Kuthetha ntoni i-dopamine? (2018)

. Umbhalo obhaliweyo ifumaneka kwi-PMC 2019 Feb 1.
Ishicilelwe kwifomu yokugqibela ehleliweyo njenge:
Nat Neurosci. 2018 Jun; 21(6): 787–793.

Ishicilelwe kwi-intanethi 2018 Meyi 14. ikhonkco: 10.1038 / s41593-018-0152-y

PMCID: PMC6358212
NIHMSID: NIHMS987662
PMID: 29760524
Josh Berke

Abstract

I-Dopamine sisimodyuli esibalulekileyo sokufunda kunye nenkuthazo. Oku kunika ingxaki: zingazi njani iiseli ekujoliswe kuzo ukuba ukonyuka kwe-dopamine luphawu lokufunda, okanye ukuhamba? Kuhlala kucingelwa ukuba inkuthazo ibandakanya utshintsho olucothayo ("tonic") lwe-dopamine, ngelixa ukukhawuleza ("phasic") ukuguquguquka kwe-dopamine kuhambisa iimpazamo zokuqikelela umvuzo wokufunda. Nangona kunjalo izifundo zamva nje zibonise ukuba i-dopamine idlulisela ixabiso lenkuthazo, kwaye ikhuthaza intshukumo, nokuba kumaxesha angaphantsi kwesibini. Apha ndichaza enye iakhawunti yendlela i-dopamine elawula ngayo indlela yokuziphatha eqhubekayo. Ukukhutshwa kwe-Dopamine okunxulumene nenkuthazo kutyhilwa ngokukhawuleza nasekhaya zii-receptors kwii-terminals ze-dopamine, ngokuzimeleyo kukudubula kweeseli ze-dopamine. Ii-neurons ekujoliswe kuzo zitshintsha ngequbuliso phakathi kweendlela zokufunda kunye nokusebenza, kunye ne-striatal cholinergic interneurons ebonelela ngomatshini omnye wokutshintsha umviwa. Impembelelo yokuziphatha ye-dopamine iyahluka ngokwendawo ephantsi, kodwa kwimeko nganye i-dopamine ibonelela ngoqikelelo oluguquguqukayo lokuba kufanelekile na ukuchitha isixhobo sangaphakathi esilinganiselweyo, njengamandla, ingqalelo, okanye ixesha.

Ngaba i-dopamine luphawu lokufunda, lwenkuthazo, okanye zombini?

Ukuqonda kwethu i-dopamine kutshintshile kwixesha elidlulileyo, kwaye kuyatshintsha kwakhona. Omnye umahluko obalulekileyo uphakathi kweziphumo ze-dopamine yangoku ukuziphatha (ukusebenza), kunye neziphumo ze-dopamine kwi ikamva ukuziphatha (ukufunda). Zombini ziyinyani yaye zibalulekile, kodwa ngamaxesha ahlukahlukeneyo omnye ebekholiswa yaye omnye akayithandi.

Xa (kwi-'70s) kwenzeka ukuba kwenziwe ukhetho, izilonda ezipheleleyo zeendlela ze-dopamine, isiphumo esicacileyo sokuziphatha yaba kukuncitshiswa okukhulu kwentshukumo.. Oku kuhambelana neziphumo ze-akinetic zokulahleka kwe-dopamine ebantwini, eveliswa sisifo sikaParkinson, iziyobisi eziyityhefu, okanye i-encephalitis.. Ukanti iimpuku okanye iimeko zabantu azibonakalisi ukungakwazi ukuhamba. Iimpuku ezinezilonda zeDopamine zidada emanzini abandayo, kunye nezigulane ze-akinetic zinokuvuka kwaye zibaleke ukuba i-alamu yomlilo iyakhala ("i-paradoxical" kinesia). Kwaye akukho ntsilelo esisiseko yokuxabisa imivuzo: iimpuku ezine-dopamine-lesioned ziyakutya ukutya okubekwe emlonyeni wazo, kwaye zibonise iimpawu zokuyonwabela.. Endaweni yoko, abayi kukhetha ukwenza umzamo wokufumana umvuzo. Ezi kunye nezinye iziphumo ezininzi ziseke ikhonkco elisisiseko phakathi kwe-dopamine kunye nenkuthazo. Nokuba intshukumo icothayo ejongwa kwiimeko ezingamandundu kakhulu zeSifo sikaParkinson kunokubonwa njengentsilelo ekhuthazayo, ebonisa izigqibo ezicacileyo zokuba akufanelekanga ukuchitha amandla afunekayo kwiintshukumo ezikhawulezayo..

Emva koko (kwi-'80s) kwafika ukurekhodwa kobuvulindlela be-dopamine neurons ekuziphatheni iinkawu (kwiindawo eziphakathi kwe-midbrain eprojekthi ye-forebrain: indawo ye-ventral tegmental, VTA / substantia nigra pars compacta, SNc). Phakathi kweepateni zokudubula eziqwalaselweyo yaba kukugqabhuka okufutshane komsebenzi okuvuselelayo okubangele intshukumo ekhawulezileyo. Le "phasic" dopamine yokudubula yatolikwa njengenkxaso "yokuvula indlela yokuziphatha" kunye "novuselelo olukhuthazayo" – ngamanye amazwi, njengokuvuselela isimilo sangoku sesilwanyana.

Utshintsho olukhulu lwenzekile ngeminyaka yee-'90s, kunye nokutolikwa kwakhona kwe-phasic dopamine bursts njengokufakwa kweekhowudi. iimpazamo zokuqikelela umvuzo (ii-RPEs). Oku bekusekwe kuqwalaselo oluphambili: iiseli ze-dopamine ziphendula kwisivuseleli esingalindelekanga esinxulunyaniswa nomvuzo wekamva, kodwa zihlala ziyeka ukuphendula ukuba ezi zivuseleli zilindelekile.. Uluvo lwe-RPE lwavela kwiithiyori zokufunda zangaphambili, kwaye ngakumbi kwinkalo yophuhliso lwesayensi yekhompyuter. Inqaku lophawu lwe-RPE kukuhlaziya amaxabiso(uqikelelo lwemivuzo yexesha elizayo). La maxabiso asetyenziswa kamva, ukunceda ukwenza ukhetho olwandisa umvuzo. Kuba ukudutyulwa kweeseli ze-dopamine kufana nee-RPE, kwaye ii-RPE zisetyenziselwa ukufunda, kuye kwangokwemvelo ukugxininisa indima ye-dopamine ekufundeni. Kamva i-optogenetic manipulations yaqinisekisa isazisi se-dopaminergic yeeseli ze-RPE-coding, kwaye babonise ukuba ngokwenene bamodareyitha ukufunda,.

