COMMENTS: Kafukufuku wodziwika bwino awiri wosonyeza kuti pali madera osiyana akamagwiritsa ntchito shuga - kapena monga YBOP amatchulira, 'a kusinja'. Zakhala zikuganiziridwa kuti zizolowezi zamakhalidwe zimachokera okha kusintha kwa "ma circuits abwinobwino". Izi zikachitika, zikuwonekeratu kuti pali 'magawo azakudya' omwe aliponso.
Izi zimapangitsa kukhala kosinthika. Ndi njira yolimbikitsira nyama kuti idye mopitirira muyeso chakudya chikapezeka. Maseketiwa amachokera ku hypothalamus, yemwenso ndi gawo lalikulu lazolamulira zakugonana, libido ndi zosokoneza. Sindikukayika kuti nyama zakutchire zimakhala ndi 'magawo azakudya' ogonana komanso chakudya. Kubereka ndizofunikira kwambiri pamatenda athu komanso mwayi wokulumikiza nthawi zambiri amakhala ocheperako komanso otalikirana kuposa mwayi wodya.
Pamodzi, kunenepa kwambiri ndi mtundu wa 2 matenda a shuga pakati pa mavuto aakulu a thanzi lathu, ndipo makamaka amachokera ku zomwe ambiri amachitcha "kuledzera" shuga. Koma kuthetsa vutoli ndi lovuta kwambiri kusiyana ndi kuthetsa vutoli, chifukwa limafuna kuchepetsa kudya zakudya zopanda thanzi popanda kulakalaka kudya zakudya zathanzi pakakhala njala.
Mu pepala latsopano mu Cell, akatswiri a sayansi ya mitsempha ku MIT adasokoneza njira ziwirizi m'magulu ndipo amasonyeza kuti kuletsa dera la ubongo lomwe silinadziŵike lomwe limalamulira kusakanikirana kwa shuga sikungasokoneze kudya kudya.
"Kwa nthawi yoyamba, tazindikira mmene ubongo umapangira shuga zosakanikirana ndipo tikuwonetsanso kuti zikuwoneka kuti ndizosiyana ndi kudya koyenera," anatero Kay Tye, wofufuza wamkulu pa Picower Institute for Learning. ndi Memory omwe adayambitsa njira zatsopano zophunzirira ubongo woyendetsera ubongo ndi nkhawa. "Tifunika kuphunzira dera ili mozama, koma cholinga chathu chachikulu ndicho kukhazikitsa njira zotetezeka, zosayenera kuti tipewe makhalidwe osadya, poyamba mu mbewa komanso potsiriza mwa anthu."
Kuledzera kumatanthauza kufunafuna mankhwala osokoneza bongo ngakhale kukumana ndi zovuta kusukulu, kuntchito, kapena kunyumba. Mankhwala osokoneza bongo "amabera" ubongo ndi malo achilengedwe opangira mphotho, malo amkati mwa gawo (VTA). Koma chakudya ndi mphotho yachilengedwe ndipo, mosiyana ndi mankhwala, ndichofunikira kuti munthu apulumuke, chifukwa chake sizikudziwika ngati kudya mopitilira muyeso chifukwa chakukakamizidwa komweko, kapena kuchokera ku chinthu china.
"Phunziroli likuyimira, ndemanga yanga, njira yodziwika bwino yopitilira kumvetsetsa zambiri zomwe zimapangitsa kuti anthu azikhala ndi makhalidwe abwino," anatero Antonello Bonci, yemwe ndi mkulu wa sayansi ku National Institute on Drug Abuse, yemwe sanachite nawo kafukufuku. "Ngakhale kuti pakhala pali maphunziro abwino kwambiri m'mbuyomo, ndikuyang'ana kutsogolo kovuta kugwiritsa ntchito mankhwala osokoneza bongo, iyi ndi nthawi yoyamba kuti phunziro likupita mwakuya komanso momveka bwino muzinthu zofanana zokhudzana ndi chizoloŵezi cha kudya. Kuchokera pamasulidwe omasuliridwa, njira yodabwitsa ya mitundu yosiyanasiyana yomwe ikugwiritsidwa ntchito mu phunziro lino inapangitsa kupeza kosangalatsa kwambiri: kuti kumwa mankhwala osokoneza bongo kumagwirizanitsa ndi dera losiyana ndi la neural kusiyana ndi thupi, kudya zakudya zathanzi. "
Phunziroli, Tye ndi wophunzira wake wophunzirayo, Edward Nieh, adalankhula za mgwirizano pakati pa VTA ndi ofanana ndi hypothalamus (LH), yomwe imayang'anira kudya. Koma chifukwa chakuti LH imayambanso makhalidwe ena osiyanasiyana ndipo imagwirizanitsa ndi zigawo zina za ubongo, palibe yemwe adasungunula dera loperekera chakudya ndi mphoto. Tye ndi Nieh poyamba adadziwika ndi ma neuroni omwe amalumikizana ndi VTA ndipo analemba zochitika zawo mwachibadwa m'magulu a ubongo, mothandizidwa ndi Gillian Matthews, asanayambe kuyesa zinyama. Electrodes analemba zochitika za neuroni izi panthawi ya ziweto.
