IZIMPENDULO:
Biol Psychiatry. I-2010 Jun 15; 67 (12): 1199-204. doi: 10.1016 / j.biopsych.2009.12.029.
UDavis JF, ILoos M, I-Di Sebastiano AR, UBrown JL, Lehman MN, Coolen LM.
Umthombo
UMnyango weSeli Biology, Inyuvesi yaseCincinnati, eCincinnati, e-Ohio, e-USA.
abstract
UMLANDO:
Ukwehluleka ukuvimba ukusebenza uma sebevele bengasebenzi kahle kuyingxenye yezifo ezithile zezifo zengqondo, futhi i-medial prefrontal cortex (mPFC) ikhonjwe njengomlamuleli ongaba khona wokuvinjwa kokuziphatha. Ucwaningo lwamanje luhloliwe uma i-mPFC ibandakanyeka ekuvinjelweni kokuziphatha kobulili uma kuhlotshaniswa nemiphumela emibi.
IZINDLELA:
Kusetshenziswa amagundane abesilisa, imiphumela yezilonda zezindawo ezi-infralimbic nezangaphambi kwe-mPFC ekubonakalisweni kokuziphatha kobulili kanye nekhono lokuvimba ukunqwabelana kuhlolwe kusetshenziswa inkambiso yokuphikisana nokulinyazwa okuphikisayo.
IZIPHUMA:
Izilonda zangaphambi kwangaphambi kwecortex yamakhambi azishintshanga ukubonakaliswa kokuziphatha kocansi. Ngokuphikisana nalokhu, izilonda ze-mPFC zikuvimbe ngokuphelele ukutholakala kwezimo zokucwaswa ngocansi nezilwane ezivuselelekile ziyaqhubeka ukushada, ngokungafani nokuvinjwa kokuziphatha okuqinile kokuqondiswa kwezilwane zesilisa ze-mPFC, okuholela kuphela ku-22% yezilwane zesilisa eziqinile eziqhubeka zishade. Kodwa-ke, amagundane anezilonda ze-mPFC ayekwazi ukwakha indawo ayithandayo kunomvuzo wezocansi futhi ayenendawo yokuphikiswa kwe-lithium chloride, aphakamisa ukuthi lezi zilonda azishintshanga ukufunda okuhlanganayo noma ukuzwela kwe-lithium chloride.
IMIBUZO:
Ucwaningo lwamanje lukhombisa ukuthi izilwane ezinezilonda ze-mPFC kungenzeka zikwazi ukwakha izinhlangano ezinemiphumela ephikisayo yokuziphatha kwazo kepha zingenalo ikhono lokucindezela ukufuna umvuzo wezocansi lapho zibhekene nemiphumela ephikisayo. Le mininingwane ingaba nomthelela ekuqondeni okungcono kwesifo esivamile esingaphansi kokuphazamiseka kokulawulwa kwethonya, njengoba isimilo sokucindezela ngokocansi sinezinga eliphakeme lokudideka ngezifo zengqondo nesifo sikaParkinson.
ISINGENISO
I-medial prefrontal cortex (mPFC) ibandakanyeka emisebenzini eminingi ephakeme yohlelo lwezinzwa ezincelisayo kufaka phakathi ukulawulwa kokwenza imizwa, imizwa yokuziphatha njengokukhathazeka, kanye nokuguquguquka kokuziphatha nokwenza izinqumo (1-5). Ukwenza izinqumo okusekelwe emzuzwini kucatshangwa ukuthi kulawulwa yi-neuronal Circuit equkethe i-mPFC, amygdala, ne-striatum (6) lapho i-mPFC isebenza njengesilawuli se- “top-down” sale nqubo (7,8). Isici esiyisisekelo sokwenza izinqumo ezisekelwe emvuzweni yikhono ukulandelela ubudlelwano "bempendulo" ngokuhamba kwesikhathi (9). Ngale ndlela, lapho imiphumela ehambisana nesenzo sokuziphatha iba yimbi, imvamisa yalezi zenzo iyancipha. Lokhu kuphumela ekuvumelaniseni okuhle kokuziphatha, futhi le mpendulo incike ekusebenzeni kwe-mPFC (8, 10). Ukwehluleka kokuguqula izenzo zokuziphatha uma ziholela emiphumeleni emibi kuwuphawu oluvamile kokuphazamiseka okuhlukahlukene okuluthayo (11-15).
