd th eral different Ca"-sen mwhichis h act ve Thishas ed to the p ha f me ence previous Dansie se to lipid-d notypic hippo mpal c hi"naectcdby ated in an NMDA cptordepSnd mbi kinas (PKA Ithas been ctiv ost-translational modificatio both esis inhibito up to 3 n of K (e) pses that have vity that m 6 vcin.which p ts the on o is acti togethe sults su t tha and a pe but fo the first hours nding LTP2 in the tior of the atal are up.or do nregulated du ationofaciP s of PKC ity has b and occlu experiments dic ation sing the pos ibility that cle wit (NCAMs),may contribute to synaptic remodelling in LTP. NATURE·VOL361·7 JANUARY1993 0193 ing Group
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REVIEW ARTICLE ests that for the first An npuoobe d fr fgghoursafncrtc ollowing the induction of LTP.(3) is dov amat and/o ch ipdPleletactvatinfactorasghs sensitivit (N)may be d AM av tO NMDA Noisdeiedioamaginneinareetioncaasc also blocks the h ry OT RNA .s.ps)in hipp But alth there has inin A ieaede nsiti labo own.na acetar further com uld ineract NO depend on th tory o he Amp ugh No component could h the r-mediat could catic o dev the a IDA An alt thes a degree that will.in part ness nge The to the p tion with presy the po cell.But ave see ntiated by ms.To nal is of induc increased and fus on of vesicles at release sites in the presynaptic NATURE·V0L361·7 JANUARY1993 1993 Nature Publishing Group
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REVIEW ARTICLE y.is it a central ed?Is LTP the ind (8)Does ental form in the do chandes in the num rs exist?f so.what are they and how do ntLTP.and to what exten ,2 here 5 m ing less than nha sting m each action ing the te s both pre-ar synapti with sin nt terminals has not nd the c er te ina ITP in ensitivity may be to single stir rolling the r dthe substa case s nt LTP in ion. nddiimgsustaine&ac ity uch as the s nthe me tally at man om the molecular to to ex age i esicles of e many ain (Ro 4. the in i the red from the dentate gyrus quence of the incre on of di phosphor ylation o 43 ch is incre ugh P.Lomo, and r NO.whic The identity of pre s R. 39 all pled to transmite 266.736-737197 Conclusion tive characteristics that define the induction criteri 2086-g011086 NATURE.VOL 361.7 JANUARY 1993 1993N ure Pub ng Group
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REVIEW ARTICLE rd 0.B.& 19 H.Neur Cole.A. Le560.346-39 USA 43-5 销 392 722-725419 ne34291892N19 P A me 度211-216192 &G W.B S 340.5 160. dberg S.H.Sveen.0.Swann.J.W Wigstrom.H.Lond 302 634 T.V.P. 245,867 70. 44.505192 e t -70001gg 7,11114161982 4 程733 sA盟.6467.647 .558-500(191. an和线13394219641 多>gan2o NATURE VOL 361-7 JANUARY 1993 9 1993 Nature Publishing Group
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