Umbono wokuba i-dopamine ibonelela ngomqondiso wokufunda uhambelana kakuhle noncwadi oluthi i-dopamine imodareyithe iplastiki ye-synaptic kwi-striatum, eyona nto iphambili ekujoliswe kuyo kwi-dopamine. Umzekelo, ukuhlangana kathathu kwe-glutamate yokuvuselela i-striatal dendrite spine, i-postsynaptic depolarization, kunye nokukhululwa kwe-dopamine kubangela ukuba umnqonqo ukhule.. Ukumodareyitha kweDopaminergic kweendlela zokufunda ixesha elide kunceda ekuchazeni iziphumo eziqhubekayo zokuziphatha kweziyobisi ezikhobokisayo, ezabelana ngepropathi yokuphucula ukukhutshwa kwe-striatal dopamine.. Nokuba i-akinesia enzulu enelahleko ye-dopamine inokuchazwa ngokuyinxenye kwezo ndlela zokufunda. Ukunqongophala kwe-dopamine kunokuphathwa njenge-RPE ehlala ingalunganga, ehlaziya ngokuthe ngcembe amaxabiso ezenzo ukuya ku-zero. Iziphumo ezifanayo eziqhubekayo, ezinjengokuphela kokuziphatha zinokuveliswa ngabachasi be-dopamine,.

Nangona kunjalo imbono yokuba i-dopamine ibandakanyeka ngokubalulekileyo kwinkuthazo eqhubekayo ayizange imke - ngokuchaseneyo, ithathwa njengento eqhelekileyo zizazinzulu zokuziphatha. Oku kufanelekile xa kunikwe ubungqina obuqinileyo bokuba imisebenzi ye-dopamine kwinkuthazo / intshukumo / yokuvuselela iyahlukaniseka ekufundeni.,-. Okungaxatyiswanga kakhulu ngumceli mngeni obandakanyekayo ekulungelelaniseni le ndima yenkuthazo kunye nethiyori yokuba iDA ibonelela ngophawu lokufunda lweRPE.

Inkuthazo "ijonge phambili": isebenzisa iingqikelelo zomvuzo wexesha elizayo (amaxabiso) ukunika amandla ngokufanelekileyo indlela yokuziphatha yangoku. Ngokwahlukileyo koko, ukufunda “kujonge ngasemva” kumazwe nakwizenzo zamva nje, kwaye kuhlaziywe amaxabiso azo. Ezi zizigaba ezihambelanayo zomjikelo: amaxabiso ahlaziyiweyo anokusetyenziswa ekwenziweni kwezigqibo okulandelayo ukuba loo mazwe aphinde adibana, emva koko ahlaziywe kwakhona, njalo njalo. Kodwa sesiphi isigaba somjikelo i-dopamine ebandakanyekayo - usebenzisa amaxabiso ukwenza izigqibo (ukusebenza), okanye ukuhlaziya amaxabiso (ukufunda)?

Kwezinye iimeko kuthe tye ukucinga ukuba i-dopamine idlala zombini iindima ngaxeshanye.Okungalindelekanga, okuxelwe kwangaphambili komvuzo ziziganeko zakudala zokuvusa ukudubula kweseli ye-dopamine kunye nokukhululwa, kwaye ezo mpawu zihlala zombini zivuselela kwaye zivuselele ukufunda (Ikhiwane. 1). Kule meko ikhethekileyo kokubini ukuxela kwangaphambili umvuzo, kunye neempazamo zokuxela kwangaphambili umvuzo, zonyuka ngaxeshanye - kodwa oku akusoloko kunjalo. Njengomzekelo nje omnye, abantu nezinye izilwanyana badla ngokushukunyiselwa ukuba basebenzele imivuzo nangona kuncinane okanye kungekho nto ingako imangalisayo eyenzekayo. Basenokusebenza nzima nangakumbi njengoko besondela ngokusondela emvuzweni (ixabiso liyakhula njengoko imivuzo isondela). Inqaku lelokuba ukufunda kunye nenkuthazo kunengqondo, ngokubala, kunye nokuziphatha kwahlukile-kwaye i-dopamine ibonakala izenza zombini.

Ifayile yangaphandle ephethe umfanekiso, umzekeliso, njl njl igama le-nihms-987662-f0001.jpg

I-Dopamine: ukuhlaziya ixesha elidlulileyo, ukuvuselela okwangoku.

umphezulu, Izangqa ezineentolo zimele amazwe kunye neentshukumo ezinokubakho ukusuka kwezo zizwe. Ububanzi botolo bubonisa amaxabiso afundiweyo okwenza isenzo ngasinye. Njengoko amazwe/izenzo ziphela kwixesha elidlulileyo, ngokuthe ngcembe azifanelekanga ukuba ziqiniswe. Ephakathi, ukuqhuma kwe-dopamine kwenzeka. Isiphumo kukukhuthazwa kwezenzo ezikhoyo kwimeko yangoku (obomvu), kunye neplastiki yexabiso lokubonakaliswa kwezenzo ezisandul 'ukwenziwa (omfusa). ezantsi, njengesiphumo seplastiki, ngexesha elizayo ezi zizwe zidibana namaxabiso ahambelanayo anyukile (ububanzi botolo). Ngokufunda ngokuphindaphindiweyo ukomeleza ukufunda “kunokuchwela umqolo” kwisithuba sombuso, kwenze ukuba iindlela ezithile zihambelane ngakumbi. Ukongeza kule ndima yokufunda, indima ekhuthazayo, yokusebenza kwe-dopamine ibonakala ikhawulezisa ukuhamba ngeendlela ebezifundwe ngaphambili.

Apha ngezantsi ndivavanya ngokunzulu izimvo zangoku malunga nendlela i-dopamine ekwazi ngayo ukufezekisa imisebenzi yokufunda kunye nenkuthazo. Ndicebisa imodeli ehlaziyiweyo, esekwe kwiinyani ezintathu eziphambili: 1) ukukhutshwa kwe-dopamine kwii-terminals akuveli nje ngokudubula kweeseli ze-dopamine, kodwa kunokulawulwa ekuhlaleni; 2) i-dopamine ichaphazela zombini iplastiki ye-synaptic kunye nokonwaba kweeseli ekujoliswe kuzo, ezineziphumo ezahlukileyo zokufunda nokusebenza ngokulandelelanayo; 3) Iziphumo ze-dopamine kwiplastiki zinokuvulwa okanye zicinywe zizinto zesekethe ezikufutshane. Ngokudibeneyo, ezi mpawu zinokuvumela iisekethe zobuchopho ukuba zitshintshe phakathi kwemiyalezo emibini eyahlukeneyo ye-dopamine, yokufunda kunye nenkuthazo ngokulandelelanayo.