Mbewa mwachibadwa zimakonda sucrose - ofanana ndi anthu omwe amakonda ma sodas olemera ndi shuga - kotero Nieh adaphunzitsa mbewa kufunafuna sucrose pa doko lotumizira pakumva ndikuwona chidziwitso. Makoswe ataphunzira kuneneratu za mphotho ya sucrose atangodziwikiratu, amangobweza mphothoyo pafupifupi theka la nthawi - zokhumudwitsa. Nthawi zina, mbewa mosayembekezereka zidalandira mphotho ya sucrose popanda chidziwitso - chodabwitsa. Kusiyanaku pakati pa zoyembekezera ndi zokumana nazo kumatchedwa cholakwika choneneratu za mphotho.
Zojambula za neural zinkasonyeza kuti mtundu umodzi wa ma LH neuroni wokhudzana ndi VTA unangokhala wotanganidwa chinyama chitaphunzira kupeza mphotho ya sucrose, kaya ayididi kulandira mphoto. Gawo lina la LH neurons, pa kulandila ndemanga kuchokera kwa VTA, linakumbutsa zomwe zimayankhidwa ku mphotho kapena kusamveka kwake.
Chotsatira, Nieh adagwira ntchito ndi wophunzira wa MD / PhD ku labata ya Tye, a Stephen Allsop, kuti asinthe mbewa kuti ziwonetsero za LH-VTA neural zizikhala ndi mapuloteni osawoneka bwino omwe amatha kuyambitsa kapena kutontholetsa ma neuron ndi kuwala, njira yotchedwa optogenetics. Kukhazikitsa ziwonetserozi kunapangitsa kuti anthu azidya mopitilira muyeso ndikuwonjeza kudya mbewa zomwe zinali zodzaza. Kuyambitsa njirayi kunachepetsa kufunafuna kwa sucrose komwe kumafanana ndi zosokoneza bongo, koma sikulepheretsa mbewa zomwe zinali ndi njala kudya chow wamba. "Zinali zosangalatsa chifukwa tili ndi mbiri yosonyeza momwe kufunafuna shuga kumeneku kumachitikira," akutero a Nieh, "ndipo titha kuyendetsa kapena kupondereza mchitidwe wokakamizawo posintha mosiyanasiyana magwiridwe antchito a neural."
Tye, yemwenso ndi Whitehead Career Development Assistant Pulofesa adati: "Ofufuza za mankhwala osokoneza bongo aganiza kuti kusintha kuchoka kuzolowera kuchita zizolowezi mpaka kukakamiza ndi njira yokhayo yosinthira, Dipatimenti ya MIT ya Ubongo ndi Sayansi Yoganizira. "Tsopano tili ndi umboni wosonyeza kuti kusinthaku kukuyimiridwa mdera la LH-VTA."
Nieh, akugwira ntchito ndi a Matthews, a postdoc mu lab ya Tye, adawonetsanso kuti ma LH neurons amatumiza mitundu yosakanikirana (glutamate) ndi inhibitory (GABA) ku VTA. Koma mosiyana ndi chiyembekezero, anali ma inhibitory sign, osati omwe amasangalatsa, omwe adayambitsa ntchito yodyetsa mbewa. Pomwe ziwonetsero za GABA zokha zidakhazikitsidwa, mbewa zimachita zodabwitsa, ndikulumira pansi pa khola ndikutulutsa zodzitengera kubweretsa chakudya pakamwa ndikuchifuna. (Anali atadyetsedwa, motero sanali ndi njala.) "Tikuganiza kuti ziwonetsero za glutamatergic zimawongolera momwe ziwonetsero za GABAergic, zikuwunikira zomwe zili zoyenera kukukutani," akutero Nieh. "Zinthu zonsezi ziyenera kugwirira ntchito limodzi kuti zithandizire kudya."
