Lifahleho tse peli tsa khatello ea maikutlo - lithuto tse peli li tima matšoao ho litoeba, empa ka tsela tse fapaneng
Mosebetsing ho la univesithi ea Stanford, toeba e bontša matšoao a khatello ea maikutlo. Bakeng sa libeke tsa 10 tse pota-potileng, e bile le letoto la lintho tse khopisang, ho tloha ka linako tse ling ntle le lijo kapa metsi, ho latela mekhoa e metle ea ho robala. Hona joale, sepheo sa eona se tlase - ha e huloa ke mohatla, e leka makhetlo a 'maloa ho baleha,' me ha e leke ho hlahloba libaka tse ncha. Ha e na boikemisetso bo fokolang ba ho noka lero le tsoekere - pontso ea hore e ha e natefeloe ke mesebetsi e tloaelehileng. Ha ho mohla ho leng bonolo ho lekola bophelo ba kelello ba phoofolo, empa panya ena e bonts'a matšoao a hlakileng a khatello ea maikutlo.
Empa eseng nako e telele.
Pejana, Kay Tye 'me Julie Mirzabekov e fetotse toeba e le hore khanya ea khanya e ka kenya letsoho karolo e nyane ea bokong ba eona sebaka sa ventral tegmental (VTA), haufi le tlase ho bokong hape haufi le midline. Ho phatloha ho hoholo, le boitšoaro ba panya bo fetoha hang hang. E loana ka thata ha e tšoarelle holimo, e phenyekolla libaka tse bulehileng, 'me e boela e fumana leino le monate. Ho phatloha ha khanya, le matšoao a eona oa nyamela.
Empa lehlakoreng le leng la naha, Sekolong sa Bongaka sa Mount, Dipesh Chaudhury le Jessica Walsh ba etsa ntho e ts'oanang ho fapana ka botlalo. Litoeba tsa bona li fetotsoe ka tsela e tšoanang, e le hore leseli le khone ho bulela li-neuron tsa bona tsa VTA. Empa litoeba tsena li mamelletse mofuta o khuts'oane empa o matla haholo oa khatello ea maikutlo-Matsatsi a 10 a ho kenngoa ka har'a mekotla e nang le bahanyetsi ba matla, ba mabifi. Ka lebaka la litlhaselo tse ileng tsa baka, ba bang ba bona ba bile le matšoao a sithabetsang. Ba bang ba mamella haholoanyane. Empa ha Chaudhury le Walsh ba bonesa li-VTA tsa tsena litoeba, batho ba bang ba matla le ba ho feto-fetoha le maemo ba fetotsoeng.
Ka bobeli lithuto li sebelisitse mekhoa e ts'oanang ho baka li-neuron karolong e ts'oanang ea boko ... mme li bile le litlamorao tse fapaneng ka ho felletseng. Teko ea Tye le Mirzabekov, litoeba tse tepelletseng maikutlo li ile tsa qalella boits'oaro ba tsona bo tloaelehileng. Thutong ea Chaudhury le Walsh, litoeba tse tiisitsoeng li bontšitse Hape matšoao a sithabetsang.
Litsela tse ngata tsa khatello ea maikutlo
Lihlopheng ka bobeli li nahana hore liphetho tse hlakileng tse hanyetsanang li bakoa ke mefuta e fapaneng ea khatello ea maikutlo e fumanoang ke litoeba. Liphoofolo tsa Tye li ile tsa ba le khatello e matla ea maikutlo joalo ka motho ha a tobane le ts'ireletso e sa feleng mosebetsing. Litsuonyana tsa Chaudury le Walsh li ile tsa tobana le khatello e matla ea "ho hlotsoa sechabeng" ka nako e khuts'oane, e batlang e tšoana le motho ea ts'oaroang. Liphihlelo tsena tse fapaneng li ka susumetsa likarolo tse tšoanang tsa kelello, empa li etsa joalo ka litsela tse fapaneng. Ming-Hu Han, ea neng a etelletse thuto ea bobeli pele, o re: “Motho e mong le e mong o na le nalane ea hae ea bophelo, 'me o thulana le khatello ea maikutlo le likotsi tse fapaneng. E ka 'na eaba ke hobane'ng ha u bapisa matšoao a ho batho ba babeli ba nang le khatello ea maikutlo, ba fapaneng. ”
Liphetho li totobatsa mofuta o rarahaneng oa khatello ea maikutlo. E na le lisosa tse ngata tse ka sebetsang bokong ka litsela tse fapaneng, leha li ka susumetsa sebaka se le seng, le ho hlahisa matšoao a tšoanang.