Ngaba zikhona izibonakaliso ze-dopamine "ze-phasic" kunye ne "tonic", ezineentsingiselo ezahlukeneyo?

Kuhlala kuxoxwa ukuba iindima zokufunda kunye nenkuthazo ye-dopamine zenzeka kwizikali zamaxesha ahlukeneyo. Iiseli ze-Dopamine zivutha ngokuqhubekayo ("tonic") kwi-spikes ezimbalwa ngesekhondi, ngamanye amaxesha okufutshane ("phasic") ugqabhuko okanye unqumame. Ukugqabhuka, ngakumbi ukuba kulungelelaniswa ngokwendalo kwiiseli ze-dopamine, ukuqhuba okuhambelana nokunyuka okukhawulezileyo kwi-forebrain dopamine. ezidlulayo kakhulu (ixesha elingaphantsi kwesibini). Igalelo elahlukileyo lokudubula kweseli ye-tonic dopamine kwi-forebrain dopamine concentrations ayicacanga kangako. Obunye ubungqina bubonisa ukuba eli galelo lincinci kakhulu. Inokwanela ukuvelisa uvuselelo olusondeleyo lwe-D2 receptors ephezulu, evumela inkqubo ukuba ibone ukunqumama okufutshane ekudubuleni kweeseli ze-dopamine. kwaye usebenzise oku nqumama njengeempazamo zokuxela kwangaphambili okungalunganga.

I-Microdialysis isetyenziswe ngokubanzi ukulinganisa ngokuthe ngqo amanqanaba e-forebrain dopamine, nangona kukho isisombululo sexesha eliphantsi (ngokuqhelekileyo i-avareji kwimizuzu emininzi). Imilinganiselo ecothayo enjalo ye-dopamine inokuba ngumngeni ukunxulumana ngokuchanekileyo nokuziphatha. Nangona kunjalo i-microdialysis ye-dopamine kwi-nucleus accumbens (NAc; i-ventral / i-medial striatum) ibonisa ulungelelwaniso oluhle lomsebenzi we-locomotor. kunye nezinye iimpawu zenkuthazo. Oku kuthathwa ngokubanzi ukuba kuthetha ukuba kukho utshintsho olucothayo ("tonic") kugxininiso lwe-dopamine, kwaye olu tshintsho lucothayo lugqithisa uphawu olukhuthazayo. Ngokuthe ngqo, iimodeli zokuhlanganisa zicebise ukuba amanqanaba e-tonic dopamine alandele umndilili wexesha elide lomvuzo – inguqu eluncedo yenkuthazo yokwabiwa kwexesha kunye nezigqibo zokufuna ukutya. Kuyafaneleka ukugxininisa ukuba amaphepha ambalwa kakhulu achaza ngokucacileyo amanqanaba e-dopamine "e-tonic" - bahlala becinga ukuba ugxininiso lwe-dopamine lutshintsha kancinci kwimizuzu emininzi yexesha le-microdialysis.

Ukanti le “phasic dopamine=RPE/learning, tonic dopamine=motivation” ijongana neengxaki ezininzi. Okokuqala, akukho bungqina buthe ngqo bokuba ukudubula kweseli ye-tonic dopamine ngokuqhelekileyo kuyahluka kwizikali zexesha elicothayo. Amazinga okudubula kwe-Tonic awatshintshi ngokutshintsha inkuthazo,. Kuye kwaxoxwa ukuba amanqanaba e-tonic dopamine ayatshintsha ngenxa yokutshintsha kwenani leeseli ze-dopamine ezisebenzayo,. Kodwa kwizifundo ezininzi kwizilwanyana ezingathotywanga, ezingafakwanga, iiseli ze-dopamine azizange zixelwe ukuba zitshintshe phakathi kwamazwe athuleyo nasebenzayo.

Ngaphaya koko, into yokuba i-microdialysis ilinganisa amanqanaba e-dopamine ngokuthe chu ayithethi ukuba amanqanaba e-dopamine atshintsha kancinci. Thina mva nje ivavanye ibuzi i-NAc dopamine kumsebenzi onokwenzeka womvuzo, usebenzisa zombini i-microdialysis kunye ne-scan-scan cyclic voltammetry. Siye saqinisekisa ukuba i-mesolimbic dopamine, njengoko ilinganiswe yi-microdialysis, ihambelana nezinga lomvuzo (imivuzo/min). Nangona kunjalo, kunye nesisombululo sexeshana esiphuculweyo se-microdialysis (1min) i-dopamine iguquguquka ngokukhawuleza njengoko siyisampula: asibonanga bungqina bomqondiso we-dopamine ocothayo.

Sisebenzisa isisombululo sexeshana esigqwesileyo se-voltammetry siye sabona ubudlelwane obusondeleyo phakathi kokuguquguquka kwe-dopamine kunye nenkuthazo. Njengoko iimpuku zenze ulandelelwano lwezenzo ezifunekayo ukufumana umvuzo, i-dopamine yenyuka yaya phezulu, yafikelela encotsheni kanye njengoko zifumana umvuzo (kwaye zehla ngokukhawuleza njengoko beziyidla). Sibonise ukuba i-dopamine inxibelelene kakhulu nexabiso lelizwe elikhawulezayo-elichazwa njengomvuzo olindelweyo wekamva, uthotywe ngexesha elilindelweyo lokuwufumana. Ezi ntshukumo zikhawulezayo ze-dopamine zinokuchaza iziphumo ze-microdialysis, ngaphandle kokubiza imiqondiso eyahlukeneyo ye-dopamine kwizikali zexesha ezahlukeneyo. Njengoko izilwanyana zifumana imivuzo engakumbi, zonyusa ulindelo lwazo lwemivuzo yexesha elizayo kwinyathelo ngalinye kulandelelwano lolingo. Endaweni yokuvela komndilili womvuzo ovela kancinci, ulungelelwaniso phakathi kwe-dopamine kunye nenqanaba lomvuzo lichazwa ngcono njengomndilili, ngaphezulu kwexesha elide lokuqokelelwa kwesampulu ye-microdialysis, kula maxabiso karhulumente avela ngokukhawuleza.