"Izi ndizofunikira kwambiri kumunda, chifukwa izi ndi zomwe sitinazidziwe kale," adatero Bonci, "ndipo amatha kusintha njira yomwe timayendera mankhwala osokoneza bongo."
Ofufuzawo adadziwanso kuti mapuloteni ambiri amatha kuperekedwa pa VTA. Chitsulo chilichonse cha LH neuroni chimagwirizanitsa ndi dopamine- ndi Ganga-producing neurons mu VTA. Labu tsopano ikufufuzira momwe zizolowezi zodyetsa ndi zopaka asprose zimasiyana mosiyana ndi mtundu wa chithunzithunzi cha neuron.
Kafukufukuyu adayambitsidwa monga gawo la Mphoto ya New Investigator ya Tye ya 2013 NIH, ndi cholinga cha nthawi yaitali chokhazikitsa njira yatsopano yothetsera kunenepa kwambiri komwe ingagwiritsidwe ntchito ku matenda ena a mphuno. Zina zowonjezera ndalama zinachokera ku magulu ambiri a anthu ndi apadera, kuphatikizapo a NSF Graduate Research Fellowship, Integrative Neuronal Systems Fellowship, ndi Dipatimenti Yophunzitsa ku Neurobiology ya Kuphunzira ndi Kukumbukira. Kara N. Presbrey, Christopher A. Leppla, Romy Wichmann, Rachael Neve, ndi Craig P. Wildes, onse a Picower Institute, adathandizanso pa ntchitoyi.
Asayansi atanthauzira za neurons zomwe zimayambitsa kudya moyenera kwambiri pazomwe sizinachitikepo
By Anna Azvolinsky | | January 29, 2015
Magulu awiri ochita kafukufuku odziimira pawokha adatanthauzira anthu ambiri a neurons mu hypothalamus omwe ali ndi udindo wa chakudya-monga-mphoto kukakamiza, koma mwina sikofunika kuti apangitse kudya kuti apulumuke. Magulu awiriwa adafalitsa zomwe adapeza lero (January 29) Cell.
"Awa ndi mapepala akuluakulu omwe amayamba kufotokozera kuti [hypothalamus] ndi zovuta komanso zogwirizana ndi zizindikiro zinazake zomwe zimatha kupanga zotsatira zamakhalidwe abwino," adatero Ralph DiLeone, katswiri wa sayansi ya ubongo ku Yunivesite Yale yemwe sanachite nawo ntchitoyi.
Kugwiritsa ntchito optogenetics, katswiri wa zamaganizo Garret Stuber pa yunivesite ya North Carolina, chapel hill, ndi anzake anapeza kuti GABAergic neurons m'malo osakanikirana hypothalamus (LH) adatsogolera mbewa kuti azidyetsa mobwerezabwereza, pamene kulepheretsa ntchito za neuroni izi zinalimbikitsa mbewa kuti zisadye mopitirira muyeso. Ma neuroniwa anali osiyana ndi anthu ena a neuronal mu LH omwe poyamba ankakhudzidwa ndi kudya ndi zina zokhudzana ndi mphoto. Pamene ma neuroniwa anali ataphatikizidwa ndi majini, mbewazo sizinali zolimbikitsidwa kuti zipeze mphoto ya calorie yamadzi. Asayansi awonetsanso kashiamu yodziwika ndi mazanamazana a GABAergic neurons kamodzi pamagulu osasunthirapo mwa kuika makina ochepa kwambiri mu LH ndi kuikapo microscope yazing'ono zopangidwa ndi tizilombo toyambitsa matenda. Kujambula kwa calcium kunasonyeza anthu osiyanasiyana a GABAergic neurons omwe amagwira ntchito yoyamba pa mphotho ya chakudya kapena pamene mbewazo zimagwiritsa ntchito mphuno zawo-chizindikiro cha chidwi pa chakudya-koma kawirikawiri pazochitika zonsezi.
Kujambula kwa calcium mu vivo kumapangitsa ochita kafukufuku kuwerenga ntchito za neuronal pamtunda waukulu-m'madera ena a ubongo, adatero DiLeone. Njirayi inakhazikitsidwa ndi Ma laboratory a Mark Schnitzer ku yunivesite ya Stanford. "Zaka zisanu ndi chimodzi zapitazo, sitinakhale nayo imodzi ya matekinoloje awa-genetic ablation, optogenetics, mu vivo imaging," Paul Phillips, katswiri wa sayansi ya sayansi ku yunivesite ya Washington, adanena Wasayansi. "N'zosadabwitsa kuona labu la Stuber likuyika pamodzi pamodzi kuti ayankhe mafunso ofunika kwambiri a sayansi."
