COMMENTSIzifundo ezimbili eziyingqophamlando ezibonisa ukuthi kukhona amasekethe ahlukene okusetshenziswa ngocansi okuphoqelela - noma njengoba i-YBOP ikubiza kanjalo, 'a umshini wokuluma'. Bekulokhu kucatshangwa ukuthi imilutha yokuziphatha ivela kuphela ukuguqulwa "kwemijikelezo ejwayelekile". Ngenkathi lokhu kwenzeka, manje sekuyabonakala ukuthi 'amasekethi wokuzitika' ahlukile nawo akhona.
Lokhu kwenza umqondo wokuziphendukela kwemvelo. Kuyindlela yokunxusa isilwane ukuthi sidle ngokweqile lapho ukudla kutholakala. Le mibuthano ivela ku-hypothalamus, okuyisifunda esikhulu sokulawula sokuziphatha ngokocansi, i-libido kanye nama-erections. Anginakungabaza ukuthi izilwane ezincelisayo zisebenzisa 'imijikelezo yokuzitika' ngocansi kanye nokudla. Ukuzala kuyinto ebaluleke kakhulu yezakhi zofuzo kanye namathuba okukhwelana ngokuvamile abe mbalwa futhi aqhelelene kunamathuba okudla.
Ngokubambisana, ukukhuluphala kanye nohlobo lweShukela 2 sikashukela phakathi kwezinkinga ezinkulu zezempilo ezweni lethu, futhi ngokuyinhloko zivela kulokho abaningi abakubiza ngokuthi “umlutha” ushukela. Kepha ukuxazulula le nkinga kuyinkimbinkimbi kakhulu kunokuxazulula ukuxazulula izidakamizwa, ngoba kudinga ukunciphisa idrayivu ukudla ukudla okungenampilo ngaphandle kokuthinta isifiso sokudla ukudla okunempilo lapho ulambile.
Kwiphepha elisha ku Iseli, ama-neuroscientists e-MIT azithululile lezi zinqubo ezimbili kumagundane futhi akhombisa ukuthi ukuvimba umjikelezo wobuchopho obekade ungaziwa olawula ukusetshenziswa okuphoqelekile kokusebenzisa ushukela akukuphazamisi ekudleni okunempilo.
"Ngokokuqala ngqa, sikhombe ukuthi ubuchopho buhlanganisa kanjani ukufuna ushukela futhi sikhombisile nokuthi kubonakala sengathi kuhlukile ekudleni okujwayelekile nokuvumelanayo," kusho umlobi omkhulu uKay Tye, umphenyi wemigomo ePicower Institute for Learning kanye neMemory eyake yathuthukisa amasu enoveli wokufunda ukujikeleza kobuchopho kumlutha nokukhathazeka. "Sidinga ukufundisisa kabanzi lo mbuthano, kepha inhloso yethu enkulu ukuthuthukisa izindlela eziphephile ezingavikeleki zokugwema izindlela zokudla ezingahambanga kahle, okokuqala kumagundane bese kuthi ekugcineni kubantu."
Ukuluthwa yizidakamizwa kuchazwa njengokufuna izidakamizwa ngenkani yize kunemiphumela emibi esikoleni, emsebenzini, noma ekhaya. Izidakamizwa eziyimilutha “ziyaduna” ubuchopho buyisikhungo semvelo sokucubungula umvuzo, indawo ye-ventral tegmental (VTA). Kepha ukudla kungumvuzo wemvelo futhi, ngokungafani nomuthi, kuyadingeka ukuze usinde, ngakho-ke bekungakacaci ukuthi ngabe ukudla ngokweqile kusuka empoqweni ofanayo, noma kokunye okuthile.
"Lolu cwaningo lumele umbono wami isinyathelo esivelele ekuqondeni izici eziyinkimbinkimbi zokuziphatha kahle," kusho u-Antonello Bonci, umqondisi wesayensi eNational Institute on Drug Abuse, obengabandakanyekanga ocwaningweni. “Ngenkathi kube nezifundo eziningi ezinhle kakhulu esikhathini esidlule, sibheka ukuthi ngabe yiphi inkinga yokuphazamiseka kokusebenzisa izidakamizwa, lesi okokuqala ngqa ukuthi isifundo singene shí kakhulu nangokuphelele ezicini ezifanayo zokuziphatha okuyimpoqo kokudla. Ngokombono wokuhumusha, indlela eyingqayizivele yezizwe eziningi esetshenziswe kulolu cwaningo iveze ukuthokozisa okujabulisayo: ukuthi ukusetshenziswa kwenshukela okuphoqayo kuqondiswa yisekethe ehlukile ye-neural kunokudla ngokomzimba, okunempilo. ”
Kulolu cwaningo, uTye kanye nomfundi wakhe ophothule u-Edward Nieh bagxila ekuxhumaneni phakathi kwe-VTA ne-lateral hypothalamus (LH), elawula ukondla. Kepha ngoba i-LH futhi ilawula ezinye izindlela ezihlukile zokuziphatha futhi ixhumeka kwezinye izindawo eziningi zobuchopho, akekho noyedwa owayesehlukanise umjikelezo wokudla nowokuvuza. UTye noNieh baqale bakhomba futhi babonakala njengama-neurons we-LH axhuma kwi-VTA futhi baqopha imisebenzi yabo yemvelo ezinsikeni zobuchopho, ngosizo lukaGillian Matthews, ngaphambi kokuya ezivivinyweni zezilwane. Ama-Electrodes aqopha umsebenzi walezi zinzwa ezihlonziwe ngesikhathi sokuziphatha kwezilwane.