Le toliko yexabiso yokukhutshwa kwe-mesolimbic dopamine iyahambelana neziphumo zevoltammetry ezivela kwamanye amaqela ophando, abaye bafumanisa ngokuphindaphindiweyo ukuba i-dopamine ikhupha i-ramps up kunye nokwandisa ukusondela ekuvuzeni.-(Ikhiwane. 2). Lo mqondiso wenkuthazo awukho “cotha” ngokwendalo, kodwa unokubonwa kuluhlu oluqhubekayo lwezikali zexesha. Nangona iirampu ze-dopamine zinokuhlala imizuzwana emininzi xa indlela yokuziphatha nayo ithatha imizuzwana emininzi, oku kubonisa ikhondo lexesha lokuziphatha, endaweni ye-intrinsic dopamine dynamics. Ubudlelwane phakathi kokukhutshwa kwe-mesolimbic dopamine kunye nexabiso eliguquguqukayo libonakala ngokukhawuleza njengoko ubuchule bokurekhoda buvuma, okt kwi ~ 100ms isikali sexesha kunye ne-acute voltammetry electrode..

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Ukuguquguquka okukhawulezileyo kwe-dopamine kuphawu oluguqukayo olulindelekileyo lomvuzo.

ac) Ukukhutshwa kwe-Mesolimbic dopamine konyuka ngokukhawuleza njengoko iimpuku zisondela kwimivuzo elindelweyo. d) Ixabiso, elichazwa njengoqikelelo oluthotywe okwethutyana lomvuzo wexesha elizayo, liyanyuka njengoko umvuzo usondela. Iimpawu ezibonisa ukuba umvuzo mkhulu, usondele, okanye uqiniseke ngakumbi kunokuba bekulindelwe unobangela wokutsiba kwexabiso. Oku kutsiba ukusuka komnye umzuzu ukuya kolandelayo zii-RPE zomahluko wexeshana. e) Ukukhupha “iziseko” kungabhidanisa ixabiso kunye neempawu zeRPE. Ekhohlo, i-dopamine ilungelelaniswe ne-cue-predictive cue (ngexesha elingu-zero), ngokuthabatha okuqhelekileyo okusisiseko, kubonakala ngathi kubonisa ukuba i-dopamine itsibela kumanqanaba aphezulu xa umvuzo ungalindelwanga kangako (omdaka), ufana nomqondiso we-RPE. Ekunene, enye inkcazo yedatha efanayo, elinganisa amanqanaba e-dopamine emva Inqaku, lingabonisa endaweni yoko ukuba amanqanaba e-dopamine axhomekeke kulindelo lomvuzo (ixabiso). Uhlalutyo olongezelelweyo lufumanise ukuba umboniso wecala lasekunene usondele kwinyani (jonga iinkcukacha kwiref. ). Iphaneli a yaphinda yaveliswa, ngemvume, ukusuka kwisalathisi , Macmillan Publishers Limited….; indawo yolawulo b yaphinda yaveliswa, ngemvume, ukusuka kwisalathisi. , Elsevier; iiphaneli ziye zaveliswa kwakhona, ngemvume, ukusuka kwisalathisi , Macmillan Publishers Limited

Ukuguquguquka okukhawulezayo kwe-dopamine akubonisi nje inkuthazo, zikwaqhuba kwangoko isimilo esikhuthazayo. Iimpendulo ezinkulu zephasic zeeseli ze-dopamine zokuqalisa i-cues ukuqikelela amaxesha amafutshane okuphendula kolu lingo lunye. Ukuvuselelwa kwe-Optogenetic yeeseli ze-VTA dopamine kwenza iimpuku zikwazi ukuqala umsebenzi kumsebenzi wethu womvuzo onokwenzeka., kanye ngokungathi babelindele umvuzo ophakamileyo. Ukuvuselelwa kwe-Optogenetic ye-SNc dopamine neurons, okanye ii-axons zabo kwi-dorsal striatum, kwandisa amathuba okuhamba.,. Ngokucacileyo, ezi ziphumo zokuziphatha zibonakala kumakhulu ambalwa eemillisecond zokuqalisa kwe-optogenetic stimulation. Ukukwazi ukuxela kwangaphambili umvuzo wokunyusa inkuthazo kubonakala ngathi kulamlwa kukumodareyitha okukhawulezileyo kwe-dopaminergic yokonwaba kwe-NAc spiny neurons.. Kuba i-dopamine itshintsha ngokukhawuleza, kwaye olu tshintsho lwe-dopamine luchaphazela inkuthazo ngokukhawuleza, imisebenzi ekhuthazayo ye-dopamine ichazwa ngcono ngokukhawuleza ("phasic"), ayicothi ("tonic").

Ngaphaya koko, ukutsala isikali esahlukileyo esikhawulezayo kunye nexesha elicothayo akusombululi ingxaki ye-decoding ejongene ne-neurons ene-dopamine receptors. Ukuba i-dopamine ibonakalisa ukufundisa, ukumodareyithwa kwe-synaptic plasticity kuya kubonakala kuyimpendulo efanelekileyo yeselula. Kodwa iziphumo ezikhawulezileyo kukuziphatha okukhuthazwayo zithetha iziphumo ezikhawulezileyo ekutshixeni - umz. ngotshintsho olukhawulezayo kwimincili. I-Dopamine inokuba nazo zombini ezi ziphumo ze-postsynaptic (kunye nokunye), ke ngaba i-dopamine yoxinaniso olunikiweyo lunentsingiselo ethile? Okanye ngaba le ntsingiselo ifuna ukwakhiwa-umzekelo ngokuthelekisa amanqanaba e-dopamine ngexesha lonke, okanye ngokusebenzisa ezinye iisignali ezidibanayo ukumisela ukuba ngowuphi na umatshini weselula oza kusebenzisana nawo? Oku kunokwenzeka kuxoxwe ngakumbi ngezantsi.

Ngaba ukukhutshwa kwe-dopamine kudlulisa ulwazi olufanayo nokudubula kweeseli ze-dopamine?