Nkhono za LH ndizosiyana, ndipo zimadziwika kuti zimakhudzidwa ndi makhalidwe okhudzana ndi mphoto monga kudya, kumwa, ndi kugonana. Koma kufotokozera za mitundu yosiyanasiyana ya neuroni m'dera lino la ubongo kwakhala kovuta. "Takhala ndi zofufuza zamagetsi zoposa zaka zoposa 30 tsopano, koma sitinadziwe kuti ndi zotani zomwe tinkakondweretsa komanso ngati tizilombo toyambitsa matenda timachokera ku LH kapena zomwe zikudutsa mpaka optogenetics anakhalapo, "adatero Roy Wise, katswiri wa sayansi ya zachipatala ku National Institute on Drug Abuse amene sanachite nawo ntchitoyi.
"Pali chisangalalo m'munda wa sayansi ya chidziwitso mu vivo imaging chifukwa imatithandiza ife, nthawi yoyamba, kuti tiphunzire momwe ntchito ikugwiritsidwira ntchito mkati mwa maselo ofanana," anawonjezera Stuber.
Phunziro lachiŵiri, lotsogoleredwa ndi MIT neuroscientist Kay Tye, ofufuza adazindikira magawo awiri osiyana amitsempha yolumikizana ndi LH ndi midbrain's ventral tegmental area (VTA), yomwe imadziwika chifukwa chogwirira ntchito mphotho. Kaya ma neuron mu ziwonetsero za LH-VTA amayankha shuga wokha, kapena kuti atenge shuga sanadziwike, atero a coauthor Edward Nieh, wophunzira wophunzira maphunziro mu laboratori ya Tye. "Tsopano tikudziwa kuti pali mitundu yambiri ya zamoyo zomwe zimatulutsa [shuga] komanso [shuga]."
Pogwiritsa ntchito kusiyana pa njira ya optogenetics, gululo linangogwiritsa ntchito kokha ndi neurons mu LH yomwe ikugwirizana ndi VTA. Pofufuza mosasunthika makoswe, gululo linapeza kuti ma neurons akugwirizanitsa LH ndi VTA adayankhidwa panthawi yofuna kupeza mphotho ya shuga, pokhapokha ngati mphothoyi inapezedwa. Kuletsa dera limeneli kunachepa kokha kufunafuna shuga kosayenera-osati khalidwe labwino lodyetsa-m'magulu awa. Kulimbikitsa zokhazokha zokhudzana ndi GABAergic m'dera lino zimapanga makhalidwe osadziwika: nyama zimatchera pansi kapena malo opanda kanthu muzipinda zawo pamene panalibe chakudya. Ndipo kulimbikitsa ma neuroniwa kunachititsanso kuti khalidwe lachikale lachigonjetso lagonjetsa-kulandira mphotho ya shuga, komanso kuwonjezeka kwambiri.
Niehh anati: "Tikhoza kuchepetsa kufunafuna zakudya zopatsa thanzi koma sizimakhudza chakudya chawo. "Izi ndizofunikira chifukwa chokhalitsa khalidwe lofuna kudya, timangofuna kuti tisiye kudya zakudya zopanda phindu komanso kuti tizidya moyenera."
"Pali njira yowonetsera yomwe ikugwiritsidwa ntchito pofuna kudyetsa matenda komanso kugwiritsira ntchito mankhwala osokoneza bongo komanso njuga chifukwa zingakhale njira yamba yomwe imayambitsa makhalidwe amenewa," anatero Phillips.
Mu imelo ku Wasayansi, Tye adati labu yake ikugwira bwino ntchito yolemba chizindikiro cha neuronal chokhumba chomwe chikhoza kuwonedwa panthawi yeniyeni kukonza njira zothandizira kuletsa kudya kwambiri ndi makhalidwe ena osokoneza bongo asanayambe.
JH Jennings et al., "Kuwonetsa zochitika zamakono zokhudzana ndi zokhudzana ndi zikhumbo zokhutira ndi zoyipa," Cell, doi.org/10.1016/j.cell.2014.12.026, 2015.
EH Nieh et al., "Kukonzekera maulendo a neural omwe amachititsa kuti munthu asamangokhalira kufunafuna," Cell, doi.org/10.1016/j.cell.2015.01.003, 2015.
;