Ubuso obunzima bokucindezeleka - izifundo ezimbili zivala izimpawu emagundeni, kodwa ngezindlela ezihlukile
Elebhu eStanford University, igundane libonisa izimpawu zokucindezeleka. Emasontweni ama-10 azungezile, uye wabhekana nochungechunge lokucasuka, kusukela emanzini angenakho ukudla noma amanzi, kumaphethini okulala okungaqondakali. Manje, isisusa saso siphansi-lapho sithathwa umsila, kwenza imizamo embalwa yokubalekela, futhi azama ukuhlola izikhala ezintsha. Kanti futhi kancane ukuthanda ukusiphuza kusuka liquid ishukela - isibonakaliso ukuthi uthola injabulo encane emisebenzini evamile evamile. Akulula neze ukuhlola impilo yengqondo yesilwane, kodwa leli gundane libonisa ngokucacile ezinye izimpawu zakudala zokucindezeleka.
Kodwa hhayi isikhathi eside.
Ngaphambili, Kay Tye futhi Julie Mirzabekov yashintsha igundane ukuze i-flash of light ingenza kusebenze ingxenye encane yobuchopho bayo-the indawo ye-ventral tegmental (VTA), eduze kobuchopho obuseduze futhi eseduze ne-midline. Ukukhanya okugqamile, nokuziphatha kwegundane kushintsha cishe ngaso leso sikhathi. Ihlushwa uma iqhutshwa phezulu, ihlola izindawo ezivulekile, futhi ibuyisela izinyo layo elimnandi. Ukukhanya okugqamile, futhi izimpawu zayo ziphela.
Kodwa ngaphesheya kwezwe, eNtabeni iSinayi School of Medicine, UDipesh Chaudhury noJessica Walsh benza into efanayo nomphumela ohluke ngokuphelele. Izitshalo zabo ziye zashintshwa ngendlela efanayo, ukuze ukukhanya kungashintsha ne-VTA neurons yabo. Kodwa lezi zinduku ziye zabhekana nohlobo olufushane kodwa olunamandla kakhulu lokucindezeleka-izinsuku ezingu-10 zokufakwa emaceleni ngamabangi amakhulu, abanobudlova. Ngenxa yokuhlaselwa okulandelayo, ezinye zazo ziye zaveza izimpawu zokucindezeleka. Abanye banamandla kakhulu. Kodwa lapho uChaudhury noWalsh bashaya i-VTAs lezi amagundane, abantu abanamandla abaguqulwa baba yizinkinga.
Zombili izifundo zasebenzisa izindlela ezifanayo zokwenza i-neurons engxenyeni efanayo yobuchopho ... futhi yaba nemiphumela ehluke ngokuphelele. Ekulweni kukaTye no-Mirzabekov, amagundane acindezelekile aqala ukuziphatha kwawo okujwayelekile. Esifundweni sikaChaudhury noWalsh, amagundane aphephile akhonjiswa Okuningi izimpawu ezicindezelekile.
Imizila eminingi eya ekucindezelekeni
Womabili amaqembu acabanga ukuthi imiphumela ephikisanayo ephikisana nayo ingenxa yezinhlobo ezahlukene zokucindezeleka ezitholwa yizinduku. Izilwane ze-tye zathola ukucindezeleka okungapheli, njengamandla omuntu lapho ebhekana nokungavikeleki emsebenzini njalo. I-Chaudury kanye namagundane kaWalsh babhekene nokucindezeleka okukhulu "kokuhlukunyezwa kwezenhlalakahle" ngesikhathi esifushane, okufana nomuntu othole umlenze. Lokhu okuhlangenwe nakho okungafani nakho kungathinta izingxenye ezifanayo zobuchopho, kodwa benza ngezindlela ezahlukene. "Wonke umuntu unomlando wakhe wokuphila, futhi uhlangabezana nokucindezeleka noma ukuhlukunyezwa okuhlukile," kusho uMing-Hu Han, owahola isifundo sesibili. "Kungenzeka ukuthi uma uqhathanisa izimpawu kubantu ababili abanokucindezeleka, bahluke."
Le miphumela igcizelela isimo esinzima sokucindezeleka. Kunemibangela eminingi engabangela ukuthi ingasebenza ebuchosheni ngezindlela ezihlukile, ngisho noma ingathonya indawo efanayo, futhi ikhiqize izinkanyezi ezifanayo.
