IMIBUZO: Izifundo ezimbini ezibalulekileyo ezibonisa ukuba iisekethe ezahlukeneyo zikhona ukwenzela ukusetyenziswa kweswekile okunyanzelekileyo - okanye njengoko i-YBOP iyibiza, 'a indlela yokuzinkcinkca'. Bekusoloko kucingwa ukuba umlutha wokuziphatha uvela kuphela utshintsho "lweesekethe eziqhelekileyo". Ngelixa oku kusenzeka, kuyacaca ngoku ukuba 'iisekethe zokuzinkcinkca' ezahlukeneyo zikwakhona.
Oku kwenza ingqiqo yendaleko. Yindlela yokukhuthaza isilwanyana ukuba sitye kakhulu xa kukho ukutya. Ezi zijikelezo zivela kwi-hypothalamus, ekwangummandla omkhulu wokulawula ukuziphatha ngokwesondo, i-libido kunye nokwakhiwa. Andithandabuzi ukuba izilwanyana ezincancisayo 'zinazo iisekethe zokuzinkcinkca ngesondo kunye nokutya. Ukuzala yeyona nto iphambili kwimfuza yethu kwaye amathuba okukhwelana adla ngokuba mbalwa naphakathi kwamathuba okutya.
Ngokudibeneyo, ukutyeba nesifo seswekile soHlobo lwesi-2 ziphakathi kwezona ngxaki zinkulu zempilo kwisizwe sethu, kwaye ubukhulu becala ziphuma kwinto abaninzi abayibiza ngokuba “likhoboka” leswekile. Kodwa ukusombulula le ngxaki kuyinkimbinkimbi kunokusombulula umlutha weziyobisi, kuba kufuna ukunciphisa i-drive yokutya ukutya okungenampilo ngaphandle kokuchaphazela umnqweno wokutya ukutya okunempilo xa ulambile.
Kwiphepha elitsha kwi iseli, Iingcali ze-neuroscientists kwi-MIT ziye zakhupha ezi nkqubo zimbini kwiigundane kwaye zibonise ukuba ukuvimbela isiphaluka esingaziwa ngaphambili esilawula ukusetyenziswa kweswekile okunyanzelekileyo akuphazamisi ukutya okunempilo.
Umbhali ophezulu uKay Tye uthi: “Okwesihlandlo sokuqala, siye safumanisa indlela ingqondo edibanisa ngayo ukufuna iswekile enyanzelekileyo kwaye sikwabonisile ukuba ibonakala yahlukile kukutya okuqhelekileyo, okuguquguqukayo, utshilo umbhali ophezulu uKay Tye, ongumphandi kwiPicower Institute for Learning. kunye neMemori owayekhe waphuhlisa iindlela zenoveli zokufunda ukujikeleza kwengqondo kumlutha kunye noxinzelelo. "Kufuneka sifunde le sekethe nzulu ngakumbi, kodwa eyona njongo yethu kukuphuhlisa iindlela ezikhuselekileyo, ezinokuthi zithintele indlela yokutya engafanelekanga, okokuqala kwiimpuku kwaye ekugqibeleni ibe ebantwini."
Ukukhotyokiswa ziziyobisi kuchazwa njengokufuna iziyobisi okunyanzelekileyo nangona kukho iziphumo ezibi esikolweni, emsebenzini okanye ekhaya. Iziyobisi ezikhobokisayo “ziqweqwedisa” ingqondo liziko lendalo lokulungisa umvuzo, indawo ye-ventral tegmental (VTA). Kodwa ukutya ngumvuzo wendalo kwaye, ngokungafaniyo neziyobisi, kuyimfuneko ukuze uphile, ngoko akukacaci ukuba ukutya okugqithisileyo kubangelwa kukunyanzeliswa okufanayo, okanye kwenye into.
