Ndangariro Yomunhu Inoshanda Sei?

PKC iota/lambda, CaMKII, WWC1/KIBRA, PKMzeta

Mamorekuru anoronga sei kutsanangura imwe ndangariro kubva kune imwe? Nei zvichiita senge chero manzwiro ekupinza anotsvaga dudziro inokodzera kana mechi, pakutanga kana pakupedzisira? Chii chinoita kuti ndangariro dzive dzakangwara? Neiko kuyeuka chimwe chinhu kuchigona kuva hwaro hwengwariro—kana kuti chiito—muchimwe chinhu? Dzimwe ndangariro dzinogara sei apo dzimwe dzinopera? Pane misiyano here pakati pemamorekuru anoronga kuti ndangariro chii kubva kune anoiita kuti igare zvachose?

Pane zviviri zvinotsanangura zvinhu muuropi mune akati wandei zvidzidzo zvekurangarira, gene remorekuru uye molecule. Kana jini rikaratidzirwa—nokuda kwokuvapo kwemorekuru—ipapo ndangariro yaizoshanda, sokunge zvakadaro.

Zvino, kana imwe fungidziro yendangariro yaizogadzirwa, ingave yakafanotaurwa pajini kana kuti pamorekuru here? Zvinofungidzirwa kuti majini - senge neurons - ane mauto, nepo mamorekuru anoita. Zviri nyore, neurons uye majini aifanira kunge aripo kuti morekuru ivepo, asi ndiyo molecule inoita kuti ndangariro dzigoneke. Yakafanana neimba nezvivakwa zviri mairi zvinobatsira vanhu.

Izvi zvinoreva kuti mukuongorora hwaro hwekurangarira kwevanhu, mamorekuru ari pamberi pemajini nemaneuroni, zvine mufungo. Yese synapse, yakasimba kana isina kusimba, ine mamorekuru pamukaha. Zvinofungidzirwa kuti kuumbwa kwemamorekuru aya zvakasiyana, museti, musumbu remaneuroni, inotsanangura imwe ndangariro kubva kune inotevera. Zviri nyore, synapses inogona kutsanangurwa sekupa pulleys, asi iko kurongeka kwemamorekuru anotsanangura ndangariro.

Kune akati wandei anonzi mamorekuru endangariro, WWC1 [kana KIBRA], PKC iota/lambda [PKCι/λ], CaMKII, PKMzeta [PKMζ], cGMP/PKG, cAMP, PKA, CRE, CREB-1, CREB-2, CPEB uye zvichingodaro. Mubvunzo ndewekuongorora kuti mamorekuru anogadzirisa ndangariro uye ndeapi mamorekuru anoita kuti agare.

Zvinozivikanwa kuti kuti dzimwe ndangariro dzigare, dzokororo kazhinji inodiwa. Zvakare, mhedzisiro inogona kuve nechokwadi chekuti kuchenjerera kwenguva refu kunoshandiswa. Ipapo panogona kuva nechiitiko chakafanana, toti kumwe kukuvadzwa kana kuti chimwe chinhu chinogona kuita kuti ndangariro igare. Panogonawo kuva nekunzwisisa kwayo.

Pane pepa richangoburwa muScience , KIBRA inosimbisa chiito chePKMζ inochengetedza kuenderera kwekuyeuka , ichitaura kuti, "Mamolekemu enguva pfupi angasarudzika sei kuchengetedza kugona kweiyo activated synapses kuchengetedza ndangariro yenguva refu? Pano, tinowana itsvo uye huropi hwakaratidza adapta protein (KIBRA), postsynaptic scaffolding protein ine genetically yakabatana nehunhu hwekurangarira kuita, macomplexes ane protein kinase Mzeta (PKMζ), anchoring the kinase's potentiating action kuchengetedza nguva yekupedzisira-yenguva-refu potentiation (kunonoka-LTP) pane activated synapses. . Varwi vaviri vakasiyana veKIBRA-PKMζ dimerization inovhiringidza kunonoka-LTP uye ndangariro yenguva refu, asi hapana zvinokanganisa kutapurirana kwe-basal synaptic. ; nokudaro, vamiririri vose vanoda PKMζ nokuda kwekuita kwavo kweKIBRA-PKMζ kuchengetedza ndangariro yemwedzi-1 pasinei nekuchinja kwePKMζ chete, kana KIBRA chete, asi kuenderera mberi kwekubatana pakati pezviviri zvinochengetedza kunonoka-LTP. uye ndangariro yenguva refu. "

Kana KIBRA nePKMζ zvichifanira kudyidzana kuti zvikonzere ndangariro dzenguva refu, ndeupi humbowo hwekurangarira kwenguva refu uku kungave kuri? Kudzokorora, mhedzisiro, chiitiko chakafanana chechimwe chinhu, kana kunzwisisa kwemamiriro ezvinhu?

Hazvigoneke kuti mamorekuru echigarire chendangariro uye gadziriso yendangariro yakazvimirira zvachose nekuti chinhu chekutanga kazhinji chimiro chendangariro chisati chave chekusingaperi kana chenguva.