Lokhu kungabuye kuchaze ukuthi kungani kungekho ukulingana komuntu oyedwa-wonke ukwelashwa kokucindezeleka. "Ngisho nemithi ephumelela kakhulu isebenzela i-subset, kanti ezinye izindlela zokwelashwa zisebenza kahle ngeziguli ezithile kodwa zenza kube nzima nakakhulu kwabanye," kusho uTye, manje ophethe ilabhu yakhe eMasachussetts Institute for Technology. Ucwaningo olwenziwe ngama-anti-depressants luye ... kahle ... ukucindezeleka okuncane. Naphezu komlando wamashumi ayishumi nanhlanu, kuncane kakhulu okuthuthukisiwe okwenziwayo kule minyaka eyishumi edlule. "Kule minyaka engamashumi amahlanu edlule, akukho ukuthuthukiswa okuqhubekayo okwenziwayo," kusho Gal Yadid kusuka eBar-Ilan University e-Israel.
Kodwa lezi zifundo ezintsha, nakuba zenziwe ezinkambeni, zinikeza izinkomba eziningi ezingabangela ukwelashwa okusha. Baphendula izingxenye zobuchopho ezibandakanyeka ezimpawu, zibonisa ukuthi lezo zimpawu zingakwazi ukuguqulwa ngokushesha kakhulu, futhi zisitshela kabanzi ngamakhemikhali ahilelekile.
Iningi lamanje lamanje lamanzi e-anti-depressants, njenge-Prozac, landa amazinga ebuchopho be-chemical serotonin, ngenxa yokuthi amazinga aphansi aholela ekucindezelekeni. Kodwa le mbono ayikwazi ukuhamba kahle. Okokuqala, le mithi ayisebenzi kuwo wonke umuntu. Futhi uma benza, bangathatha izinyanga ukuze badle. Uma izidakamizwa zisebenza ngoba zikhulise amazinga e-serotonin, kufanele asebenze amahora angakapheli. Njengoba kunjalo, kubonakala sengathi benza ngokungaqondile.
Singenza kangcono. Ucwaningo olunzulu lokuvuselela ubuchopho, lapho idivayisi efakwe khona kagesi ivuselela ubuchopho, ibonise ukuthi izimpawu zokucindezeleka zingaguqulwa ngokushesha kakhulu. Okufanayo kwenzeka nezinye izidakamizwa ezifana ne-ketamine, naphezu kwemiphumela emibi kakhulu. Ngakho-ke, kubonakala ngokucacile ukuthola umphumela wokucindezeleka ebuchosheni ngokushesha; kuyisimo nje sokukhomba izifunda ezifanele. Ngokusekelwe kwizifundo ezimbili ezintsha, kubonakala sengathi lezo zifunda zihlala ku-VTA, futhi ikakhulukazi ekuxhumaneni kwayo nucleus accumbens (NA) eseduzane.
Faka: i-dopamine
I-VTA iyisitibe sezinzwa ze-neurons ezifihlakeleyo i-dopamine, enye imakhemikhali yobuchopho ehilelekile emizweni yomvuzo. I-Dopamine ingumdlali omusha kakhulu ocwaningweni lokucindezeleka. Kule minyaka eyishumi edlule, amaqembu ahlukene asebenzise i-dopamine neurons exhuma i-VTA ne-NA futhi ibonakaliswe izimpawu zokucindezeleka ezigundwini.
Amaqembu e-Tye namaChaudhury enza ngokuphumelelayo okufanayo, kodwa ngokucacile kakhulu kunanoma ubani owake waphatha ngaphambilini. Ikhadi labo le-ace laliyindlela ebizwa ngokuthi i-optogenetics, okufaka ama-neurons ane-protini ekhanyayo evumela ukuthi ilawulwe yi-fibre optic. Ngamaprotheni, ososayensi bangakwazi ukuvula noma ukuvala ama-neurons ngemibala ehlukene yokukhanya. Bangakwazi ukukhomba izingxenye ezithile zobuchopho, noma izinhlobo ezithile zeseli. Bangaphenya ubuchopho njenganini ngaphambili (futhi akumangazi ukuthi omunye wabasunguli bezinkampani - uKarl Deisseroth - uveza kokubili amaphepha).
Ithimba likaTye lisebenzisa i-optogenetics ukuthulisa okokuqala i-VTA neurons, okuyinto ngokushesha futhi ngokuphindaphindiwe yenza amagundane avamile aziphathe njengokungathi ayecindezelekile. Ngakolunye uhlangothi, lapho benza ama-neurons afanayo emlilweni ovuthiwe ("phasically"), aphendulela izimpawu ezigundwini ezazicindezelwe ngomoya amasonto.