“Olu phononongo, ngokoluvo lwam, lubonisa inyathelo elibalaseleyo ekuqondeni iinkalo ezininzi ezintsonkothileyo zokuziphatha ngendlela yokondla,” utsho uAntonello Bonci, umalathisi wenzululwazi kwiZiko Lesizwe Lokusetyenziswa Kakubi Kweziyobisi, owayengabandakanyekanga kolu phando. “Nangona bekukho izifundo ezininzi ezigqwesileyo kwixa elidlulileyo, kujongwe isinyanzelo sokuphazamiseka kokusetyenziswa kweziyobisi, esi sisihlandlo sokuqala ukuba uphononongo lungene nzulu kakhulu kwaye lubanzi kwiinkalo ezifanayo zokuziphatha okunyanzelekileyo. Ngokwembono yoguqulo, indlela engaqhelekanga yokufundisa ngezinto ezininzi esetyenzisiweyo kolu phononongo ivelise ukufunyaniswa okumnandi kakhulu: ukuba ukusetyenziswa kweswekile okunyanzelekileyo kulamlwa yisekethe ye-neural eyahlukileyo kuneyomzimba, ukutya okunempilo. "
Kuphononongo, uTye kunye nomfundi wakhe ophumelele isidanga u-Edward Nieh bagxile kunxibelelwano phakathi kwe-VTA kunye ne-lateral hypothalamus (LH), elawula ukondla. Kodwa ngenxa yokuba i-LH ikwalawula iindlela ezahlukeneyo zokuziphatha kwaye iqhagamshela kwezinye iindawo ezininzi zobuchopho, akukho mntu wayekhe wahlukanisa isekethe yokondla kunye nokwenza umvuzo. U-Tye no-Nieh baqale bachonga kwaye babonakalisa nje ii-neuron ze-LH eziqhagamshela kwi-VTA kwaye barekhoda imisebenzi yabo eyenzeka ngokwendalo kwizilayi zobuchopho, ngoncedo lukaGillian Matthews, ngaphambi kokufudukela kwimifuniselo yezilwanyana. I-Electrodes irekhode umsebenzi wezi neurons ezichongiweyo ngexesha lokuziphatha kwezilwanyana.
Iimpuku ngokwendalo ziyayithanda i-sucrose - efana nabantu abathanda iisoda ezineswekile eninzi - ke uNieh waqeqesha iimpuku ukuba zifune i-sucrose kwizibuko lokuhambisa zakuva kwaye zibona umkhondo. Emva kokuba iimpuku zifunde ukuqikelela umvuzo we-sucrose kwi-cue, wabamba umvuzo malunga nesiqingatha sexesha - ukuphoxeka okukrakra. Ngamanye amaxesha, iimpuku ngokungalindelekanga zafumana umvuzo we-sucrose ngaphandle kokuxela kwangaphambili-isimangaliso esimnandi. Lo mahluko phakathi kokulindelweyo kunye namava ubizwa ngokuba yimpazamo yokuqikelela umvuzo.
Ukurekhodwa kwe-neural kubonise ukuba olunye uhlobo lwe-LH neurons oludibanisa ne-VTA lusebenze kuphela emva kokuba isilwanyana sifunde ukufuna umvuzo we-sucrose, nokuba ngaba ngokwenene wawufumene umvuzo. Enye isethi ye-LH neurons, ekufumaneni ingxelo evela kwi-VTA, ifakwe ikhowudi yokuphendula kumvuzo okanye ekushiyeni kwayo.
Emva koko, u-Nieh wasebenza kunye nomfundi we-MD / PhD kwilebhu ye-Tye, uStephen Allsop, ukuguqula iimpuku ukwenzela ukuba i-LH-VTA ye-neural projections ithwale iiprotheni ezikhanyayo ezinokuthi zisebenze okanye zithulise i-neurons kunye ne-pulses yokukhanya, indlela ebizwa ngokuba yi-optogenetics. Ukuqalisa uqikelelo kukhokelele ekutyeni okunyanzelekileyo kwe-sucrose kunye nokonyuka kokutya kakhulu kwiimpuku ezazizele. Ukungasebenzisi le ndlela kunciphise ukufuna okunyanzelekileyo kwe-sucrose okufana nokulutha, kodwa akuzange kuthintele iimpuku ezazilambile ekutyeni i-chow eqhelekileyo. UNieh uthi: “Bekumnandi oko kuba sinedatha yokurekhoda ebonisa ukuba kwenzeka njani oku kufuna iswekile kunyanzelekileyo, kwaye sinokuqhuba okanye sicinezele nje isinyanzelo sokuziphatha ngokwenza utshintsho oluchanekileyo kwisekethe ye-neural.”
