Ulawulo lwe-Sucrose ukuzilawula kunye nokusebenza kwe-CNS kwi-rat (2011)

. I-2011 Aprili; I-300 (4): R876-R884.

Ishicilelwe kwi-intanethi 2011 Feb 9. ikhonkco:  I-10.1152 / ajpregu.00655.2010

PMCID: PMC3075076

Abstract

Ngaphambili siye saxela ukuba ulawulo lwe-insulin kwi-arcuate nucleus ye-hypothalamus iyancipha inkuthazo ye-sucrose, ihlolwe ngumsebenzi wokuzilawula, kumagundane. Ngenxa yokuba ipateni yenkqubo ye-central system ye-activation (CNS) ngokudibana nokuzilawula ayikavavanywa, kwisifundo esikhoyo, silinganise ukubonakaliswa kwe-c-Fos njengesalathiso sokusebenza kwe-neuronal. Siqeqeshe iigundane ukushicilela nge-bar-sucrose, ngokwe-ratio eqingqiweyo (i-FR) okanye ishedyuli eqhubekayo (PR) kunye nengcaciso yemephu ye-c-Fos yokugonywa kwi-CNS, xa kuthelekiswa nentetho ye-c-Fos kulawulo oluphathwayo. Siqwalasele intetho ekhethekileyo ye-c-Fos kwi-medial hypothalamus (i-arcuate, iparaventricular, i-retrochiasmatic, i-dorsomedial, kunye ne-ventromedial nuclei) ngokunxulumana nokuqala kokusebenza kwe-PR, kunye nokubonakaliswa kwe-c-Fos kwi-hypothalamus ye-lateral kunye ne-nucleus yebhedi ye-stria terminalis ngokunxulumana nokuqala kokusebenza kweFR. I-c-Fos expression yonyuswe kwii-nucleus accumbens zazo zombini i-FR kunye ne-PR rats. Isifundo sethu sigxininisa ukubaluleka kokubini kwe-hypothalamic energy homeostasis circry kunye ne-limbic circry ekusebenzeni komsebenzi wokuvuzwa kokutya. Ngenxa yendima ye-medial hypothalamus kulawulo lwebhalansi yamandla, isifundo sethu sibonisa ukuba le setyhula inokuba negalelo kwimbuyekezo yomgaqo ngaphakathi komxholo omkhulu wamandla we-homeostasis.

Internet: umvuzo wokutya, i-c-Fos, i-hypothalamus

Isiphathamandla se-mesolimbic dopaminergic (DA), kubandakanya indawo yokwahlula i-ventral (VTA) kunye noqikelelo kwiziza kunye neendawo zecortical, zichongiwe njengendima ebalulekileyo kwizinto ezikhuthazayo nezivuzayo kwiiklasi ezininzi zamachiza okuphathwa gadalala (, -, , ). Uphando lwakutsha nje elebhu yethu kunye nabanye bacebisa ukuba le setyhula ngokufanayo idlala indima ebalulekileyo kwimicimbi ekhuthazayo okanye evuzayo yokutya. Ukusebenzisana kunye nokusebenza komzimba kunye nokujikeleza okulawula amandla e-homeostasis kucetyiswa ziingxelo zokutshintshwa komvuzo wokutya ngenqanaba lesondlo sezilwanyana (, , , ). Ukutshintshwa komvuzo, kubandakanya nomvuzo wokutya, ngesondlo okanye imeko yemetabolism, kuphenjelelwa ngamandla zizibonakaliso ze-neural kunye ne-endocrine, kubandakanya i-insulin (), leptin (, , , , ), ghrelin (), i-melanin-egxila kwi-hormone (MCH) (), kunye ne-orexin (, ) Ubukho bee-receptors, ukusebenza kwe-biochemical ne-cellular, kunye ne-vivo okanye indlela yokuziphatha kwezi mpawu kwinkqubo ye-nerve system (CNS) ibonakaliswe kakhulu kwiminyaka yakutshanje.