Amagundane ngokwemvelo athanda i-sucrose - afana nabantu abathanda ama-sodas acebile ngoshukela - ngakho-ke uNieh waqeqesha amagundane ukufuna i-sucrose ethekwini lokulethwa lapho ezwa futhi ebona inkomba. Ngemuva kokuthi amagundane afunde ukubikezela umvuzo we-sucrose ngemuva kokuthola okuthile, wavele wagodla umvuzo cishe isigamu sesikhathi - ukuphoxeka okubuhlungu. Ngezinye izikhathi, amagundane athola umklomelo we-sucrose ngokungalindelekile ngaphandle kokuthola inkomba yokubikezela - isimanga esihle. Lo mehluko phakathi kokulindelwe nesipiliyoni ubizwa ngokuthi iphutha lokubikezela umvuzo.
Ukuqoshwa kwe-neural kukhombisa ukuthi uhlobo olulodwa lwe-LH neurons exhuma ku-VTA lwasebenza kuphela ngemuva kokuthi isilwane sifunde ukufuna umvuzo we-sucrose, noma ngabe siwutholile noma cha. Enye isethi yama-LH neurons, ngemuva kokuthola impendulo evela ku-VTA, ifake ikhodi impendulo kumvuzo noma kokusalayo.
Ngokulandelayo, uNieh wasebenza nomfundi we-MD / PhD ebhodini likaTye, uStephen Allsop, ukuguqula amagundane ukuze ukuqagela kwe-LH-VTA neural kuthwale amaprotheni azwela ukukhanya angavula noma athule ama-neurons ngokukhanya kokukhanya, indlela ebizwa nge-optogenetics. Ukwenza kusebenze ukuqagela kuholele ekuphoqeleni ukudla i-sucrose kanye nokwanda kokudla ngokweqile kumagundane abesegcwele. Ukwenza kungasebenzi le ndlela kunciphise ukufuna okungafuneki kwe-sucrose okufana nokulutha, kepha akuvimbanga amagundane ayelambile ekudleni i-chow ejwayelekile. "Lokho bekujabulisa ngoba sinemininingwane yokurekhoda ukukhombisa ukuthi kwenzeka kanjani lokhu kufunwa ngoshukela okuphoqelekile," kusho uNieh, "futhi singakwazi ukushayela noma ukucindezela ukuziphatha okucindezelayo ngokwenza izinguquko ezinembe kakhulu esifundeni se-neural."
"Abaphenyi bezidakamizwa baye bacabanga ukuthi ukushintsha kusuka ezenzweni kuya emikhubeni yokuphoqelela kuyindlela yokwakheka kwezidakamizwa, kodwa ukuthi lokhu kwenzeka kuphi futhi kanjani ebuchosheni kuye kwaba yimfihlakalo," kusho uTye, obuye abe ngu-Whitehead Career Development Assistant Professor UMnyango Wezobuchopho Nezokucwaninga we-MIT. "Manje sinobufakazi obukhombisa ukuthi lolu shintsho lumelwe esifundeni se-LH-VTA."
UNieh, esebenza noMatthews, i-postdoc ebhodini leTye, uphinde wakhombisa ukuthi ama-LH neurons athumela ukuxubana kwesiginali ye-excitatory (glutamate) ne-inhibitory (GABA) ku-VTA. Kepha ngokungafani nokulindelwe, bekuyizimpawu zokuvimbela, hhayi lezo ezijabulisayo, ezenze umsebenzi wokudla kumagundane. Ngenkathi kuvulwa ukuqagela kwe-GABA kukodwa, amagundane aziphethe ngendlela exakile, ehla enyuka ekhejini futhi efaka izinhloso zokuletha isilondolozi sokudla emlonyeni nokuhlafuna. (Babephiwe ukudla, ngakho-ke babengalambile.) “Sicabanga ukuthi ukuqagela kwe-glutamatergic kulawula indima ye-GABAergic projektha, kuqondise ukuthi yini efanelekile ukuziluma,” kusho uNieh. "Zombili lezi zinto kufanele zisebenzisane ukuze zithole izimpawu zokudla ezizuzisayo."