"Abaphandi bomlutha baye bacinga ukuba utshintsho olusuka kwizenzo ukuya kwimikhwa ukuya ekunyanzelweni yindlela eya ekubunjweni komlutha, kodwa kanye apho kwaye kwenzeka njani oku engqondweni ibe yimfihlakalo," utsho uTye, okwanguNjingalwazi oNcedisayo woPhuhliso lwe-Whitehead Career Development. ISebe le-MIT leNgqondo kunye neNzululwazi yoLwazi. "Ngoku sinobungqina obubonisa ukuba olu tshintsho lumelwe kwisekethe ye-LH-VTA."
U-Nieh, esebenza noMatthews, i-postdoc kwi-lab ye-Tye, kwakhona wabonisa ukuba i-LH neurons ithumela umxube we-excitatory (glutamate) kunye ne-inhibitory (GABA) izibonakaliso kwi-VTA. Kodwa ngokuchasene nokulindela, yayizizibonakaliso ezithintelayo, kungekhona ezona zivuselelayo, ezibangele umsebenzi wokutyisa kwiigundane. Xa iingqikelelo ze-GABA zodwa zenziwe zasebenza, iimpuku zaziphatha ngendlela engaqhelekanga, zigragrama emazantsi ekheji kwaye zisenza intshukumo yokuzisa i-nugget yokutya emlonyeni kwaye ziyihlafune. (Babetyiswa, ngoko babengalambanga.) “Sicinga ukuba iingqikelelo ze-glutamatergic zilawula indima yoqikelelo lwe-GABAergic, isalathisa oko kufanelekileyo ukuquququda,” utshilo u-Nieh. "Omabini la macandelo kufuneka asebenze kunye ukufumana imiqondiso yokutya enentsingiselo."
"Oku kubaluleke kakhulu ebaleni, kuba le yinto ebesingayazi ngaphambili," utshilo uBonci, "kwaye inamandla okuguqula indlela esijongana ngayo nonyango lokutya kakhulu."
Abaphandi baye babonakalisa ii-neuron ze-heterogeneous ekupheleni kokufumana olu qikelelo kwi-VTA. Iseti nganye ye-LH neurons idibanisa ne-dopamine- kunye ne-GABA-evelisa i-neurons kwi-VTA. Ilebhu ngoku iphanda ukuba indlela yokondla kunye nokuziphatha kokufuna i-sucrose yahluke njani ngokusekwe kuhlobo lwe-neuron ekujoliswe kuyo.
Olu phando lwaqalwa njengenxalenye ye-2013 ye-NIH yoMlawuli omtsha we-XNUMX we-NIH, kunye nenjongo yexesha elide yokuseka i-paradigm entsha yokunyanga ukukhuluphala okungasetyenziswa kwezinye izifo ze-neuropsychiatric. Inkxaso-mali eyongezelelweyo yavela kwimithombo emininzi yoluntu kunye neyabucala, kuquka i-NSF Graduate Research Fellowship kaNieh, i-Integrative Neuronal Systems Fellowship, kunye neNkqubo yoQeqesho kwi-Neurobiology of Learning and Memory. UKara N. Presbrey, uChristopher A. Leppla, uRomy Wichmann, uRachael Neve, noCraig P. Wildes, bonke abangamalungu ePicower Institute, nabo baba negalelo kulo msebenzi.