Ukujikeleziswa kwe-limbic eyongeziweyo kubonakalisiwe kudlala indima ekondleni nasemvuzweni wokutya (, , ). Nangona kunjalo, kukho iindawo ezongezelelweyo ezinegalelo le-CNS. Ngokukodwa, i-lateral hypothalamus (LH) kudala yaziwa njengendawo yokulamla yokuziphilisa kunye nokuziphatha okuzikhuthazayo (, ). I-Orexinergic neurons kunye ne-leptin signing kwi-LH ichongiwe njengebalulekile ukondla kunye nomvuzo wokutya (, , ). Kutshanje siqwalasele ukuba i-insulin ilawulwa nokuba kukwimo yesithathu yecypothalamus (i-ARC) inokunciphisa ukuzilawula, kodwa ulawulo lwe-insulin kwi-VTA okanye kwi-nucleus accumbens alunampembelelo kule paradigm yomvuzo othile.). Ke ngoko, kuyavela ukuba iindawo ezininzi ze-hypothalamic zinokudlala indima ebalulekileyo ekufuneni ukutya kunye nasekufumaneni, kwaye ngokuhambelana noku, umntu uya kutyhila ukuba imimandla ye-hypothalamic yenziwa ngamandla ngokunxulumene nokuzilawula kokutya. Ukuqala ukuvavanya le hypothesis, sibeke imephu ye-c-Fos kwi-CNS yeempuku eziqeqeshelwe ukuzilawula kwetyala, emva koqeqesho oluqingqiweyo (FR), okanye emva koqeqesho oluqhubekayo (PR), umsebenzi olungeleleneyo. kuvavanika inkuthazo ().

IMPAHLA NENKQUBO

I zifundo.

Izifundo yayiziigundane ezingamadoda zeAlbino (325-425 g) ezivela eSimonsen (eGilroy, CA). Iigundane zigcinwe kwi-chow ad libitum. Zagcinwa kumjikelo we-12: 12-h ukukhanya-mnyama kumjikelo nezibane kwi-6 AM kwaye baqeqeshwa kwaye bavavanywa phakathi kwe-7 AM kunye nemini, kwimeko yasemva kwento eyenziwayo nasemva kokubanjwa. Zonke iinkqubo ezenziwa kwiigundane zilandele iZiko leSizwe lezeMpilo kwezikhokelo zokhathalelo lwezilwanyana kwaye zamkelwa yiKomitana yoKhathalelo lweZilwanyana kunye nokuSebenzisa yeKomiti yoPhando noPhuhliso kwiNkqubo yoKhathalelo lwezeMpilo ye-VA Puget.

Zenzele ukuzilawula.

Inkqubo ibisekwe kwindlela yethu epapashiweyo () kwaye zaziqhutywa kwiigundane ezityisiweyo. Olu vavanyo lubandakanya izigaba ezithathu: ukuziqhelanisa nokuzilungiselela ukuqala ngoqeqesho, ukuqeqeshwa ngo-FR, kunye noqeqesho oluqhubekayo (PR) kusetyenziswa i-algorithm yeRichardson neRoberts (). I-algorithm ye-PR ifuna i-1, 2, 4, 6, 9, 12, 16, 20, 28, 36, 48, 63, 83, 110, 145, 191, 251, XNUM njl. njl.). Iigundane ziqeqeshelwe ukuzilawula ngokwazo i-5% ye-sucrose (umvuzo we-0.5 ml) oziswe kwindawo yokwamkela amanzi. Iibhokisi ezisebenzayo, ezazilawulwa yinkqubo yeMedi Associates (Georgia, VT), zazinee-levers ezimbini, kodwa inye kuphela i-lever (i-lever esebenzayo esebenzayo) esebenze kwimpompo yokufaka. Imithombo yosasazo yomnye umkhweli (umntu ongasebenziyo, osebenza esimeyile) nayo yabhalwa. Njengoko sele sibonile ngaphambili, inani loxinzelelo kumatshini osebenzayo lalingaphantsi kakhulu (ngaphantsi kwe-10 yemishini yokushicilela / iseshoni). Isisombululo se-sucrose sasihanjiswa kwisitofu esiyi-fluid sokusetyenziswa komlomo (iMed Associates, iSt. Albans, VT). Uqeqesho lokuqala lwaluqhutywa ngexesha leeseshini ze-1-h phantsi kweshedyuli yokuqhubeka kokuqiniswa (i-FR1: nganye yomatshini wokushicilela waqiniswa). Iseshoni nganye yaqala ngokufakelwa kwelever esebenzayo kunye nokukhanya kwesibane sendlu emhlophe eseleyo kuyo yonke iseshoni. Ithoni ye-5-s (2900 Hz, 20 dB ngasentla ngasemva) kunye nokukhanya (i-7.5 W emhlophe ukukhanya emhlophe kwi-lever esebenzayo) i-cue ye-cue ye-concrete ehambisanayo ehamba kunye nokuhanjiswa kwemivuzo, kunye nexesha le-20-s ukuqala ukuqala ngokuzisa i-sucrose. Uqeqesho lwe-FR lwenziwa kwiintsuku ze-10; Ukuphendula okuzinzileyo kufezekiswa kwiseshoni yesihlanu. Uqeqesho lwe-PR lwenziwa ngobuninzi be-3 h / usuku lweentsuku ze-10. Iiseshini ze-PR zaphela emva kwe-30 ye-min ye-lever esebenzayo yokuphendula, ngeloxesha ukukhanya kwendlu kucinyiwe ngokuzenzekelayo kwaye i-lever esebenzayo yarhoxiswa; Iigundane zazikhutshelwa ngaphandle kwamagumbi zize zibuyele ezindlini zazo. "Ixesha lokuyeka" kuxelwe ngaphakathi 2 Table imele ixesha apho inkqubo ibicinyiwe; ke, umshicileli wokugqibela osebenzayo we-lever ngewenzekile nge-30 min ngaphambi kwexesha lokumisa. Idatha yokuziphatha (2 Table) Zibonisa izilinganiselo ze iiseshini 6-10 yoqeqesho lwe-FR, kwaye iiseshini 1-9 yoqeqesho lwe-PR. Iigundane ezazilawulwa ngesandla zithathwe kwigumbi lezindlu zaza zabekwa kwigumbi elinabasebenzi abacocekileyo kunye nokukhanya kwendlu kwi-60 min, ngaphakathi kwigumbi lenkqubo, ukulingisa ukuphatha kunye namava egumbi kwiirati ezizisebenzelayo. Abazange banikwe nantoni na yokutya okanye yokusela ngelixa besebhokisini ezisebenzayo, kwaye bengafikeleli kwizondlam.