Sena se ka boela sa hlalosa hore na hobaneng ho se na kalafo e boholo bo lekanang - kaofela ha khatello ea khatello ea maikutlo. Tye, eo hona joale a itlhomelletseng lebokoseng la Massachussetts Institute for Technology o re: “Le lithethefatsi tse sebetsang hantle feela li sebetsa bakeng sa ntho e itseng e tlaase. Patlisiso mabapi le li-antidepressants e bile… hantle… e sithabetsang maikutlo hanyane. Leha e le nalane ea lilemo tse hlano, ho entsoe tsoelo-pele e fokolang lilemong tse leshome tse fetileng. O re: "Lilemong tse 500 tse fetileng, ha ho tsoelo-pele e tebileng e kileng ea etsoa." Gal Yadid ho tsoa Univesithing ea Bar-Ilan Iseraele.
Empa lithuto tsena tse ncha, leha li ne li etsoa ka litoeba, li fana ka lintlha tse ngata tse ka lebisang ho kalafo tse ncha. Li supa likarolo tsa boko tse kenyelletsang matšoao, li bonts'a hore matšoao ao a ka khutlisetsoa kapele, mme a re joetsa haholoanyane ka lik'hemik'hale tse amehang.
Boholo ba maqhubu a hona joale a li-antidepressants, joalo ka Prozac, li eketsa serotonin ea lik'hemik'hale tsa boko, motheong oa hore maemo a tlase a lebisa khatello ea maikutlo. Empa khopolo-taba ena e ke ke ea nepahala. Qalong, meriana ena ha e sebetse motho e mong le e mong. Ha li sebetsa, li ka nka likhoeli tse ngata ho kena. Haeba lithethefatsi li ne li sebetsa hobane li eketsa maemo a serotonin, li lokela ho sebetsa lihora tse ngata. Joalo, ho bonahala eka ba sebetsa ka mokhoa o sa laoleheng.
Re ka etsa betere. Liphuputso tse nang le tšusumetso e matla bokong, moo sesebelisoa se kentsoeng ka motlakase se hlasimollang boko, se bonts'itse hore matšoao a khatello ea maikutlo a ka fetoha hape kapele haholo. Ho etsahala se tšoanang le ka lithethefatsi tse ling tse kang ketamine, le litlamorao tse mpe. Kahoo, ho hlakile hore ho ka ba le phello e khahlanong le khatello ea kelello bokong kapele haholo; ke taba feela ea ho shebisisa lipotoloho tse nepahetseng. Ho ipapisitsoe le lithuto tse peli tse ncha, ho bonahala eka literaka tseo li lula VTA, 'me ka ho khetheha lihokahaneng tsa eona li na le li-nucleus accumbens (NA) tse haufi.
Enter: dopamine
VTA ke sebui sa neurons se sephiring dopamine, k'hemik'hale e 'ngoe ea boko e kenyelletsang maikutlo a moputso. Dopamine ke sebapali se secha sa lipatlisiso tsa khatello ea maikutlo. Lilemong tse leshome tse fetileng, lihlopha tse fapaneng li thetsitse methapo ea kutlo ea dopamine e hokahanyang VTA le NA mme li hlahisitse matšoao a khatello ea maikutlo ho litoeba.
Lihlopha tsa Tye le Chaudhury li entse hantle ka mokhoa o ts'oanang, empa ka mokhoa o nepahetseng ho feta leha e le ofe o kileng oa atleha. Karete ea bona ea ace e ne e le mokhoa o bitsoang optogenetics, e kenyang li-neuron ka liprotheine tse bobebe tse li lumellang hore li laoloe ke likhoele tsa optic. Ka liprotheine tsena, bo-rasaense ba ka bulela kapa ba tima ka mebala e fapaneng ea khanya. Li ka lebisa likarolo tse itseng tsa boko, kapa mefuta e khethehileng ea sele. Ba ka etsa lipatlisiso tsa boko ho feta leha e le neng pele ('me ha ho makatse hore e mong oa baqapi ba mokhoa ona - Karl Deisseroth - likarolo tse fumanehang lipampiring ka bobeli).
Sehlopha sa Tye se sebelisitse optogenetics ho khutsisa li-neurons tsa VTA, tse ileng tsa etsa joalo hang-hang hape ka mokhoa o fetohileng joalo ka ha eka li sithabetse maikutlo. Ka lehlakoreng le leng, ha ba ne ba etsa mollo o tšoanang oa li-neuron ka ho phatloha khafetsa ("phasically"), ba ne ba khutlisa matšoao a litoeba tse neng li hatelletsoe butle ka libeke.