Izazinzulu zichaze ii-neurons ezinoxanduva lokutya okugqithisileyo kwizinga elingazange libonwe ngaphambili leenkcukacha
By Anna Azvolinsky | NgoJanuwari 29, 2015
Amaqela amabini ophando azimeleyo achaze inani labantu bee-neurons kwi-hypothalamus ezinoxanduva lokuvuselela ukutya-njengomvuzo, kodwa akuyomfuneko ukuba ukhuthaze ukutya ukuze uphile. Omabini amaqela apapashe iziphumo zawo namhlanje (nge-29 kaJanuwari) ngo iseli.
"Lawa ngamaphepha amakhulu aqala ukuchaza ubunzima kunye ne-heterogeneity ye-hypothalamus kunye neeseti ezithile ze-neurons ezinokuvelisa iziphumo eziphawulekayo zokuziphatha," watsho. URalph DiLeone, i-neurobiologist kwiYunivesithi yaseYale eyayingabandakanyekanga kumsebenzi.
Ukusebenzisa i-optogenetics, i-neuroscientist UGarret Stuber kwiYunivesithi yaseNorth Carolina, eChapel Hill, kunye noogxa bakhe bafumanisa ukuba ukusebenzisa i-GABAergic neurons ngaphakathi kwe-lateral hypothalamus (LH) kukhokelele iigundane ukuba zondle rhoqo, ngelixa zivimbela umsebenzi wezi neurons zikhuthaza iimpuku ukuba zingatyi ngokugqithisileyo. Ezi neurons zahlukile kwabanye abantu be-neuronal kwi-LH eyayikade ibandakanyeka ekutyeni kunye nezinye iindlela zokuziphatha ezinxulumene nomvuzo. Xa ezi neurons zaye zacinywa ngokwemfuza, iimpuku zazingakhuthazi kangako ukufumana umvuzo wekhalori elulwelo. Oosonzululwazi baphinde babona umqondiso wekhalsiyam yamakhulu ee-GABAergic neurons ngaxeshanye kwiimpuku ezihamba simahla ngokufaka ii-microendoscopes kwi-LH kunye nokuncamathisela imakroskopu encinci ye-fluorescence kwiintloko zezilwanyana. Umfanekiso we-calcium ubonise inani elahlukileyo le-GABAergic neurons esebenzayo kwincasa yokuqala yomvuzo wokutya okanye xa iimpuku zikhupha impumlo-uphawu lomdla ekutyeni-kodwa kunqabile ngexesha lemisebenzi yomibini.
Kwi-vivo imaging calcium yenza abaphandi bafunde umsebenzi we-neuronal kwinqanaba elikhulu-kwimimandla ethile yengqondo, kusho uDiLeone. Ubuchule buphuhliswe ngu Ilabhoratri kaMark Schnitzer kwiYunivesithi yaseStanford. "Kwiminyaka emithandathu eyadlulayo, sasingenabo obu bugcisa-ukukhutshwa kwemfuza, i-optogenetics, i-vivo imaging," UPawulos Phillips, isazi ngengqondo kwiYunivesithi yaseWashington, uxelele Inzululwazi. "Kuyamangalisa ukubona ilebhu ye-Stuber idibanisa ezi zinto ngokucocekileyo ukuphendula imibuzo ebalulekileyo ye-neuroscience."
I-neurons ye-LH yahlukile, kwaye iyaziwa ngokubandakanyeka kwindlela yokuziphatha enxulumene nomvuzo njengokutya, ukusela, kunye nesondo. Kodwa ukubonakaliswa kwee-subpopulations ezahlukeneyo ze-neurons kulo mmandla wobuchopho kube ngumceli mngeni ngokwembali. “Sifumene iziphumo zokuvuselela umbane ngaphezulu kweminyaka engama-30 ngoku, kodwa besingazi [yeyiphi i-neuron] ebesiyivuselela kunye nokuba ii-neuron ezinxulumene nokondla zisuka kwi-LH okanye ezo zisandula ukudlula kude kube ziindlela ze-optogenetics. iye yafumaneka,” utshilo Roy Wise, isazi semithambo-luvo kwiZiko leSizwe lokuSetyenziswa gwenxa kweZiyobisi owayengabandakanyekanga kulo msebenzi.