Izenzo zokuziphatha zocansi zabesilisa ngendondo ziyindlela yokuziphatha esekwe emvuzweni lapho ubudlelwano bempendulo buqashwa buqashelwe ukufeza inhloso yokubhalwa (16). Kodwa-ke, amagundane abesilisa ayakugwema ukwenza okulinganayo lapho ukuziphatha kobulili kubhangqwe nge-aversive stimulus lithium chloride (LiCl; 17, 18). Umsebenzi we-mPFC uhlanganiswe nokuziphatha kwabesilisa ngokobulilis (19-25) nabantu (26). Kodwa-ke, iqhaza ngqo le-mPFC ekuziphatheni kobulili lihlala lingacacile. Inhloso yocwaningo olukhona manje bekuwukuveza imiphumela yezilonda ze-mPFC ekubonakalisweni kokuziphatha kobulili, kanye nasekutholweni kokuvinjwa kokuziphatha ekuziphatheni kobulili kumagundane kusetshenziswa imodeli yokuphikisa okuhambisana nokulumbana. Izilonda zifake i-infralimbic (IL) ne-prelimbic (PL) ye-mPFC, njengoba lokhu kukhonjiswa kukhonjiswe kufinyelela ezindaweni zobuchopho ezibandakanyekile kulawulo lokuziphatha kocansi (20). Imiphumela yalolu cwaningo ikhombisa ukuthi umsebenzi we-mPFC we-intact awudingi ukubonakaliswa okujwayelekile kokuziphatha kobulili. Esikhundleni salokho, imiphumela isekela umbono wokuthi i-mPFC ilawula ukwenziwa kokuvinjwa kokuziphatha ekuziphatheni kobulili uma nje lokhu kuziphatha kuhlotshaniswa nemiphumela emibi.
IZIMPAHLA NEZINDLELA
Izilwane
Amaduna abantu abadala (i-250-260 amagundane) Amagundane weSpar Dawley atholakala kuma-lab waseHarlan (Indianapolis) afakwa egumbini elilodwa elikhanyiselwe okwenziwe ngomjikelezo okhanyiselwe emuva / umjikelezo omnyama (i-12: 12 h, izibani zivaliwe ku-10 AM) emazingeni okushisa we-72 ° F. Ukudla namanzi bekukhona ngaso sonke isikhathi. I-Ovariectomised, estrogen (sc silastic capsule with 5% 17-beta-estradiol benzoate) kanye neprogesterone (sc injing 500 μg in 0.1 ml of sesame oil) primed fem Sprague Dawley rats (210-225 gramm) used in all izivivinyo zokuvuthwa, okuyinto kwaqala amahora amane ngemuva kokuqala kwenkathi yobumnyama nokuziphatha kwenziwa ekhendeni elingunxantathu lwePlexiglas test cage (60 × 45 × 50 cm) ngaphansi kokukhanya okubomvu okukhanyayo. Zonke izinqubo zamukelwa yiKomiti Lokunakekelwa Kwezilwane kanye nokusetshenziswa kweNyuvesi yaseCincinnati, ikomidi laseNtshonalanga Ontario Animal Care Committee, futhi lahambisana nemihlahlandlela ye-NIH kanye ne-CCAC ebandakanya izilwane ezihamba ngezinyawo ocingweni.