Ithebula 2. 

Iiparamitha zokuzigcina kwiigrada ze-FR kunye ne-PR

Ngosuku lokugqibela, iigundane zabekwa kumagumbi ngokweentsuku zoqeqesho kwaye zagcinwa kumagumbi e-90 min, emva koko zasuswa, kwi-anesthesia, perfusion, kunye ne-immunohistochemistry elandelayo. Iigundane zolawulo nazo zaziswa kwigumbi lenkqubo kwaye zigcinwa kwigumbi elisebenzayo elicocekileyo, ngokweentsuku zoqeqesho, kwimizuzu engama-90, emva koko zanikwa i-anesthetised and perfused. Ngokukhawuleza emva kweseshoni yokugqibela ye-90-min, iigundane zazifakwe i-isoflurane inhalation kwaye zenziwa nge-0.9% NaCl elandelwa sisisombululo se-4% se-paraformaldehyde. Ixesha le-anesthetic kunye ne-euthanasia lalisekwe kwikhosi yexesha eyaziwayo yokubonisa okuphezulu kweprotein ye-c-Fos kwi-90-120 min emva komsitho. Ke, intetho ye-c-Fos iya kubonisa ukwenziwa kwe-CNS ekuqaleni kokuziphatha, kunokuba sisiphumo sokufumana kwezilwanyana lo msebenzi kunye nokufaka i-sucrose. Iingqondo zisuswe zaza zalungiswa zanikezelwa ngeparaformaldehyde kangangeentsuku ezininzi; emva koko babekwa kwi-20% sucrose-PBS, emva koko babekwa kwi-30% ye-sucrose-PBS isisombululo. Ubuchopho babekwa kwicandelo le-cryostat (Leica CM 3050S cryostat) ye-immunohistochemistry.

c-Fos immunohistochemistry kunye nenani.