"Kukho uchulumanco kwicandelo le-neuroscience kwi-imaging ye-vivo kuba ivumela, okokuqala, ukuba sifunde iipatheni zemisebenzi ngaphakathi kwee-neurons ezichazwe yi-molecularly defined subpopulations," wongezelela uStuber.
Kwisifundo sesibini, esikhokelwa yi-MIT neuroscientist Kay Tye, abaphandi bachonge abantu ababini abahlukeneyo be-neuronal kwisekethe edibanisa i-LH kunye ne-midbrain's ventral tegmental area (VTA), eyaziwayo ngomsebenzi wayo wokwenza umvuzo. Ingaba i-neurons kolu qikelelo lwe-LH-VTA iphendula iswekile ngokwayo, okanye kwisenzo sokufumana iswekile yayingaziwa, utshilo u-coauthor wokufunda. Edward Nieh, umfundi onesidanga kwilabhoratri yaseTye. Ngoku siyazi ukuba kukho iiseli zemithambo-luvo ezisabela kwiimpawu ezahlukeneyo-ukubuyisela [iswekile] kunye [neswekile] ngokwayo.
Ukusebenzisa ukuhluka kwindlela ye-optogenetics, iqela lijolise ngokukodwa kwi-neurons kwi-LH edibanisa ne-VTA. Ukuphonononga iigundane ezihamba ngokukhululekileyo, iqela lifumene ukuba i-neurons edibanisa i-LH kwi-VTA yasebenza ngexesha lokufuna umvuzo weswekile, ngaphandle kokuba umvuzo ufunyenwe. Ukuthintela le sekethi kunciphisa kuphela ukufuna iswekile okunyanzelekileyo-hayi indlela eqhelekileyo yokutya-kwezi mpuku. Ukuvuselela kuphela ii-neuron ze-GABAergic kule sekethi zivelise iindlela zokuziphatha ezingaqhelekanga: izilwanyana zaququda phantsi okanye indawo engenanto kwiikheji zazo xa kungekho kutya. Kwaye ukuvuselela ezi neurons kwakhona kubangele ukuziphatha okunyanzelekileyo kwe-classical ukoyisa isohlwayo-ukutshatyalaliswa kombane-ukufikelela kumvuzo weswekile, kunye nokunyuka kokutya okunyanzelekileyo.
“Singanciphisa ukufuna i-sucrose okunyanzelekileyo kodwa singachaphazeli ukondla kwabo okuqhelekileyo,” utshilo uNieh. "Oku kubalulekile kuba kunyango lokunyanzeliswa kokutya, sifuna kuphela ukuyeka iindawo ezingafanelekanga zokutya kwaye sigcine ukutya okuqhelekileyo."
UPhillips wathi: “Kukho ukusetyenziswa okucacileyo kokuphazamiseka kokutya yaye mhlawumbi nokusetyenziswa kakubi kweziyobisi nokungcakaza kuba isenokuba yindlela eqhelekileyo eyenza olu hlobo lokuziphatha lusebenze,” watsho uPhillips.
Kwi-imeyile eya Inzululwazi, uTye uthe ilebhu yakhe ngoku isebenzela ukuchaza ngcono isiginitsha ye-neuronal yokunqwenela enokuthi ibonwe ngexesha lokwenyani ukuphuhlisa ungenelelo lokuyeka ukutya okunyanzelekileyo kunye nezinye iindlela zokuziphatha eziluthayo ngaphambi kokuba ziqale.
JH Jennings et al., "Ukubona i-hypothalamic network dynamics for appetitive and sonsummatory behavior," iseli, doi.org/10.1016/j.cell.2014.12.026, 2015.
EH Nieh et al., "Ukucacisa iisekethe ze-neural ezilawula ukufuna i-sucrose enyanzelekileyo," Iseli, doi.org/10.1016/j.cell.2015.01.003, 2015.
;