Ukuhlinzwa kweLesion
Izilwane zazingafakwanga i-1-ml / kg umthamo (87 mg / kg Ketamine ne-13 mg / kg Xylazine). Izilwane zafakwa endaweni eyimpahla eyakhiwe ngogesi (izixhobo zeKopf, iTujunga, CA USA), kwavela isidumbu ukuze kudalulwe ugebhezi lwethu, kanti izimbobo zaziconswa ngenhla kwezindawo zokujova zisebenzisa i-dremmel drill (Dremmel, USA). I-Ibotenic acid (0.25μl, 2% ku-PBS) ifakwe ngaphakathi emhlabeni kusetshenziswa imijovo emibili ezindaweni ezihlukene zokuxhumanisa ama-dorsoventral, isikhathi ngasinye ngomzuzu we-1.5 sisebenzisa i-5μl Hamilton syringe kusixhumanisi esilandelayo esixhumene neBregma (ngesigebenga esenziwe sikhuphuke ngokuqondile): Nge-PL ne-IL izilonda: AP = 2.9, ML = 0.6, DV = −5.0 ne-−2.5. Izilonda zama-Sham zazenziwa kusetshenziswa izindlela ezifanayo, kepha kusetshenziswa imijovo yemoto (PBS). Zonke izilwane zazivunyelwe ukululama izinsuku ezingama-7-10 ngaphambi kokuhlolwa kokuziphatha.
Design
Ukuvezwa kokuziphatha kocansi
Izilonda ze-PL kanye neze-IL zenziwa ezilwaneni ezaziphathwa nge-naïve ngaphambi kokuhlinzwa. Ngemuva kokululama, izilwane zazivunyelwa ukuba zishade kanye ngesonto kuze kuboniswe ukukhipha okukodwa, amasonto amane alandelana ngemuva kokuhlinzwa. Umehluko kumingcele yezocansi (okuyi-latitude yokwenyuka, ukungena ngaphakathi, ukumiswa kwamanani, kanye nezinamba zezimali kanye nokungena) ngaphakathi kokuhlolwa ngakunye kuhlaziywa kusetshenziswa i-ANOVA yendlela eyodwa yokuhlinzwa kwe-lesion njengesici. Ukuqhathanisa kwe-post hoc kwenziwa ngokusebenzisa izivivinyo ze-Fishers PLSD, wonke amazinga we-5% abalulekile.
Ucwaningo Olukhuphukile lwe-Maze
Izilwane ezinezilonda noma zokwelashwa kwe-sham zahlolwa ku-maze ephakeme (i-EPM) ephakeme. Lokhu kuhlolwa kwenziwa emasontweni amahlanu kulandela ukuhlinzwa futhi isonto elilodwa kulandela isikhathi sokugcina sokukhwelana. I-EPM yenziwe ngaphandle kwePlexiglas ecacile futhi yayiqukethe izingalo ezine zobude obulinganayo ezisuka esikhungweni esasakha ukwakhiwa kophawu lokuhlanganisa. Izingalo zombili ze-maze zazivulekele imvelo yangaphandle kanti ezinye izingalo zombili ze-maze zaziboshwe ngogwadule obumnyama (i-40cm ukuphakama) oluleze kulo lonke ubude bengalo. Imingcele ephakathi kwendawo ephakathi nezingalo ichazwa ngemivimbo emhlophe ezingalweni ezitholakala kwi-12cm ukusuka maze phakathi. Ukuhlolwa kwe-EPM kwenziwa ngaphansi kokukhanya okufiphele, amahora we-1-4 ngemuva kokuqala kwenkathi yobumnyama. Umehluko phakathi kwezilwane ezi-sham nezelioned bezinqunywe kusetshenziswa izivivinyo ze-t zabafundi nge-5% level level.