Somuenzaniso, motokari, magonhi, mahwindo, shangu, mabhuku, midziyo, uye zvichingodaro zvine marudzi akasiyana, uye ndangariro inodudzira zvose. Murangariro hauchengete mota dzese zvakaparadzana, asi kazhinji unounganidza zvakajairwa pakati pembiri kana kupfuura zvino wozvibatanidza mune inogona kunzi gobvu seti. Iri ndiro gobvu seti iyo inogona kuve hwaro hwechigarire hwekududzirwa kwezvakafanana ndangariro, pfungwa.

Saka mubvunzo ndewekuti makobvu seti anoshanda sei? Ipapo kumaseti matete—uko kunochengeterwa ruzivo rwakasiyana zvikuru—kunogona kuva kwechinguvana sezvo zvinhu zvakati pamsoro pesuo rimwe nerimwe zvisingayeukwi, asi izvo zvemikova zvinowanzozivikanwa nokuyeukwa.

Mamolekyulu mukugadzira anogadzirisa ndangariro, pfungwa . Kuiswa kwavo kwendangariro kunogona kusarudza kana mamorekuru echigarire angaite paari, nepfungwa. Ndiko kuvhura nekugadzira [kana kumisikidza] mamorekuru anogona kubvumira vamwe kuita, nepfungwa.

Kune zvakare basa rekudzoreredza kubva kune imwe chikamu chegobvu seti kuenda kune chinotevera, kana chimwe chikamu chendangariro kuenda kune chimwe nemagetsi masaini anogona zvakare kuona kubvumidzwa kwemamorekuru echigarire, nepfungwa. Zvinotemerwa kuti masaini emagetsi mukurova kwakaiswa pamasaini emakemikari, kuti akwane kana kuenzanisa izvo zvingave zviripo kududzirwa, pakutanga kana pakupedzisira. Mikana yekudyidzana kwekutanga neyekupedzisira imhaka yekuti masaini emagetsi akapatsanurwa, museti, neimwe ichienda mberi kwevamwe, nepfungwa.

Tsvagiridzo mumaserura uye mamorekuru neuroscience inodiwa kune neuropharmacology. Nekudaro, theoretical neuroscience inogona kutungamira nzira yekugadzira maitiro ekuisa zvidzidzo pazvinobuda kune perpendicular sarudzo dzinopesana nezvinetso zvepfungwa.

Pane bepa richangoburwa muNature , Competitive procedures shape multi-synapse plasticity pamwe chete ne dendritic segments , ichitaura kuti, "Neurons inogamuchira zviuru zvezvipo pa dendritic arbour yavo, apo ma synapses ega ega anoenda kune basa-rinoenderana nepurasitiki. neshanduko mumusoro wemuzongoza vhoriyamu. Hukuru uye kutungamira kwechimiro chepurasitiki - potentiation (sLTP) uye kuora mwoyo (sLTD) - zvinoenderana nenhamba uye kugovera kwepakati kweanosimudzira synapses uye nguva pakati pevakidzani ve synapses inoramba isina kujeka Pano isu takabatanidza nzira dzekuyedza uye dzekuenzanisira kuti tiongorore maitiro ekutanga ari pasi pe-multi-spine plasticity Takashandisa glutamate uncaging kuunza sLTP pahuwandu hwakasiyana hwemasynapses achigovera rimwe dendritic bazi. basa rehuviri Ca2 + -inotsamira chikamu chinoita kuti musana kukura kana shrinkage. Mhedzisiro yedu inoratidza kuti kukwikwidza pakati pemaspines ezviwanikwa zvemamolekyuli mutyairi akakosha we-multi-spine plasticity uye kuti nzvimbo yepakati pakati penguva imwe chete yakasimudzwa mitsipa inokanganisa mhedzisiro yemusana."

Pane rimwe bepa richangoburwa muna Nature , Mifananidzo ine zvinooneka zvakaoma-kugadzirisa zvinosiya mitsetse yakasimba yendangariro , ichitaura kuti, "Zvizhinji zvezvatinorangarira hazvisi pamusana pekusarudza nemaune, asi kungobva pakuona. Izvi zvinomutsa a Mubvunzo wekutanga nezve mavakirwo epfungwa: maonero anoita sei uye anopesvedzera ndangariro Pano, achifemerwa neyakajairwa chirevo chine chekuita nekunzwisisa kusimba kwendangariro, iyo nhanho-ye-kugadzirisa dzidziso, isu tinopa sparse coding modhi yekumisikidza maficha ekumisikidza? yemifananidzo uye kuratidza kuti zvisaririra zvekuvaka patsva kubva kune iyi modhi zvinofanotaura kuti mapikicha akaiswa sei mundangariro mune yakavhurika yekuyeuka dataset yemifananidzo yechiitiko, isu tinoratidza kuti kukanganisa kwekuvakazve hakungotsananguri kurongeka kwendangariro, asiwo kunonoka kwekupindura panguva yekudzosa, kutora, mukati. iyo yekupedzisira, iyo misiyano yese inotsanangurwa nemamodheru ane simba-chete Isu tinosimbisa kufanotaura kweakaundi iyi ne 'model-driven psychophysics'. Iri basa rinogadza kukanganisa kwekuvakazve sechiratidzo chakakosha chekubatanidza maonero uye ndangariro, pamwe kuburikidza neadaptive modulation yekunzwisisa kugadzirisa. "