"Lokhu kubaluleke kakhulu emkhakheni, ngoba le yinto ebesingayazi ngaphambili," kusho uBonci, "futhi inamandla okuguqula indlela esisebenzisa ngayo ukwelashwa ngenxa yokudla ngokweqile."
Abaphenyi baphinde babonakalise ama-neurons asezingeni eliphakeme ekutholeni kokuqhamukwa kwalokhu ku-VTA. I-subset ngayinye ye-LH neurons ixhumeka ngama-dopamine- kanye nama-neuron akhiqiza i-GABA ku-VTA. I-lab manje isiphenya ukuthi izindlela zokudla nezokufuna ukuzibamba zihluka kanjani ngokuya ngohlobo lwe-neuron oluqondiwe.
Lokhu kucwaninga kwaqalwa njengengxenye yeTye's 2013 NIH Director's New Investigator Award, ngenhloso yesikhathi eside yokusungula ipharadigm entsha yokwelapha ukukhuluphala engasetshenziswa nakwezinye izifo ze-neuropsychiatric. Imali eyengeziwe yavela emithonjeni eminingi yangasese yomphakathi neyangasese, kufaka phakathi iNieh's NSF Graduate Research Fellowship, I-Integrative Neuronal Systems Fellowship, kanye noHlelo Lokuqeqeshwa ku-Neurobiology of Learning and Memory. UKara N. Presbrey, uChristopher A. Leppla, uRomy Wichmann, uRachael Neve, noCraig P. Wildes, wonke amalungu e-Picower Institute, nabo baba negalelo kulo msebenzi.
Ososayensi bachaze ama-neurons abhekele ukusetshenziswa ngokweqile kokudla ngezinga lemininingwane engakaze ibonwe
By Anna Azvolinsky | Janawari 29, 2015
Amaqembu amabili ocwaningo azimele achaze inani lama-neurons ku-hypothalamus ebhekele ukuvuselelwa komvuzo, kodwa ngokungenasidingo ukuthi idle ukudla ukuze usinde. Womabili la maqembu ashicilele abakutholile namuhla (Januwari 29) in Iseli.
"Lawa ngamaphepha amakhulu aqala ukuchaza ubunzima kanye ne-heterogeneity ye [hypothalamus] kanye nesethi ethile yama-neurons engakhiqiza imiphumela emangalisayo yokuziphatha," kusho I-Ralph DiLeone, udokotela oyi-neurobiologist eYale University owayengahlanganyeli kulo msebenzi.
Isebenzisa optogenetics, neuroscientist Garret Stuber eNyuvesi yaseNorth Carolina, eChapel Hill, kanye nozakwabo bathola ukuthi ukusebenza kwe-GABAergic neurons ngaphakathi kwe-lateral hypothalamus (LH) kuholele ukuthi amagundane ondle kaningi, ngenkathi kuvimbela umsebenzi walezi zinzwa kwakhuthaza amagundane ukuthi angadli ngokweqile. La ma-neurons ayehlukile kwezinye izakhi ze-neuronal ku-LH ngaphambili ezazifakwe ekudleni nakwezinye izindlela ezihlobene nomvuzo. Lapho la ma-neuron ephuculwa izakhi zofuzo, amagundane awashukunyiselwa ukuthola umvuzo wekhalori owuketshezi. Ososayensi baphinde babona i-calcium signing yamakhulu e-GABAergic neurons ngasikhathi sinye emahhashini ahamba ngokukhululeka ngokufaka ama-microendoscopes ku-LH futhi ifake i-microscope ye-miniaturized fluorescence emakhanda ezilwane. Ukuqagela kwe-calcium kukhombisa inani elihlukile lama-Gabaergic neurons asebenzayo ekunambelweni kokuqala komvuzo wokudla noma lapho amagundane ekhala emakhaleni abo - okuwuphawu lokuthanda ukudla — kepha akuvamile phakathi nayo yomibili imisebenzi.
Ukuqagela i-vivo calcium imaging kwenza abacwaningi bakwazi ukufunda imisebenzi ye-neuronal ngezinga elikhudlwana — ezifundeni ezithile zobuchopho, kusho uDiLeone. Le ndlela yasungulwa ngu UMark Schnitzer's Laborator's eStanford University. "Eminyakeni eyisithupha edlule, besingenabo lobu buchwepheshe — ukufuthwa ngofuzo, optogenetics, emcabangweni we-vivo," Paul Phillips, isazi sezinzwa e-University of Washington, sitshele Usosayensi. "Kuyamangaza ukubona ilebhu yaseStuber ihlanganisa ihlanzekile ukuze iphendule imibuzo ebalulekile ye-neuroscience."