Isimo Sokuphikisana Kobulili
Amagundane abesilisa abhekana nezigaba ezintathu zokuzalela ukuze athole isipiliyoni sobulili ngaphambi kokuhlinzwa kwe-lesion noma i-sham. Izilwane eziveze ukwanda ngesikhathi okungenani izivivinyo zokuya mating ezimbili kokukodwa kokuhlinzwa ngaphambi kokuhlinzwa zahlanganiswa kulolu cwaningo futhi zahlukaniswa ngezikhathi zamaqembu amane wokuhlola: uSham-LiCl, uLesion-LiCl, uSham-Saline, no-Lesion-Saline. Ukuhlinzwa kwe-Lesion noma i-sham kwenziwa ezinsukwini ze-3 ngemuva kweseshini lokugcina lokuqeqeshwa. Izilwane zavunyelwa ukuba zilulame isonto elilodwa ngemuva kokuhlinzwa ngaphambi kokuqala kwamaseshini wokulungisa isimo. Ngesikhathi sokuhlelwa kwemibandela, uhhafu wesilisa owesilisa onobuhlanya nowe-peed wathola i-LiCl ngemuva kokukhwelana (uSham-LiCl kanye no-Lesion-LiCl), kwathi enye ingxenye yabesilisa abahamba nge-sham ne-lesioned isebenza njengezilawuli futhi bathola usawoti ngokushesha ngemuva kokukhwelana. kanye neLesion-Saline). Ngosuku lokuma kwe-1, izilwane zazivunyelwe ukushada emjondolo owodwa futhi zalimala kungakapheli umzuzu owodwa kulandela ukuzikhipha nge-20ml / kg umthamo we-0.15M LiCl noma usawoti bese ziphinda zibuyiselwa ezindlini zazo zasekhaya. Ekuseni ngosuku lwe-2, bonke abesilisa basindwa futhi izilwane ezinosawoti zinikezwe i-20ml / kg umthamo we-0.15M LiCl, kuyilapho izilwane ezingama-LiCl ezifakwe emzimbeni zazifakwe ngomthamo ofanayo nosawoti. Le paradigm yaphindwa ngezinsuku ezingamashumi amabili zilandelana ezazinezikhathi eziyishumi zokuphimo ngokuphelele. Amapharamitha wokuziphatha kocansi aqoshwa ngesikhathi secala ngalinye. Umehluko ngamaphesenti ezilwane abonisa ama-mounts nokuvuvukala, noma ukuhlaziya kuhlaziywe kuhlolo ngalunye kusetshenziswa ukuhlaziya kwe-Chi-Square ngenqanaba lokubaluleka le-5%. Njengoba kungekho mehluko owatholakala phakathi kwamaSham-Saline namaqembu e-Lesion-Saline kunoma iyiphi ipharamitha, la maqembu amabili ahlanganiswe ukuhlaziya izibalo (n = 9) futhi aqhathaniswa neqembu leLesion-LiCl noma leqembu le-Sham-LiCl.
Okuthandwayo Kwendawo Indawo
Izilwane zezocansi ezenziwa ngocansi ziye zahlinzwa i-lesion njengoba zichaziwe ngenhla futhi zavunyelwa ukululama isonto elilodwa ngaphambi kokuhlolwa kokuziphatha. Konke ukuhlola kokuziphatha kuqale amahora we-4 ngemuva kokuqala kwenkathi yobumnyama. Imishini yokuthandela indawo ekhethiweyo yahlukaniswa ngamakamelo amathathu anegumbi lesikhungo sokungathathi hlangothi. Olunye uhlangothi lwegumbi lwalunezindonga ezimhlophe kanye nophahla lwegridi, kanti olunye uhlangothi lwalumnyama ngezinduku zensimbi ezingenasisekelo njengoba kufakwa phansi, igumbi eliphakathi nendawo