Ubudlelwane phakathi kokuguquguquka okukhawulezayo kwe-dopamine kunye nexabiso lenkuthazo kubonakala kungaqhelekanga, kuba ukudubula kweeseli ze-dopamine endaweni yoko kufana ne-RPE. Ngaphaya koko, ezinye izifundo zichaze imiqondiso ye-RPE ekukhutshweni kwe-mesolimbic dopamine. Kubalulekile ukuqaphela umngeni ekutolikeni ezinye iindlela zedatha ye-neural. Iimpawu zexabiso kunye nee-RPE zihambelana enye kwenye - akumangalisi ukuba i-RPE idla ngokuchazwa njengotshintsho kwixabiso ukusuka kumzuzu omnye ukuya kwelinye ("ukwahlukana kwexeshana" RPE). Ngenxa yolu lungelelaniso kubalulekile ukusebenzisa uyilo lokulinga kunye nohlalutyo olwahlula ixabiso kwiiakhawunti zeRPE. Ingxaki idityanisiwe xa kusetyenziswa umlinganiselo we-neural oxhomekeke kwisihlobo, kunokuba uphelele, utshintsho lwesignali. Uhlalutyo lweVoltammetry luhlala luthelekisa i-dopamine ngexesha elithile lomdla kwixesha "elisisiseko" ngaphambili kulingo ngalunye (ukususa izinto zesignali ezingaxhomekekanga kwi-dopamine, kubandakanywa ukutshaja kwe-electrode kwi-voltage nganye yokutshayela kunye nokuhamba ngexesha lemizuzu). Kodwa ukususa isiseko kunokwenza uphawu lwexabiso lufane nomqondiso we-RPE. Yile nto esiyiqapheleyo kwidatha yethu yevoltammetry (Umzobo 2e). Utshintsho kulindelo lomvuzo lubonakaliswe kutshintsho kugxininiso lwe-dopamine kwangethuba kulingo ngalunye, kwaye olu tshintsho luyaphoswa ukuba umntu uthatha nje isiseko esingaguqukiyo kuzo zonke izilingo.. Izigqibo malunga nokukhutshwa kwe-dopamine kunye nekhowudi ye-RPE ke kufuneka ijongwe ngononophelo. Le ngozi yokutolikwa kwedatha ayisebenzi kuphela kwi-voltammetry, kodwa kulo naluphi na uhlalutyo oluxhomekeke kwiinguqu ezihambelanayo-ezinokuthi ziquka i-fMRI kunye ne-photometry..

Nangona kunjalo, sisafuna ukulungelelanisa ukukhutshwa kwe-dopamine enxulumene nexabiso kwi-NAc core kunye nokungabikho okungaguqukiyo kwexabiso elinxulumene ne-spiking yi-dopamine neurons., nangaphakathi kwendawo ye-VTA esecaleni ebonelela nge-dopamine kwi-NAc core. Enye into enokubakho kukuba iiseli ze-dopamine zihlala zirekhodwa kwizilwanyana ezithintelwe entloko zenza imisebenzi ye-classical conditioning, ngelixa ukukhutshwa kwe-dopamine ngokuqhelekileyo kulinganiswa kwizilwanyana ezingathintelwanga zihamba ngenkuthalo kwindawo yazo. Sicebise ukuba i-mesolimbic dopamine inokubonisa ngokuthe ngqo ixabiso "lomsebenzi" - ukuba ibonisa imfuneko yokuchitha ixesha kunye nomzamo wokufumana umvuzo. Ngokuhambelana noku, i-dopamine yonyuka ngemiqondiso eyalela intshukumo, kodwa hayi ngemiqondiso eyalela ukuthula, nokuba ibonisa umvuzo ofanayo wekamva.. Ukuba - njengakwimisebenzi emininzi yokulungisa imeko - akukho nzuzo "kumsebenzi" osebenzayo, ke utshintsho lwe-dopaminergic olubonisa ixabiso lomsebenzi lunokungabonakali kancinci.

Okubaluleke ngakumbi kunokuba yinto yokuba ukukhutshwa kwe-dopamine kunokulawulwa ekuhlaleni kwii-terminals ngokwazo, kwaye ke kubonise iipateni ze-spatio-temporal ezizimeleyo kwi-cell body spiking. Umzekelo, i-basolateral amygdala (BLA) inokuchaphazela ukukhutshwa kwe-NAc dopamine naxa i-VTA ingasebenzi.. Ngokwahlukileyo, ukungasebenzi kwe-BLA kunciphisa ukukhutshwa kwe-dopamine ye-NAc kunye nokuziphatha okukhuthazwayo okuhambelanayo, ngaphandle kokuchaphazela ukudubula kwe-VTA.. Iitheminali zeDopamine zinee-receptors zoluhlu lwee-neurotransmitters, kubandakanya i-glutamate, i-opioids, kunye ne-acetylcholine. I-Nicotinic acetylcholine receptors ivumela i-striatal cholinergic interneurons (CINs) ukulawula ngokukhawuleza ukukhutshwa kwe-dopamine.,. Nangona kudala kuphawulwa ukuba ulawulo lwasekhaya lokukhutshwa kwe-dopamine lunokubakho lubalulekile,, ayifakwanga kwiiakhawunti zokubala zomsebenzi we-dopamine. Ndicebisa ukuba ukukhutshwa kwe-dopamine dynamics ehambelana nexabiso lekhowudi livela kakhulu basekuhlaleni ulawulo, nanjengoko ukudubula kweeseli ze-dopamine kubonelela ngemiqondiso ebalulekileyo efana ne-RPE yokufunda.

I-dopamine inokuthetha njani kokubini ukufunda kunye nenkuthazo ngaphandle kokudideka?

Ngokomgaqo, umqondiso wexabiso wanele ukubonisa i-RPE ngokunjalo, kuba umahluko wexeshana we-RPEs zilutshintsho olukhawulezayo kwixabiso (Umzobo 2B). Umzekelo, iindlela ezahlukeneyo ze-intracellular kwi-neuron ekujoliswe kuzo zinokuba novakalelo ngokwahlukileyo kugxininiso olupheleleyo lwe-dopamine (ixabiso elimele) ngokuchasene notshintsho olukhawulezayo loxinzelelo (emele i-RPE). Esi sikimu sibonakala sifanelekile, xa sinikwa ukumodareyithwa kwe-dopamine entsonkothileyo ye-spiny neuron physiology kunye novelwano lwabo kwiipateni zexesha lokuxinana kwe-calcium. Ukanti oku kukwabonakala kungafuneki ngandlel’ ithile. Ukuba isibonakaliso esifana ne-RPE sele sikhona kwi-dopamine cell spiking, kufanele ukuba sikwazi ukusisebenzisa endaweni yokuphinda ufumane i-RPE kwisiginali yexabiso.