Ama-neurons we-LH ahlukahlukene, futhi ayaziwa ukuthi azibandakanye ekuziphatheni okuhlobene nomvuzo njengokudla, ukuphuza kanye nezocansi. Kepha ukubonakala kokuhlukahluka okungafani kwama-neuron kule ndawo yobuchopho bekulokhu kuyinselele ngokomlando. "Sibe nokutholwa kokunyusa kagesi isikhathi esingaphezu kweminyaka ye-30 manje, kodwa besingazi [ukuthi yimaphi ama-neurons] esasikhuthaza nokuthi ngabe ama-neurons ahlobene nokudla avela kwi-LH noma lawo asedlula kuze kube amasu we-optogenetics satholakala, ”kusho URoy Wise, isazi sezinzwa e-National Institute on Drug Abuse owayengahlanganyeli kulo msebenzi.
"Kukhona injabulo emkhakheni we-neuroscience we-imaging ye-vivo ngoba kusivumela, okokuqala, ukutadisha amaphethini wokusebenza kokukhiqizwa kwamangqamuzana achazwe ngama-neurons," kungeza uStuber.
Esifundweni sesibili, eholwa yi-MIT neuroscientist Kay Tye, Abaphenyi bathole abantu ababili abahlukene be-neuronal esifundeni esixhuma i-LH nendawo ye-midbrain's ventral tegmental (VTA), eyaziwa ngomsebenzi wayo wokucubungula umvuzo. Ukuthi ama-neurons kulezi projekthi ze-LH-VTA aphendula ushukela uqobo, noma isenzo sokuthola ushukela bekungaziwa, kusho ucwaningo coauthor U-Edward Nieh, umfundi othweswe iziqu elabhorethri likaTye. “Manje sesiyazi ukuthi kunokuqhamuka kwama-neurons aphendula izindlela ezahlukahlukene — ukubuyisa [ushukela] kanye [noshukela] uqobo.”
Kusebenzisa ukuhlukahluka kwinqubo ye-optogenetics, iqembu laliqondise kuphela ama-neurons ku-LH axhumanisa ne-VTA. Kuhlolisisa amagundane ahamba ngokukhululeka, iqembu lithole ukuthi ama-neurons axhumanisa i-LH ku-VTA asebenze lapho kunesenzo sokufuna umvuzo kashukela, ngaphandle kokuthi umvuzo uwutholile. Ukuvimbela lo mbuthano kunciphise kuphela ukufuna okucindezelayo kokufuna ushukela — hhayi okuvamile — kulezi zintwala. Ukunyakazisa ama-neurons we-GABAergic kuphela kule sekethe kwaveza isimilo esingajwayelekile: izilwane ziququde phansi noma isikhala esingenalutho emakhejini abo lapho kungekho kudla. Futhi ukuvuselela la ma-neurons nakho kuholele ekuziphatheni okucindezelayo okuvela ekuqaleni kokunqoba isijeziso — ukushaqeka kukagesi — ukuthola umvuzo kashukela, nokwanda ngokweqile kokudla ngokweqile.
"Singakunciphisa ukufuna ukuphoqelela okuphathelene nocingo kodwa singakuthinti ukondla kwabo okujwayelekile," kusho uNieh. "Lokhu kubalulekile ngoba ekwelapheni ukudla okuyimpoqo, sifuna ukumisa izingxenye zokudla ezingadingekile futhi sigcine nokudla okujwayelekile kungasebenzi."
"Kunesicelo esicacile sokuphazamiseka kwezinkinga zokudla kanye nokusebenzisa kabi izidakamizwa nokugembula ngoba kungenzeka kube yindlela evamile esebenza ngalezi zinhlobo zokuziphatha," kusho uPhillips.
E-mail ukuze Usosayensi, UTye uthe ilebhu yakhe manje isisebenzela ukucacisa kangcono ukusayinwa kwe-neuronal yokufisa okungatholakala ngesikhathi sangempela ukwenza izindlela zokungenelela zokumelana nokudla okuphoqayo nezinye izindlela zokulutha ngaphambi kokuqala.
JH Jennings et al., "Ukubona i-hypothalamic network dynamics for behaetitive kanye ne-menummatory behaviour," Iseli, doi.org/10.1016/j.cell.2014.12.026, 2015.
U-EH Nieh et al., "Ukuguqula imijikelezo ye-neural elawula ukufuna okucindezelayo kwe-sucrose," Iseli, doi.org/10.1016/j.cell.2015.01.003, 2015.
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