limpunga ngePlexiglas flooring (iMed Associates, iSt Albans, i-VT). Okokuqala, kwenziwa isivivinyo sangaphambi kokusungulwa kokuthandwa komuntu ngamunye ngaphambi kokuqala kokulungiswa, zonke izilwane zifakwa egumbini eliphakathi nendawo ukuze zifinyeleleke kuwo wonke amakamelo imizuzu eyishumi nanhlanu futhi isikhathi sonke esachithwa egumbini ngalinye saqoshwa. Ngosuku olulandelayo, okungukuthi usuku lokubeka isimo se-1, abesilisa bashintshana ekujuleni kwenhliziyo ekhejini lakubo lapho bafakwa khona ngokushesha egumbini elingakhethwanga imizuzu engamashumi amathathu ngaphandle kokufinyelela kwamanye amagumbi noma bafakwa egumbini labo lokuqala abebelithanda imizuzu engamashumi amathathu ngaphandle kokuziphatha kocansi kwangaphambilini. Ngosuku lwesibili lokunakekelwa kwezimo, abesilisa bathola impatho ehlukile. Le paradigm yesimo iphindwe futhi. Ngosuku olulandelayo, kwenziwa ukuhlolwa okwenziwa ngemuva kwalokho kwafana ncamashi nokuhlolwa kwangaphambi kokuhlolwa. Kusetshenziswe amanani amabili ahlukene ukuthola ukuthi izilwane ezi-mPFC eziklanyelwayo zakha indawo ekhethiweyo yokuthanda ucansi. Amaphuzu okuqala kwaba amaphuzu umahluko, achazwa njengomehluko phakathi nesikhathi esichithwe egumbini elithandwa ekuqaleni nesikhathi esichithwa egumbini lokuqala elingathandwanga. Isibalo sokuthandwayo sachazwa njengesikhathi esisetshenziselwe igumbi lokuqala elingakhethwanga lihlukaniswe yisikhathi esisetshenziselwe igumbi lasekuqaleni elingathandiswanga kanye nesikhathi esichithwe kwigumbi lokuqala lalincamela. Izikolo ezikhethwayo nokwehluka ziye zaqhathaniswa esilwaneni ngasinye phakathi kokuhlolwa kwangaphambi kokuhlolwa kokufika neposi kusetshenziswa izivivinyo ze-t-test zabafundi ngababili ngamazinga wokubaluleka we-5%. Ucwaningo lwangaphambilini luveze ukuthi ukuvuthwa kwemiphumela kuholela ekuthandweni kwendawo enomdlandla usebenzisa le paradigm, nokuthi ukwelashwa okulawulayo akuholeli kuguquko ekuthandweni (27-29).
Isiphambeko sendawo Ehluliwe
Izilwane ezenziwa ngocansi nge-naïve ziye zahlinzwa i-lesion noma i-sham njengoba zichaziwe ngenhla futhi zavunyelwa ukuba zilulame isonto elilodwa ngaphambi kokuhlolwa kokuziphatha. Konke ukuhlola kokuziphatha kuqale amahora we-4 ngemuva kokuqala kwesikhathi sokukhanya. Besebenzisa izinsiza kusebenza ze-CPP ezichazwe ngenhla, imijovo ye-LiCl noma ye-saline yahlanganiswa ngegumbi lokuqala elithandwayo noma elingathandanga ngokulandelana ngesikhathi sokulingwa okubili kokulinganisa ngendlela elinganiselayo. Kwenziwa izivivinyo zangaphambi nangemva kwalokho kwahlaziywa imininingwane njengoba kuchaziwe ngenhla kusetshenziswa izivivinyo ze-t zabafundi ezinamazinga we-5%.