Ukusebenzisa ngokufanelekileyo i-RPE eyahlukileyo kunye neempawu zexabiso, iisekethe zabamkeli be-dopamine banokutshintsha ngokusebenzayo indlela abayitolika ngayo i-dopamine. Kukho ubungqina obunomdla bokuba i-acetylcholine inokusebenza le ndima yokutshintsha nayo. Kwangelo xesha linye njengoko iiseli ze-dopamine zivutha umlilo we-spikes ukuya kwizinto ezingalindelekanga, ii-CINs zibonisa ngokufutshane (~ 150ms) ikhefu ekudubuleni, ezingalinganiyo ngee-RPEs. Ezi khefu ze-CIN zinokuqhutywa yi-VTA GABAergic neurons kunye neeseli ezinxulumene "nokumangalisa" kwi-intralaminar thalamus, kwaye ziye zacetywa ukuba zisebenze njengomqondiso wokunxulumana nokukhuthaza ukufunda.. UMorris noBergman bacebisa ukuba ikhefu le-cholinergic lichaza iifestile zexeshana zeplastiki ye-striatal, ngexesha apho i-dopamine inokusetyenziswa njengomqondiso wokufunda. Iplastiki exhomekeke kwi-Dopamine icinezelwa ngokuqhubekayo ngeendlela ezibandakanya i-muscarinic m4 receptors kwindlela ethe ngqo ye-striatal neurons.. Iimodeli zokubonakaliswa kwe-intracellular zicebisa ukuba ngexesha lokunqumama kwe-CIN, ukungabikho kokubopha i-m4 kunokusebenza ngokubambisana kunye ne-phasic dopamine bursts ukunyusa ukusebenza kwe-PKA., ngaloo ndlela ikhuthaza utshintsho lwe-synaptic.

Iiseli ze-striatal cholinergic ke ngoko zibekwe kakuhle ukuze zitshintshe intsingiselo yomyalezo ophindaphindwayo we-dopaminergic. Ngexesha lokunqumama kwe-CIN, ukukhululeka kwebhloko ye-muscarinic ngaphezulu kwe-synaptic plasticity kuya kuvumela ukuba i-dopamine isetyenziselwe ukufunda. Ngamanye amaxesha ukukhutshwa kwiitheminali ze-dopamine kuya kuqingqwa ekuhlaleni ukuchaphazela ukusebenza okuqhubekayo kokuziphatha. Okwangoku, le ngcebiso iyaqikelelwa kwaye ayiphelelanga. Kuye kwacetywa ukuba ii-CINs zidibanise ulwazi oluvela kwiindawo ezininzi ezijikelezileyo ze-spiny neurons ukukhupha iimpawu eziluncedo zenethiwekhi ezifana ne-entropy.,. Kodwa ayicacanga kwaphela into yokuba amandla omsebenzi we-CIN angasetyenziselwa ukuvelisa imiqondiso yexabiso le-dopamine, kunye nesango leempawu zokufunda ze-dopamine.

Ngaba i-dopamine ithetha into enye kuyo yonke i-forebrain?

Njengoko umbono we-RPE ubambekile, kwakucingelwa ukuba i-dopamine yayiluphawu lwehlabathi, isasaza umyalezo wempazamo kuyo yonke i-striatal kunye ne-frontal cortical target. USchultz ugxininise ukuba iiseli zemonkey dopamine kuyo yonke i-VTA kunye ne-SNc zineempendulo ezifanayo. Uphononongo lweeseli ze-dopamine ezichongiweyo zikwafumene iimpendulo ezifana ne-RPE efana ne-RPE kwiimpuku, ubuncinci kwii-neurons ze-VTA ezisecaleni ngaphakathi kweemeko zemeko yeklasi.. Nangona kunjalo iiseli ze-dopamine ziyahluka ngokwemolekyuli kunye ne-physiologically- kwaye ngoku kukho iingxelo ezininzi ezibonisa iipatheni ezahlukeneyo zokudubula ekuziphatheni kwezilwanyana. Oku kubandakanya ukwanda kwe-phasic ekudubuleni kwimisitho echaseneyo kunye neempawu zokuqalisa engangenanga kakuhle ne-akhawunti ye-RPE eqhelekileyo. Uninzi lweeseli ze-dopamine zibonisa impendulo emfutshane-ixesha elifutshane lokuphendula kwiziganeko zeemvakalelo ezibonisa ukumangaliswa okanye "ukwazisa" ngaphezulu kwekhowudi yeRPE ethile.,. Lo mba wokulumkisa ugqame ngakumbi kwi-SNc, apho iiseli ze-dopamine ziprojekthi ngakumbi kwi-"sensorimotor" dorsal / lateral striatum (DLS,). I-subpopulations yeeseli ze-dopamine ze-SNc ziye zaxelwa ukuba zonyuka okanye ukunciphisa ukudubula ngokubambisana neentshukumo ezizenzekelayo, nangaphandle kweempawu zangaphandle.

Amaqela amaninzi asebenzisa i-fiber photometry kunye nesalathiso se-calcium ye-GCaMP ukuvavanya umsebenzi omninzi we-subpopulations ye-dopamine neurons.,. Iiseli ze-Dopamine eziprojekthi kwi-dorsal/medial striatum (DMS) zibonise umsebenzi wokudakumba okwexeshana ukuya kumothuko omfutshane ongalindelekanga, ngelixa ezo zijonge kwi-DLS zibonise ukonyuka komsebenzi.- ihambelana ngakumbi nempendulo elumkisayo. Iimpendulo ezahlukeneyo ze-dopaminergic kwiindawo ezahlukeneyo ze-forebrain zangaphambili ziye zabonwa kusetyenziswa i-GCaMP ukujonga umsebenzi we-dopamine axons kunye neeterminal.,,. Ukusebenzisa umfanekiso weefotoni ezimbini kwiigundane ezinqatshelwe entloko, uHowe noDombeck ingxelo yomsebenzi we-phasic dopamine onxulumene neentshukumo ezizenzekelayo. Oku kubonwe kakhulu kwii-axons ze-dopamine ezivela kwi-SNc eziye zaphela kwi-dorsal striatum, ngelixa i-VTA dopamine axons kwi-NAc iphendule ngakumbi ekunikezelweni komvuzo. Abanye bafumene umsebenzi onxulumene nomvuzo we-dopaminergic kwi-NAc, kunye ne-DMS endaweni yoko idityaniswe ngakumbi nezenzo ezichaseneyo. kunye nomsila ongasemva we-striatum osabelayo kwi-aversive kunye ne-novel stimuli.

Imilinganiselo ethe ngqo yokukhutshwa kwe-dopamine ikwatyhila i-heterogeneity phakathi kwemimandla engaphantsi,. Nge-microdialysis sifumene i-dopamine ukuba idityaniswe nexabiso ngokuthe ngqo kwi-NAc core kunye ne-ventral-medial front cortex, kungekhona kwezinye iindawo ezingaphakathi ze-striatum (iqokobhe le-NAc, i-DMS) okanye i-cortex yangaphambili. Oku kubangel’ umdla njengoko kubonakala ngathi kukwenza imephu kakuhle “kwiindawo eziphambili” zexabiso lekhowudi ehlala ibonwa kwizifundo zabantu ze-fMRI.,. Ngokukodwa isibonakaliso se-NAc BOLD, esinobudlelwane obusondeleyo kwisignali ye-dopamine, inyuka ngolindelo lomvuzo (ixabiso) - ngaphezulu kune-RPE.