Sisebenzise indlela yethu esekwe ukwenza i-protein ye-c-Fos engasebenziyo kumacandelo obuchopho (). Isikrini sokuqala sobuchopho sobuchopho yonke senzelwa ukuvakaliswa kwe-c-Fos. Amacandelo e-slide-akhweliswe i-12-μm amacandelo e-corono-egqityiweyo-ahlanjwe amaxesha e-3 kwi-PBS (Oxoid, Hampshire, UK). Amacandelo ayevinjelwe i-1 h kubushushu begumbi kwi-PBS equlathe i-5% ibhokhwe eqhelekileyo okanye iesum yedrum. Amacandelo ahlanjwa kaninzi kwi-PBS kwaye afakwa ubusuku bonke kwi-4 ° C kwizisombululo zokuqala zomntu ezenziwe kwi-PBS. Amacandelo ahlanjwa kathathu kwi-PBS kwaye emva koko afakwa ebumnyameni kwigumbi lokushisa kwisisombululo se-antibody sesibini esenziwe kwi-PBS ye-1 h. Amacandelo ahlanjwa emva koko kwi-PBS kwaye agqunywe kwaye agqunywe atyibilika eVectashield iseti eqinileyo yokulalisa (iVector Laboratories, iBurlingame, CA) ephakathi phakathi. Imifanekiso yedijithali yamacandelo ifunyenwe kusetyenziswa ikroskopu ye-Nikon Eclipse E-800 ye-fluorescence eqhagamshelwe kwikhamera ye-Optiphot kunye nokusebenzisa i-Image Pro Plus (Media Cybernetics, Silver Spring, MD) isoftware.

Emva koko, sajonga kwinani eliqingqiweyo leendawo ezibonakalisa umahluko ocacileyo phakathi kweemeko, ubungakanani, kunye ne-neuronal phenotyping. Ngokukhethekileyo, sajonga kwi-nucleus accumbens engundoqo kunye neqokobhe (NAc); i-nucleus yangaphambi kwebhedi kunye ne-posterior ye-stria terminalis (aBNST, pBNST); imimandla ye-medial hypothalamic [[i-ventromedial nucleus (VMH), dorsomedial hypothalamus (DMH), i-nucleus ye-patus (PVN), indawo ye-retrochiasmatic (RCh), kunye ne-ARC]; i-hypothalamus (LH) ye-lateral, kubandakanya imimandla e-dorsal kunye ne-ventral kunye ne-pervivical (peF); I-VTA; isisu sobuchopho [umthambo ongaphantsi kwe-olive, i-hypoglossal (nXII) ye-patus yodwa, kunye ne-C1 / A1 adrenaline / noradrenaline nuclei. Icandelo le-Atlas-matching 12-μm lavavanywa ukucaciswa kwe-c-Fos kunye nenani kumacandelo afanisiweyo kunye nemimandla, ngokusekwe kwi-atlas yePaxinos neWatson (). Nceda ubone 1 Table kulungelelaniso oluthile lwe-stereotaxic. Eyona nto kugxilwe kuyo ubukhulu becala kukuthelekisa umsebenzi ngamnye wokuziphatha kunye nokulawulwa kwawo (PR vs. PRC; FR vs. FRC). Ukwandisa iiyantlukwano ezinokwenzeka ngokusekwe kwimigaqo yolawulo yokuziphatha, iimeko zencopho yabasebenzi abavela kwi-PR kunye namaqela e-FR bakhethwa ukuba bahlaziye. Ke, i-4 / 12 PR kunye ne-3 / 12 FR rats ziye zahlalutywa: Ezi rayisi zazinenombolo ye-lever esebenzayo (isiphelo sendlela yokuziphatha) eyayinkulu kunxaxhile yomgangatho omnye ngaphezulu kwendlela yeqela labo lokuziphatha. Ukufakwa kwegundane kulawulo (i-5 PRC kunye ne-3 FRC amagundane, akhoyo kwigumbi lenkqubo ngaxeshanye ne-FR okanye iigundane ze-PR) kwahlaziywa. Iqela elongezelelweyo lamagundwane amathathu lathatyathwa kwinkqubo ye-FR ("i-Frext") ukulinganisa ixesha elongeziweyo lenkqubo ye-PR (okt, iyonke imihla ye-20, njengoko iigunds ze-PR zithathwa kwi-FR kwaye ke kwi-PR) ukuvavanya ukuba ingaba Umahluko phakathi kwe-FR kunye ne-PR kubangelwe ngumsebenzi wokuziphatha okanye ubude benkqubo. Iingqondo ze-FRext azange zihlalutywe kwaye zihlolwe ngokulandelelana, kodwa imimandla ethile yomdla yathatyathwa kunye namanye amaqela amane, ukuvumela ukuthelekiswa ngokuthelekiswa, njengoko kubonisiwe ngokuthe ngqo kwiziphumo.

Ithebula 1. 