Ukuqinisekiswa kweLesion
Okwezilwane zokuqinisekiswa kwe-lesion zenziwa kahle ngamakhambi nge-4% paraformaldehyde kwathi ubuchopho babekwa eceleni (coronally). Izingxenye zazivinjelwe ukumakwa kwe-neuronal NeuN isebenzisa i-antiserum eyinhloko kusisombululo sokufakwa ekufukameleni eqaphela i-NeuN (monoclonal anti-NeuN antiserum; 1: 10,000; Chemicon) nezindlela ezijwayelekile ze-immunoperoxidase (19). Indawo nosayizi wezilonda ze-ibotenic kunqunywe ngokuhlaziya indawo ezingxenyeni eziseceleni ze-mPFC ezingenayo i-NeuN neuron stain. Izilonda ze-mPFC zivame ukuskena ibanga ukusuka ku-AP + 4.85 kuye ku- + 1.70 okuhlobene ne-bregma (Umfanekiso 1A-C). Izilonda zithathwe njengeziphelele uma i-100% ye-IL ne-80% ye-PL ibhujisiwe, futhi yizilwane kuphela ezinezilonda eziphelele ezifakiwe ekuhlaziyweni kwezibalo (Ukuhlolwa kobuntu bokuziphatha kobulili, i-lesion n = 11, sham n = 12; ukuhlolwa kwe-EPM, i-lesion n = 5, sham n = 4; isilingo se-sex shaversion, i-sham-saline n = 4, i-sham-LiCl n = 9, i-lesion-saline n = 5, i-lesion-LiCl n = 12; ; Ukuhlolwa kwenkundla yokuhlola indawo, sham n = 5, lesion n = 12).
IZIPHUMA
Ukuziphatha ngokocansi
Izilonda ze-PL / IL azikhange zithinte noma isiphi isitho sokuya ocansini esivivinyiwe kwabesilisa ababekade behlukunyezwa ngokocansi ngaphambi kokuhlinzwa (Umdwebo 1D-F). Esivumelwaneni, akukho miphumela yezilonda ze-PL / IL zokuziphatha kobulili ezitholakele kwabesilisa abanolwazi lwezocansi olufakiwe ocwaningweni lokuvukela ubulili obunemizwa, ngesikhathi sokuqulwa kwecala lokuqala, yingakho ngaphambi kokubhanqa iLiCl ngokuziphatha kocansi (Ithebula 1). Ngakho-ke, izilonda ze-PL / IL azizange zithinte ukusebenza kwezocansi ngaphandle kokuhlangenwe nakho kocansi.
I-Maze ephakanyisiwe
Ngokuvumelana nemibiko yangaphambilini (27-29), amagundane abesilisa abanezilonda ze-mPFC abonise okufakiwe okuningi ezingalweni ezivulekile ze-EPM ngokuqhathaniswa nezilawuli (Umfanekiso 1G), okuphakamisa ukuthi umsebenzi we-mPFC ubalulekile ezimweni ezidinga ukuhlolwa kobungozi.
Ukugwema ukuya ocansini okunesimo
Imiphumela yokuma kwesimo se-LiCl ngokuziphatha kocansi
Ukulungiswa kwe-LiCl kuholele ekunciphiseni okukhulu kwamaphesenti wesilisa ama-sham abonisa ama-mounts, ukungena ngaphakathi, noma ukujuluka kwemvelo kuqhathaniswa nokulawulwa kwe-sham saline (Umdwebo 2A-B). Kodwa-ke, izilonda ze-mPFC zivimbele ngokuphelele ukuthintela okubangelwa isimo seLiCl. Ukuhlaziywa kwe-Chi-mraba kuveze umehluko omkhulu phakathi kwamaqembu atholakele ngamaphesenti ezilwane abonisa izindunduma (Umfanekiso 2A), ukungena ngaphakathi (akubonisiwe; idatha efana ne- Umfanekiso 2A), noma ukukhipha (Umfanekiso we-2B). Ngokukhethekile, amaphesenti abesilisa abonisa ama-mounts, ama-intromissions, noma ama-ejacation ayephansi kakhulu eqenjini le-Sham-LiCl uma kuqhathaniswa nezilwane ezilawulwa yi-Saline (i-Sham ne-Lesion), okubonisa umphumela ophazamisayo wokuma kwe-LiCl ekuphatheni ezilwaneni ze-Sham. Ngokuphambene, awukho umphumela wesimo seLiCl owabonwa kwabesilisa bakwaLesion-LiCl (Amanani 2A-B). Ngakho-ke, umsebenzi we-mPFC ubalulekile ekutholakaweni kokuvinjezelwa okunesimo kokuziphatha kobulili. Kodwa-ke, kungenzeka ukuthi izilonda ze-PL / IL zibambe ukuhlangana okuhambisana nomvuzo wokuya ocansini, ngenxa yalokho emiphumeleni ehlukile yokufunda yezilonda ze-PL / IL zokutholwa kwendawo enekhethelo yomvuzo wezocansi ihlolwe.