Iqembu likaHan lisebenzisa i-optogenetics ukukhombisa imiphumela ehlukile emagundeni ayebhekane nokucindezeleka okukhulu "kokuhlukunyezwa komphakathi" kwezinsuku. Lapho benza i-VTA neurons umlilo phasically, izilwane ezinamandla zibonisa izimpawu zokucindezeleka. Lapho bezithulisa lezi zine-neurons ezifanayo, izilwane ezikhukhumezekile zaqina.
Ama-flavour amabili okucindezeleka angase enze izinto ezihlukile, kodwa boba bobabili basebenza kwi-VTA, futhi imiphumela yabo ingahle ishintshwe ngokushesha. "Kufakazela ngokungabonakali ukubaluleka kwesistimu ye-dopamine ekucindezelekeni," kusho u-Yadid. Usola ukuthi ama-anti-depressants ethu asebenza nge-serotonin asebenza ngokungaqondile ngqo emazingeni e-dopamine. Futhi uma kunjalo, ukuqondisa i-dopamine circuits ngokuqondile kufanele kuvelise amandla anamandla, ngokushesha.
"Sibona imiphumela ngokulandelana kwemizuzwana noma imizuzu," kusho uTye. "Lokho kusitshela ukuthi siqondisa izifundazwe eziqondisa ngokushesha izinkinga ezihlobene nokucindezeleka." Kuzo zombili izimo, kwakungeyona nje i-VTA ebalulekile, kodwa ukuxhumana kwayo ne-nucleus accumbens (NA). Izimpawu ezisuka ku-VTA zilawula ukukhululwa kwe-dopamine e-NA, futhi lokho okuthinta ukuziphatha okunjengokucindezeleka.
"Yilokho okulindeleke khona," kusho uTye. Uthemba ukuthi ukulawula lesi sifunda-kungaba nezidakamizwa, noma ngokuvuselela kagesi-kungasenza sibe nezindlela ezingcono zokuphatha ukucindezeleka, okuzosebenza ngokushesha futhi kube nemiphumela emibi embalwa. "Okwamanje, asinayo izidakamizwa ezikhomba izindawo ezithile zobuchopho, kodwa akungaphezu kokucabanga," usho kanje.
References: Tye, Mirzabekov, Warden, Ferenczi, Tsai, Finkelstein, kim, Adhikari, Thompson, Andalman, Gunaydin, Witten & Deisseroth. 2012. I-Dopamine neurons ilinganisa ukufaka ikhodi kwe-neural nokubonisa kokuziphatha okuhlobene nokudana. Imvelo. http://dx.doi.org/10.1038/nature11740
Chaudhury, Walsh, Friedman, Juarez, Ku, Koo, Ferguson, Tsai, Pomeran, Christoffel, Nectow, Ekstrand, Domingo, Mazei-Robison, Mouzon, Lobo, Neve, Friedman., Russo, Deisseroth, Nestler & Han. 2012. Ukulawulwa okusheshayo kokuziphatha okuhlobene nokudangala ngokulawulwa kwe-midbrain dopamine neurons. Imvelo http://dx.doi.org/doi:10.1038/nature11713
I-Dopamine neurons moderate neural encoding kanye nenkulumo yokuziphatha okuhlobene nokudangala
Kay M. Tye, UJulie J. Mirzabekov, UMelissa R. Warden, U-Emily A. Ferenczi, I-Hsing-Chen Tsai, UJoel Finkelstein, USung-Yon Kim, Avishek Adhikari, Kimberly R. Thompson, Aaron S. Andalman, Lisa A. Gunaydin,Ilana B. Writ& Karl Deisseroth
Imvelo (2012) doi: 10.1038 / nature11740
- Ishicilelwe online12 Disemba 2012
Ukudangala okukhulu kubonakaliswa yizimpawu ezahlukahlukene ezibucayi ezibandakanya ukuphelelwa yithemba ne-anhedonia1. Ama-dopamine neurons abandakanyeka emvuzweni nashukumisweni2, 3, 4, 5, 6, 7, 8, 9 ziphakathi kwabantu abaningi be-neural abaye bahlatshwa umqondo ukuthi bafanele10, futhi ezinye izindlela zokwelapha ezibulala amagciwane, kufaka phakathi umuthi nokwelapha ubuchopho, zingathonya uhlelo oluyinkimbinkimbi lwe-dopamine. Kuze kube manje akukwenzeki ukuba kuhlolwe le hypothesis ngqo, noma kumamodeli wezilwane, njengoba ukungenelela okukhona okwelapha kungakwazi ukuqondisa ngqo ama-dopamine neurons. Lapha siphenye ngokuqondile iminikelo yokudalwa kwama-dopamine neurons echazwe kuma-phenotypes amaningi wokucindezelwa okubangelwa ukucindezelwa okungatheni okungapheli, ngokuhlanganisa izindlela zokuziphatha, zamakhemikhali, zeprogenetic kanye ne-electrophysiological ekuhambeni kwamagundane ngokukhululeka. Sithole ukuthi ukulawulwa kwe-bidirectional (inhibition noma i-exciting) ye-midbrain dopamine neurons ecacisiwe ngokushesha nokuguqulwa kwe -ndairectionally (induces noma kukhulula) izimpawu zokuzimela eziningi ezizimele ezibangelwa ukucindezeleka okungapheli. Ngokuphenya ukuqaliswa kokujikeleza kwale miphumela, siphawule ukuthi ukuqashwa kwama-optogenetic kwalezi zimpawu zama-dopamine kuguqula ngokunamandla ukufakwa kwe-neural kokuziphatha okuhlobene nokucindezelwa endaweni ephansi ye-nucleus ye-rodus yokuhambisa ngokukhululekile izinduku, siphakamisa ukuthi izinqubo ezithinta izimpawu zokucindezelwa zingafaka ukuguqulwa kwe-neural ukufaka ikhodi yesenzo kumjikelezo we-limbic.