Sehlopha sa Han se sebelisitse optogenetics ho bonts'a litlamorao tse mpe tsa litoeba tse neng li bile le khatello ea maikutlo ea "ho hlola setjhaba" ka matsatsi. Ha li etsa hore li-neurons tsa VTA li tuke ka mokhoa o hlakileng, liphoofolo tse mamellang li ile tsa bonts'a matšoao a kang a khatello ea maikutlo. Ha li khutsisa lisele tse tšoanang, liphoofolo tse kotsing ea ho fetoha lia tsofala.
Litlamorao tse peli tsa khatello ea maikutlo li kanna tsa etsa lintho tse fapaneng, empa li sebetsa ho VTA, 'me litlamorao tsa tsona li ka khutlisoa hanghang. Yadid o re: "Ho paka ntle ho moelelo bohlokoa ba sistimi ea dopamine ho tepella maikutlong." O belaela hore li-antidepressants tsa rona tsa serotonin-boosting li sebetsa ka ho ama ka kotloloho maemo a dopamine. Mme haeba ho le joalo, joale ho lebisa lipotoloho tsa dopamine ka kotloloho ho lokela ho hlahisa litlamorao tse matla, kapele.
Tye o re: “Re bona lintho ka ho latellana ha metsotsoana kapa metsotso. "Seo se re joetsa hore re shebile lipotoloho tse otlolohileng tse laolang matšoao a amanang le khatello ea maikutlo hanghang." Maemong ana ka bobeli, e ne e se VTA feela e amanang le eona, empa e le khokahano ea eona ho nucleus accumbens (NA). Matšoao a VTA a laolang ho ntšoa ha dopamine ho NA, le hore ka lehlakoreng le leng e ama boits'oaro bo kang khatello ea maikutlo.
Tye o re: “Ke sona seo re se shebiloeng hona joale. O ts'epa hore ho laola potoloho ena - ebang ke lithethefatsi, kapa ka ho tsosa ka motlakase-ho ka re lebisa ho mekhoa e metle ea ho phekola khatello ea maikutlo, e neng e tla sebetsa ka potlako haholo mme e be le litlamorao tse fokolang. O re: "Hajoale, ha re na lithethefatsi tse lebisang likarolo tse itseng tsa boko, empa re ke ke ra li nahana."
References: Tye, Mirzabekov, Warden, Ferenczi, Tsai, Finkelstein, kim, Adhikari, Thompson, Andalman, Gunaydin, Witten & Deisseroth. 2012. Dopamine neurons modulate neural encoding le polelo ea boitšoaro bo amanang le khatello ea maikutlo. Tlhaho. 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. Taolo e potlakileng ea boits'oaro bo amanang le khatello ea maikutlo ka taolo ea midbrain dopamine neurons. Tlhaho http://dx.doi.org/doi:10.1038/nature11713
Dopamine neurons e feto-fetohe ho kopanya ha neural le polelo ea boitšoaro bo amanang le khatello ea maikutlo
Kay M. Tye, Julie J. Mirzabekov, Melissa R. Warden, Emily A. Ferenczi, Hsing-Chen Tsai, Joel Finkelstein, Sung-Yon Kim, Avishek Adhikari, Kimberly R. Thompson, Aaron S. Andalman, Lisa A. Gunaydin,Ilana B. E hlotseng& Karl Deisseroth
Tlhaho (2012) doi: 10.1038 / nature11740
- E phatlalalitsoe online12 December 2012
Ho tepella maikutlo ho hoholo ho tšoauoa ka matšoao a fapa-fapaneng a fokolisang a kenyang ho hloka tšepo le anhedonia1. Dopamine li-neurons tse amehang moputsong le tšusumetso2, 3, 4, 5, 6, 7, 8, 9 li har'a lipalo tse ngata tsa neural tse boletsoeng hore li nepahetse10, le mekhoa e meng ea kalafo ea meriana e loantšang khatello ea maikutlo, ho kenyelletsa le litlhare le litlhare tse khothatsang tsa boko, li ka susumetsa sistimi e rarahaneng ea dopamine. Ho fihlela hajoale ha ho a ka ha khoneha ho leka hypothesis ena ka kotloloho, esita le mehlaleng ea liphoofolo, kaha mekhoa ea phekolo e teng e sa khone ho tobisa kannete li-dopamine neurons. Mona re fuputse ka kotloloho monehelo oa causal oa "dopamine neurons" o hlalositsoeng ka khatello ea maikutlo ka bongata ka ho fetesisa khatello ea maikutlo, ka ho hokahanya mekhoa ea boits'oaro, ea meriana, ea optogenetic le ea electrophysiological metsong e tsamaeang ka bolokolohi. Re hlokometse hore taolo ea concirectional (inhibition or excitation) ea "midbrain dopamine neurons" e potlakileng le li-modirectionally modulates (induces kapa relieves) matšoao a mangata a ikemetseng a khatello ea maikutlo a bakiloeng ke khatello ea maikutlo e sa foleng. Ka ho hlahloba ts'ebetso ea potoloho ea litlamorao tsena, re hlokometse hore ho haptjoa ha li-optogenetic tsa "dopamine neurons" hantle ho fetola mokhoa o kopantsoeng oa boits'oaro bo amanang le khatello ea maikutlo mokhoeng o ka tlase oa methapo ea methapo e tsamaeang ka bolokolohi, ho fana ka maikutlo a hore lits'ebetso tse amang matšoao a khatello ea maikutlo li ka kenyelletsa liphetoho tsa tlhaho encoding of Ketso ea maoto le matsoho.