Ukuthanda Indawo Okuthandwayo Nokuphikiswa
Amagundane anezilonda ze-mPFC abonise ukufundwa okujwayelekile kokuhlangana kwezinkomba zokuqukethwe okuhambisana nomvuzo wokuya ocansini, njengoba kuboniswa wukukhuphuka kwenqaku lesilinganiso kanye nenqaku lokuthandwa ngesikhathi sokuhlolwa kwamuva (Umdwebo 3A-B). Ngaphezu kwalokho, izilonda azizange zithinte ukufunda okuhambisana nokuhlangana kokuqukethwe ne-LiCl eyenziwe ngeLiCl, kuboniswe ukwehla okukhulu komehluko kanye nezikolo ezikhethiwe ngesikhathi sokuhlolwa kweposi (Umdwebo 3C-D).
UKUKHULUMA
Kulolu cwaningo, sibika ukuthi izilonda zezifunda ze-IL ne-PL ze-mPFC azithinti ukubonakaliswa kokuziphatha kobulili, noma ukutholwa kwendawo enombandela okuthandayo kunomvuzo wezocansi. Esikhundleni salokho, izilonda zivimbela ukutholwa kocansi olunezimpikiswano. Le miphumela inikezela ngobufakazi obusebenzayo be-hypothesis yokuthi amandla okwenza izinguquko zokuziphatha eziguqukayo zilawulwa yi-IL kanye ne-PL subregions ye-mPFC.
Idatha yangaphambili evela elabhorethri yethu iveze ukuthi ama-mPFC neurons ayasebenza ngesikhathi sokuziphatha kocansi kumagundane abesilisa (20). Kodwa-ke, ama-mPFC akhishwe amagundane kulolu cwaningo awahlukaniseki kumagundane okulawulwa kwe-sham kunoma yikuphi ukubonwa okuhlaziywa kokuziphatha kocansi. Ngokuvumelana nemibiko yangaphambilini (30, 32) Izilonda ze-mPFC zikhiqize imiphumela ekhathazayo njengoba ihlolwe ukusebenza kumaza ophakeme futhi, okukhombisa ukuthi umthetho olandelwayo wethu uyasebenza. Ngakho-ke, imiphumela yamanje iphakamisa ukwenziwa kwe-IL ne-PL ukwahlukaniswa kwe-mPFC ngesikhathi sokuziphatha kocansi akudingekile ekubonisweni okujwayelekile kokuziphatha kocansi. Ngokuphambene nalokho, ucwaningo lwangaphambilini olwenziwe ngu-Agmo nabantu osebenza nabo luveze ukuthi izilonda zendawo engaphandle kwe-cingate (ACA) zanda ngokwenyuka nokuphuma kokungena futhi zanciphisa iphesenti labesilisa elalingisa (25). Ngakho-ke, kungenzeka ukuthi i-ACA ibambe iqhaza ekusebenzeni kokuziphatha kobulili, kanti izifunda ze-IL nezingu-PL zivumelana ekuvinjelweni kokuziphatha okokuhambisana nemiphumela emibi.