I-Stereotaxic zidibanisa ukulungelelaniswa kwe-c-Fos

Ukufumana ubungakanani (kwi-40 × enkulu), imimandla ehambelana nemimandla ithethwe. Isoftware ye-ImagePro Plus (iMidiya yeCybernetics) yasetyenziswa ukuthimba umfanekiso wendawo oyifunayo. Indawo yenzelwe ukubalwa, kwaye isiseko somgangatho wokubala eselwayo wasekwa. Indawo efanayo kunye nomva (umkhombandlela) wasetyenziselwa amacandelo avela kumaqela achaphazelekayo, kwaye ukubalwa kwesoftware yeeseli ezakhayo (inani) laqhutywa kwiseshoni enye kuwo onke amaqela ovavanyo, ukuthintela iinguqu phakathi kweseshini kuseto lwasemva. Uhlalutyo lweenkcukacha-manani, ukubalwa kuthathwe kumgangatho ngamnye kuphela ukuba kuyahambelana okanye kugqitywa ngamacandelo kwindawo nganye (njengoko kuchaziwe ku 1 Table) zazifumaneka; Idatha yendawo ethile ayithatyathwanga kumgangatho ukuba akukho ukumelwa kwamazwe amabini engaphelelanga.

Uhlalutyo oluphindwe kabini olunelebhedi ye-immunofluorescence.

Amacandelo obuchopho athathwe kwiigundane apho i-c-Fos yalinganiswa khona, yelebheli ephindwe kabini ene-immunohistochemistry. Kuba sasinganqweneli ukuphazamisa indlela yokuziphatha kwezilwanyana, azange zenziwe kwangaphambili nge-colchicine ukulungiselela ukubonwa kwe-peptide neurotransmitters. Ke ngoko, ukubonwa kwe-neuronal phenotypes esebenzayo ngokudibeneyo nomsebenzi wokuzilawula wawunomda. Nangona kunjalo, ukuqala kuvavanyo lwee-phenotypes ze-activated neurons kwiindawo ezininzi ze-CNS, imifanekiso yedijithali (efunyenwe njengoko kuchaziwe kwicandelo elingentla) yathathwa nge-20 ×, 40 ×, okanye i-60 × (njengoko kubonisiwe kwiintsomi zamanani) . Inkqubo yokubala kabini ye-glutamate decarboxylase (GAD), tyrosine hydroxylase (TH), CRF, neuropeptide Y (NPY), i-peptide enxulumene ne-Agouti (AgRP), kunye ne-tryptophan hydroxylase yayithelekiswa nokuvavanywa kwe-c-Fos-immunoreactivity kuyo eyakhe, ngaphandle kokuba umxube we-c-Fos-Ab kunye nolunye ulwahlulo olusisiseko lwalusetyenziselwa ukufukama ngobusuku obungu-4 ° C; Ngokunjalo, zombini ii-antibodies zesibini zazikwisisombululo esinye kwaye zafukanyiselwa i-1 h ebumnyameni kwiqondo lobushushu kwigumbi. I-20-min 50% ye-ethanol yokuhlamba ngaphambi kwenyathelo lokuthintela lalisetyenziselwa uvavanyo lwe-orexin. Ukuvavanywa kokuqala kokusebenza kwenzelwa ukumisela ukuxutywa ngokufanelekileyo kwee-antibodies eziphambili. Iintsholongwane zokuqala ezazisetyenziswa yayiyi-anti-c-Fos yomvundla (1: 500) (sc-52) kunye ne-anti-c-Fos yegundane (1: 800) (zombini zivela eSanta Cruz Biotechnology, eSanta Cruz, CA); i-anti-GAD yegundane (1: 1,000), igundane elichasene ne-tyrosine hydroxylase (1: 500), kunye neegusha ezichasene ne-tryptophan hydroxylase (zonke zivela eChemicon, eTemecula, CA); umvundla ochasene neCRF (1: 500) (isipho esivela kuGqirha Wylie Vale, iZiko leSalk, CA); umvundla anti-NPY (1: 1,000), umvundla anti-AGRP (1: 1,000), kunye nebhokhwe anti-orexin A (1: 5,000) zonke zivela ePhoenix Pharmaceutical (St. Joseph, MO). Amachiza omzimba asetyenziswayo yayiyibhokhwe echasene nomvundla weCy3 okanye i-anti-mouse (iJackson Immunoresearch; West Grove, PA), i-Alexa Fluor 488 yebhokhwe echasene nempuku okanye anti-umvundla okanye iesile ngokuchasene neegusha IgG (Molecular Probes, Eugene, OR) ; zonke izilwa-buhlungu eziziisekondari zahlanjululwa ngo-1: 500. I-c-Fos / MCH yokugonywa kabini kwenziwa uvavanyo ngokulandelelana; okokuqala, kwi-MCH (1: 2,500 antibody yokuqala, iMillipore) ene-Alexa-488 yebhokhwe anti-rabbit (1: 500) yesibini. Izilayidi ziphinde zaphinda zaphindwa zenziwa nge-5% ye-serum yebhokhwe kwaye yagcwala i-anti-c-Fos (1: 500) kunye ne-cy3-yebhokhwe anti-umvundla njenge-antibody yesibini. I-20-min 50% ye-ethanol yokuhlamba ngaphambi kokuba inyathelo lokuvimba lisetyenziselwe uvavanyo lwe-MCH.