Nokuba ezi patheni zesithuba zokukhutshwa kwe-dopamine zivela ekudubuleni okwahlukileyo kweeseli ze-dopamine, ulawulo lwasekhaya lokukhutshwa kwe-dopamine, okanye zombini, bacela umngeni umbono womyalezo we-dopamine wehlabathi. Omnye unokugqiba ukuba mininzi imisebenzi eyahlukeneyo ye-dopamine, kunye (umzekelo) ne-dopamine kwi-dorsal striatum ebonisa "intshukumo" kunye ne-dopamine kwi-ventral striatum ebonisa "umvuzo". Nangona kunjalo, ndikhetha enye indlela yokuqonda. Imimandla eyahlukeneyo ye-striatal ifumana amagalelo avela kwimimandla eyahlukeneyo ye-cortical, kwaye ke iya kube iqhuba iintlobo ezahlukeneyo zolwazi. Nangona kunjalo indawo nganye ye-striatal yabelana nge-architecture ye-microcircuit eqhelekileyo, kuquka ne-D1- ngokuchasene ne-D2- receptor ephethe i-spiny neurons., CINs, njalo njalo. Nangona kuqhelekile ukubhekisa kumacandelo ahlukeneyo e-striatal (umzekelo, i-DLS, i-DMS, i-NAc core) ngokungathi ziindawo ezicacileyo, akukho mida ebukhali ye-anatomical phakathi kwazo (iqokobhe le-NAc lihluke kancinci ngokwe-neurochemically). Endaweni yoko kukho nje i-gradients ezithambileyo kubuninzi be-receptor, ubungakanani be-interneuron njl. Ngenxa yolu yilo luqhelekileyo, ngaba singachaza umsebenzi oqhelekileyo we-dopamine, okhutshelwe kude kulwazi oluthile oluphathwayo ngummandla ngamnye?

I-striatal dopamine kunye nokwabiwa kwezixhobo ezilinganiselweyo.

Ndicebisa ukuba iintlobo ngeentlobo zeziphumo ezahlukeneyo ze-dopamine kwindlela yokuziphatha eqhubekayo zinokuqondwa njengokumodareyitha izigqibo zokwabiwa kwezibonelelo. Ngokukodwa, i-dopamine ibonelela ngoqikelelo lokuba luncedo kangakanani na ukuchitha isixhobo sangaphakathi esilinganiselweyo, kunye nesixhobo esithile esahlukileyo phakathi kwemimandla engaphantsi kwe-striatal. Kwi-"motor" striatum (~DLS) isibonelelo yintshukumo, elinganiselwe ngenxa yokuba ukuhamba kubiza amandla, kwaye ngenxa yokuba izenzo ezininzi azihambelani. Ukwandisa i-dopamine kwenza ukuba isilwanyana sithathe isigqibo sokuba kufanelekile ukuchitha amandla ukuhamba, okanye ukuhamba ngokukhawuleza,,. Qaphela ukuba umqondiso we-dopamine odibanisa "intshukumo ifanelekile" iya kuvelisa ulungelelwaniso phakathi kwe-dopamine kunye nentshukumo, nangaphandle kwe-dopamine encoding "intshukumo" ngomntu ngamnye.

Kwi-"cognitive" striatum(~DMS) izibonelelo ziinkqubo zokuqonda kuquka ingqwalaselo (esikelwe umda ngokwenkcazo) kunye nememori yokusebenza. Ngaphandle kwe-dopamine, iimpawu zangaphandle ezibonakalayo ezihlala zixhokonxa iintshukumo zoqhelaniso azihoywa, ngokungathi zijongwa njengengafanelwe kukuqwalaselwa.. Ngaphaya koko, ukuhambisa ngabom iinkqubo zolawulo lwengqiqo kuyafuneka (kuyabiza). I-Dopamine - ngakumbi kwi-DMS - idlala indima ephambili ekuthatheni isigqibo sokuba kufanelekile ukwenza lo mzamo,. Oku kunokubandakanya ukuba ngaba kuqeshwa amacebo afuna ukuqonda ngakumbi, axoxisanayo (“esekelwe kwimodeli”) yezigqibo..

Kwi-"motivational" striatum(~NAc) esinye isixhobo esisikelwe umda sinokuba lixesha lesilwanyana. I-Mesolimbic dopamine ayifuneki xa izilwanyana zenza intshukumo elula, esisigxina yokufumana umvuzo ngokukhawuleza. Kodwa iindlela ezininzi zomvuzo zinokufunyanwa kuphela ngomsebenzi omde: ulandelelwano olwandisiweyo lwezenzo ezingavuzwanga, njengokufuna ukutya. Ukukhetha ukwenza umsebenzi kuthetha ukuba kufuneka ulibale nezinye iindlela eziluncedo zokuchitha ixesha. I-mesolimbic ephezulu ye-mesolimbic dopamine ibonisa ukuba ukuzibandakanya kumsebenzi owandisiweyo okwethutyana, osebenzayo ufanelekile, kodwa njengoko i-dopamine ithotywa izilwanyana azikhathazi, kwaye endaweni yoko zinokulungiselela ukulala..

Ngaphakathi kwisekethe nganye ye-cortico-striatal loop igalelo le-dopamine kwindlela yokuziphatha eqhubekayo ke ngoko kuqoqosho (kubandakanya ulwabiwo lwezibonelelo) kunye nenkuthazo (nokuba ngaba kunjalo. luleke ukuchitha izibonelelo). Ezi sekethe azizimeleyo ngokupheleleyo, kodwa kunoko zinombutho olawulayo, ojikelezayo: iinxalenye ezininzi ze-ventral ze-striatum zinefuthe kwiiseli ze-dopamine eziprojekthi kwiindawo ezininzi ze-dorsal.,. Ngale ndlela izigqibo zokuzibandakanya emsebenzini zinokunceda ukuvuselela iintshukumo ezithile ezifunekayo, ezimfutshane. Kodwa ngokubanzi, i-dopamine ibonelela ngemiqondiso “esebenzayo”-yandisa amathuba okuba kwenziwe isigqibo-kunokuba imiqondiso “yesikhokelo” icacise. njani izibonelelo kufuneka zisetyenziswe.

Ithini indima yokubala ye-dopamine njengoko kusenziwa izigqibo?