Ka potlako molao oa tsamaiso of amanang le khatello ea maikutlo boitšoaro by ho laola boemo of midbrain dopamine neurons.
Nature. 2012 Dec 12. Doi: 10.1038 / nature11713. [Epub pele условия:]
mohloli o moholo
1] Lefapha la Pharmacology and Systems Therapeutics, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029, USA [2].
inahaneloang
Sebaka sa Ventral tegmental (VTA) dopamine neurons potolohong ea moputso ea boko e na le karolo ea bohlokoa ho feliseng likarabo tsa khatello ea maikutlo, ho kenyeletsoa ho khetholla ts'oaetso khahlanong le boits'oaro ba boits'oaro bo bakoang ke khatello ea maikutlo. VTA dopamine neurons bonts'a tse peli ho mekhoa ea vivo ea ho thunya: ho thunya hangata ha tonic le ho thunya hangata ha phasic. Phasic fired of neurons, e tsebahalang ho kenyelletsa matšoao a meputso, e khothatsoa ke khatello ea maikutlo ea ho hlola setjhaba khafetsa, mohlala o hlakileng oa panya ea khatello ea maikutlo. Ho makatsang ke hore, phello ena ea pathophysiological e bonoa ho litoeba tse senyehang habonolo, ntle le phetoho e hlakileng ea sekhahla sa ho thunya ho batho ba tiileng. Leha ho le joalo, bopaki bo tobileng-ka nako ea 'nete bo hokahanya dopamine ho thunya ha neuron phasic ho nts'etsapele mofuta oa phenotype o hlasetsoeng (khatello ea maikutlo-joalo) oa fokola. Mona re sebelisitse monyetla oa ho nepahala ha nakoana le mofuta oa sele le mofuta oa tsela ea liketsahalo tsa "optogenetics" ho bonts'a ho fokotseha ha phasic ea tsena neurons buella ho ba le khatello ea maikutlo ea ho hlola setsoalle litabeng tsa boitšoaro bo lokolohileng. Re bonts'a ts'ebetso ea optogenetic ea phasic, empa eseng tonic, e thunya ho VTA dopamine neurons litoeba tse tlisoang ke paradigm e felisang boemo ba sechaba ka potlako e ile ea tsosa mofere-fere habonolo joalo ka ha e lekantsoe ke ho qoba sechaba le ho fokotsa ho rata. Optogenetic phasic e susumetsang ea neurons hape a potlakisa ho tsosa mofere-fere oa mofuta oa litheko tsa pele tse neng li le tlas'a khatello ea khahlano le sechaba khafetsa. Ntle le moo, re bonts'a liphapang tse ikhethang tsa tsela ea projeke ea ho ntšetsa pele khatello ea khatello ea maikutlo: ts'ebetso ea phasic ea VTA neurons projeketso ea ho bokellana ka methapo (NAc), empa eseng ho medial prefrontal cortex (mPFC), e bakileng pherekano ea khatello ea khatello ea maikutlo ea sechaba. Ka lehlakoreng le leng, thibelo ea optogenetic ea projeke ea VTA-NAc e ile ea etsa hore motho a tiise, ha thibelo ea projeke ea VTA-mPFC e khothalelitse bofokoli. Ka kakaretso lithuto tsena li senola mekhoa ea ho thunya e nooang hangata le mekhoa e ikhethileng ea ho tepella maikutlong.
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