Yize izilonda ze-mPFC kubikwe ukuthi ziphazamisa izindlela ezahlukahlukene zokuqiniswa kwememori (33, 34), imiphumela yezilonda ze-mPFC ekuvinjelweni kokuziphatha okubikwe lapha ayinakubalwa ekushoneni kokufunda. Ehlelweni elihlukile lokuhlola abesilisa abakhokhelwa abakwa-MPFC bahlolwe ikhono lokuthola indawo ekhethiwe yokuthanda ukuzibandakanya ocansini. Isifundo esihlobene nomvuzo sihlala singeneme ezilwaneni ezithuthukisiwe ze-mPFC njengoba laba besilisa bekwazi ukwakha indawo ethokomele yegumbi elibhangqiwe lomvuzo wezocansi. Lokhu okutholakele kuvumelana nezifundo ezedlule ezihlola iqhaza le-PL noma i-mPFC ephelele yokutholwa kwe-psychostimulant indosed CPP (35, 36), Ngaphezu kwalokho, ukufunda okuhambisana nesisusa sokuvuselela amandla i-LiCl akuzange kuthintwe yizilonda ze-mPFC, kuyahambisana nemibiko yangaphambilini yokuthi imiphini ye-PFC ayikuvimbanga ukutholwa kokuphambanisa ukunambitheka okunombandela (34). Ngokubanzi le datha iphakamisa ukuthi ukwenziwa kokuqala kokusebenza kokuhlukaniswa kwe-PL / IL ngaphakathi kwe-mPFC (20) azidingekile ekutholakaleni kwemfundo ehambisana nomvuzo, kepha ziyadingeka ukuze lusetshenziswe kahle lolu lwazi njengoba luhlobene nokuphathwa kokulawulwa kokuziphatha. Lo mbono uvumelana nengxabano ekhona yamanje yokuthi umsebenzi we-IL uyadingeka ukuze ucubungule futhi usebenze ngokufakwayo kokuvinjezelayo kanye nokujabulisayo okudlulisela imininingwane mayelana nezikhathi zokubuyisa umvuzo (37). Ngaphezu kwalokho, izilwane ezine-PL (35) noma IL (8, 37, 38) izilonda zibonisa ukufunda okujwayelekile kokuqothuka yize kungakwazi ukusebenzisa lolu lwazi ukwenza izinqumo eziqondiswe kumgomo.
Sengiphetha, ucwaningo lwamanje lukhombisa ukuthi izilwane ezinezilonda ze-mPFC kungenzeka zikwazi ukwakha izinhlangano ngemiphumela engemihle yokuziphatha kwazo, kepha zingenakho ukucindezela kokufuna ukuthola umvuzo wezocansi uma zibhekene nemiphumela emibi. Kubantu ukuvuswa kocansi kungukuhlangenwe nakho okuyinkimbinkimbi lapho ukucubungulwa kolwazi lokuqonda okungokomzwelo kusebenza khona ukunquma ukuthi ngabe izakhiwo ze-hedonic zesikhuthazi esithile zanele ukusebenza njengento yokuvuselela ezocansi (39). Idatha yamanje iphakamisa ukuthi ukungasebenzi kahle kwe-mPFC kungahle kube nomthelela ekuthatheni ubungozi bezocansi noma ekufuneni ngenkani indlela yokuziphatha kwezocansi.
Ngaphezu kwalokho, ukungasebenzi kahle kwe-mPFC kuhlotshaniswe nokuphazamiseka kwengqondo okuningana (13, 40) ephakamisa ukuthi ukungasebenzi kwe-mPFC kungaba yindlela eyisisekelo esetshenziswana nobunye ubucakacaka futhi nokuthi ukuziphatha okuya ocansini okuphoqayo kungahlotshaniswa nokunye ukuphazamiseka. Ngempela, kubantu, i-hypersexuality noma ukuziphatha okuphathelene nocansi kuye kwabikwa ukuthi kunamazinga aphezulu we-comorbidity enezimo zengqondo (kufaka phakathi ukusetshenziswa kabi kwezidakamizwa, ukukhathazeka, nokuphazamiseka kwemizwa) (41), kanye ne-pafupifupi10% yokwanda kwesifo seParkinson's pamwe nokuthenga okuphoqayo, ukugembula, nokudla (42-44).
Imibhalo yaphansi
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