Uhlalutyo lweenkcukacha-manani.

Idatha yeqela ibonakaliswa njengendlela ± SE kwisicatshulwa, iitafile kunye namanani. Ukubaluleka kuchazwa njenge P 0.05. Uthelekiso lweenkcukacha-manani lwenziwa phakathi kwamaqela olingo (i-FR kunye ne-PR) okanye phakathi kwamaqela olingo kunye nolawulo oluhambelanayo (i-PR ngokuchasene ne-PRC; i-FR kunye ne-FRC) kusetyenziswa i-Student engafakwanga t-uvavanyo. I-Pearson yokulungelelanisa ii-coefficients phakathi koomatshini bokushicilela abasebenzayo kunye ne-c-Fos expression kwimimandla eyahlukeneyo yobuchopho, kunye nokunxibelelana kwe-c-Fos expression phakathi kwemimandla eyahlukeneyo yobuchopho phantsi kweemeko ezifanayo zovavanyo, kwabalwa kusetyenziswa iStatPlus: mac LE inkqubo yohlalutyo lweenkcukacha kwiinguqulelo zeMac OS Ngo-2009 nguAnalystSoft. Sivavanye ulungelelwaniso lomgama (Pearson's R statistic) phakathi kwentetho ye-c-Fos kwimimandla eyahlukeneyo ye-CNS. Siphinde savavanya unxibelelwano phakathi kwembonakalo ye-c-Fos kwimimandla eyahlukeneyo ye-CNS esebenzayo kunye nokuziphatha. Idatha ye-FR kunye ne-PR evela kwiigundane, ekwenziwa kuyo inani le-c-Fos, yayisetyenziselwa lo malungiselelo.

IINKCUKACHA

c-Fos ubungakanani.