Enye indlela yokucinga malunga nale ndima yokuvuselela ingokwemigaqo yokwenza "imida" yokwenza izigqibo. Kwiimodeli ezithile zemathematika iinkqubo zezigqibo zonyuka de zifike kwinqanaba lomqobo, xa inkqubo izibophelela kwisenzo.. I-dopamine ephezulu iya kufana nomgama osezantsi ukuya kumda, ukuze izigqibo zifikelelwe ngokukhawuleza. Le ngcamango ilula, kodwa yenza uqikelelo lobungakanani obuqinisekisiweyo. Ukunciphisa imida yentshukumo kunokubangela utshintsho oluthile kubume bexesha lokusabela, kanye oko kubonakala xa i-amphetamine ifakwe kwi-sensorimotor striatum..

Kunokuba imida emiselweyo, idata yokuziphatha kunye ne-neural ifaneleka ngcono ukuba i-threshold iyancipha ngokuhamba kwexesha, njengokungathi izigqibo ziya zingxamiseka ngakumbi. Imveliso ye-basal ganglia iye yacetywa ukuba ibonelele ngophawu olungxamisekileyo oluguqukayo, oluvuselela iindlela zokukhetha kwi-cortex.. Ukungxamiseka kwakukwakhulu xa imivuzo yexesha elizayo yayisondele ngexesha, isenza le ngcamango ifane nexabiso lekhowudi, indima esebenzayo ye-dopamine.

Ngaba indima enjalo yokuvula yanele ukuchaza iziphumo zokumodareyitha ukusebenza kwe-striatal dopamine? Oku kunxulumene nombuzo ekudala umi wokuba ngaba iisekethe ze-basal ganglia zikhetha ngokuthe ngqo phakathi kweentshukumo ezifundiweyo okanye ukhetho olukhuthazayo olwenziwe kwenye indawo,. Kukho ubuncinci iindlela ezimbini apho i-dopamine inokubonakala ngathi inempembelelo "yesikhokelo". Eyokuqala kuxa i-dopamine isebenza ngaphakathi kwendawo yobuchopho eqhuba ulwazi olukhomba ngokwendalo. Iisekethe zeBasal ganglia zinendima ebalulekileyo, esecaleni-esecaleni ejolise ekusondeleni kwimivuzo enokubakho. Iprimate caudate(~DMS) ibandakanyeka ekuqhubeni iintshukumo zamehlo ukuya kwimihlaba echaseneyo.. Umqondiso we-dopaminergic wokuba into ekwindawo echaseneyo ifanele ukujoliswa kuyo inokuba yinxalenye yolungelelwaniso phakathi komsebenzi we-dopaminergic kwi-DMS kunye neentshukumo ezichaseneyo., kunye nokuziphatha okujikelezayo okuveliswa kukukhohlisa kwe-dopamine. Impembelelo yesibini "yesalathiso" ye-dopamine ibonakala xa (kwamacala amabini) i-dopamine izilonda ezithatha iigundane zisiya kumzamo ophantsi / ukhetho olunomvuzo ophantsi, endaweni yomzamo omkhulu / iindlela ezinomvuzo ophezulu.. Oku kungabonisa inyani yokuba ezinye izigqibo zilandelana ngakumbi, kunye neempuku (kunye nabantu) ezivavanya iinketho ngexesha elinye.. Kwezi meko zesigqibo, i-dopamine isenokuhlawula indima esisiseko yokuqalisa ngokuhambisa ixabiso lokhetho olujongwayo ngoku, olunokwamkelwa okanye hayi..

Izilwanyana ezisebenzayo zenza izigqibo kumanqanaba amaninzi, rhoqo ngamaqondo aphezulu. Ngaphandle kokucinga ngezigqibo zomntu ngamnye, kunokuba luncedo ukuqwalasela umkhondo ngokubanzi ngokulandelelana kwamazwe (Ikhiwane. 1). Ngokuququzelela utshintsho ukusuka kwelinye ilizwe ukuya kwelinye, i-dopamine inokukhawulezisa ukuhamba ngeendlela ezifundiweyo.. Oku kunokunxulumana nempembelelo ebalulekileyo ye-dopamine ngexesha lokuziphatha,. Omnye umda ophambili womsebenzi wexesha elizayo kukufumana ukuqonda okunzulu malunga nokuba zivela njani iziphumo ze-dopamine kwindlela yokuziphatha eqhubekayo ngoomatshini, ngokuguqula ukusetyenzwa kolwazi ngaphakathi kweeseli enye, ii-microcircuits kunye ne-cortical-basal ganglia loops enkulu. Kwakhona, ndigxininise iindima eziqhelekileyo zokubala ze-dopamine kuluhlu lweethagethi zokubethelwa, kodwa ubukhulu becala ndingahoywanga iithagethi ze-cortical, kwaye kuya kuhlala kubonwa ukuba imisebenzi ye-dopamine kuzo zombini izakhiwo inokuchazwa ngaphakathi kwesakhelo esifanayo.

Isishwankathelo, inkcazo eyaneleyo ye-dopamine inokuchaza indlela i-dopamine enokubonisa ngayo ukufunda, kunye nenkuthazo, kwizikali zexesha elikhawulezayo, ngaphandle kokudideka. Iya kuchaza ukuba kutheni ukukhutshwa kwe-dopamine kwiithagethi eziphambili ze-covaries ezinolindelo lomvuzo nangona ukudubula kweeseli ze-dopamine akwenzi. Kwaye iya kubonelela ngeakhawunti edibeneyo yokubalekayo yezenzo ze-dopamine kuyo yonke i-striatum nakwenye indawo, echaza iziphumo ezahlukeneyo zokuziphatha kwintshukumo, ukuqonda, kunye nexesha. Ezinye iimbono ezithile ezithiwe thaca apha ziyaqikelelwa, kodwa zenzelwe ukuvuselela ingxoxo, umfuziselo, kunye nemifuniselo emitsha.

Imibulelo.

Ndiyabulela kubalingane abaninzi abanikezela ngezimvo ezinengqiqo kwidrafti yangaphambili yesicatshulwa, kubandakanya uKent Berridge, uPeter Dayan, uBrian Knutson, uJeff Beeler, uPeter Redgrave, uJohn Lisman, uJesse Goldberg, kunye noSompempe abangaziwayo. Ndiyazisola ngokuba ukulinganiselwa kwendawo kuthintele ingxoxo yezifundo ezininzi ezibalulekileyo zangaphambili. Inkxaso ebalulekileyo yanikezelwa yiNational Institute on Neurological Disorders and Stroke, National Institute of Mental Health, kunye neNational Institute on Drug Abuse.

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