Okusheshayo umthethonqubo of okuhlobene nokudangala ukuziphatha by isilawuli of midbrain i-dopamine i-neurons.
Nature. I-2012 Dec 12. doi: 10.1038 / nature11713. [Epub phambili ukuphrinta]
Umthombo
I-1] UMnyango we-Pharmacology and Systems Therapeutics, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029, USA [2].
abstract
Indawo ye-Ventral tegmental (VTA) i-dopamine i-neurons esifundeni semivuzo yobuchopho sinendima ebalulekile ekulamuleni izimpendulo zokuxineka, kufaka phakathi ukunquma ukuthambekela nokuqina kokuqina kokuziphatha okubangelwa ukucindezeleka komphakathi. I-VTA i-dopamine i-neurons bonisa ezimbili kumaphethini we-vivo wokudubula: ukudubula okuphansi kwe-tonic kanye nokudubula okukhulu kwe-phasic. Ukudubula okubucayi kwe i-neurons, eyaziwa kahle ukuthi ifaka amasignali emivuzo, ibhaliswa ngokucindezelwa okuphindwayo kokuhlaselwa yinhlalo, imodeli yegundane evunyelwe kakhulu yokuxineka. Ngokumangazayo, lo mphumela we-pathophysiological ubonakala kumagundane atholakala kuphela, ngaphandle koshintsho olubonakalayo lokudubula kwabantu abanamandla. Kodwa-ke, ubufakazi obuqondile-ngesikhathi sangempela sokuxhumanisa i-dopamine ukudubula kwe-neuron phasic ekuthuthukiseni i-phenotype engacashunwa (ukucindezelwa-njenge-phenotype) kuyantuleka. Lapha sisebenzise ithuba ngokunemba kwesikhashana kanye nohlobo lweselula kanye nokuqokwa kwendlela ye-optogenetics ukukhombisa ukuthi ukudubula okuphambili kwalokhu i-neurons kuxazulula ukuthambekela ekucindezelekeni kwenhlalo ekuziphatheni kwamahhala ngokukhululeka. Sibonisa lokho kungeniswa kwe-optogenetic ye-phasic, kepha hhayi tonic, ukudubula ku-VTA i-dopamine i-neurons wezimpisi ezihamba ngaphansi kwepharadigm yokunqotshwa komphakathi yangena ngokushesha into engabonakali njengoba ilinganiswa nokugwemeka komphakathi futhi inciphise ukuthanda kwe-sucrose. Ukugqugquzela kwe-optogenetic phasic kwalezi i-neurons futhi yafaka ngokushesha i-phenotype engabonakala kalula kumagundane abekade ebekezelela leyo eyayicindezelwe kaningi ngokunqotshwa kwenhlalo. Ngaphezu kwalokho, sibonisa umehluko ekucacisweni kwendlela yomgwaqo ekuqhakambiseni ukuthinteka kwengcindezi: ukwenziwa kwe-phasic kwe-VTA i-neurons ukusebenza ku-nucleus accumbens (NAc), kepha hhayi i-medial prefrontal cortex (mPFC), okubangele ukuthinteka kwengcindezi yokuhlulwa komphakathi. Ngakolunye uhlangothi, ukuvimba kwe-optogenetic kokuqagela kwe-VTA-NAc kuholele ekuqineni, kanti ukuvimbela ukuqagela kwe-VTA-mPFC ukuqagela kukhuthaze ukushuba. Sekukonke, lezi zifundo ziveza izindlela zokudubula zenoveli- kanye ne-neural-circuit-fulani izindlela zokudangala.
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