Njengoko sele sibonile ngaphambili, inani loxinzelelo lwe-lever olusebenzayo lwalukhulu kakhulu ekusebenzeni kwe-PR vs.2 Table), kwaye inani lemivuzo ye-sucrose lalilikhulu ngexesha lokusebenza kwe-FR. Ubude beseshini kwiigundane ze-PR zazimalunga ne-90 min (ixesha lokuma-30). 3 Table uluhlu lwe-C-Fos ukubalwa kweeseli ezingafunekiyo kuyo yonke imimandla ye-CNS apho kwenziwa khona ubungakanani. Ipateni yentetho ye-c-Fos ye-FR kunye ne-PR yeishwankathelo ishwankathelwe Ikhiwane. 1. Kwakukho kusebenze okubalulekileyo kwe-medial hypothalamus (MHesesi, eyindibaniselwano ye-ARC, PVN, RCh, DMH, kunye neVMH) yeempuku ezibandakanyeke kwi-PR lever icinezela i-sucrose, kodwa akukho kusebenze ngokubanzi kumagundwane abandakanyeka kwi-lever ye-FR yokucinezela i-sucrose, ngokuthelekiswa nolawulo olufanelekileyo. Ngaphakathi medial hypothalamus ye-PR rats, oku kusebenze kwenzeke kwi-PVN, ARC, kunye neVMH (Ikhiwane. 2). Ukucinezelwa kwe-lever ye-FR, kodwa hayi ukucinezela i-PR lever, bekudityaniswa nokusebenza okukhulu ngaphakathi kwe-LH (ngokusekwe ekusebenzeni ngaphakathi kwecandelo lokudibana). Zombini iingcinezelo ezisebenzayo ze-lever kunye ne-hypothalamic c-Fos expression zazithelekiswa phakathi kwamaqela e-FRext kunye ne-FR (MHesesi, I-946 ± 26 kunye ne-911 ± 118; I-ARC, 176 ± 18 kunye ne-186 ± 10; I-LHesesi, I-468 ± 79 kunye ne-378 ± 34; I-LHpeF, 200 ± 31 kunye ne-173 ± 15, ngokulandelelana), iphakamisa ukuba umahluko kwipateni yentetho phakathi kwamaqela ka-FR kunye ne-PR ayinxulumene nexesha lokuqeqeshwa / amava kodwa ubume bomsebenzi onamandla. Kwiqela le-FR, kukho ukonyuka okukhulu kwentetho ye-c-Fos kwi-BNST, eqatshelwe kuzo zombini i-aBNST kunye ne-pBNST. Ukucinezela kokubini kwe-FR kunye ne-PR kwakudityaniswa nokunyuka kwe-c-Fos-immunopositive neurons kwigobolondo le-NAc; ukubalwa kwe-c-Fos kukonyuswe kakhulu kubunzulu be-NAc ukusuka kumagundwane abandakanyeka kwi-FR lever Pressing, eneempawu ezingenamsebenzi zokunyusa ukubonakaliswa kwe-c-Fos kumagundane abandakanyeka kwi-PR lever Pressing. I-c-Fos ayinyuswanga kwi-VTA nomsebenzi we-PR, nangona intsingiselo engancediyo kulwando ibonwa nomsebenzi we-FR. Okokugqibela, i-c-Fos yanda kakhulu kwi-hypoglossal (cranial nerve XII) kwi-stem yengqondo yamagundane aqeqeshelwe i-PR, kodwa hayi ngoFR.

Ithebula 3. 

Ukucaciswa kweCF kwi-CNS
Umzobo 1. 

I-c-Fos immunopositive-cell count in central system system (CNS) mimandla yomlinganiso osisigxina (FR)-kunye nomlinganiso oqhubekayo (PR) -ukusebenza kweegundane ezinxulumene nolawulo. Amanani eseli olawulo lweFR-FRC) kunye nolawulo lwe-PR (PRC) asetelwe kwi-100%. Bona 2 Table ...
Umzobo 2. 

Ukubala kwe-c-Fos immunopositive-cell in kwimimandla ye-hypothalamic ye-PR eyenziwa ngamagundane ngokuhambelana nolawulo lwe-PR (*P <0.05). Ukubalwa kweseli kulawulo lwe-PR kusetelwe kwi-100%. Yabona 2 Table Idatha eluhlaza. Idatha ibonakaliswa njengeendlela ± SE.

I-c-Fos expression ibonwe kweminye imimandla ye-CNS, kubandakanya i-amygdala kunye ne-cortex yecergus (Ikhiwane. 3). Nangona kunjalo, intetho yaqwalaselwa kwiimeko zombini zolawulo kunye nokunxulumana nemisebenzi ye-PR kunye ne-FR, iphakamisa ukuba imiba engathandekiyo yenkqubo (ukuphatha, ukuhambisa kwigumbi lenkqubo) isenokubangela ukuba kusebenze. Ukunyanzelwa kwezi ngingqi akuqhutywa. Kwangokunjalo, ukusebenza ngaphakathi kwengingqi yeengqondo ezingezizo i-nXII kwajongwa, kodwa kwenzeka ngokudibeneyo kunye nolawulo kunye nemeko ezinxulumene nomsebenzi, kucetyiswa nendima ekuvuseleleni ngokungasebenzi okanye ekuziphatheni.

Umzobo 3. 

I-c-Fos yokugonywa kwi-pirform cortex (AP, −0.26 ukusuka kwi-bregma). Ugonyo lwabonwa kuwo omane la maqela ovavanyo (i-FR, PR, FRC, ne-PRC). Ubukhulu be-20 ×.

Sivavanye unxibelelwano phakathi kwe-c-Fos expression kwimimandla eyahlukeneyo ye-CNS. Ukudibanisa idatha kumaqela acinezelayo, sifumene unxibelelwano olubi phakathi kwe-c-Fos expression kwi-LH kunye ne-VMH; Ke, ukwenziwa kwe-VMH kunxulunyaniswa nokwehla kokusebenza kwe-LH (Pearson's R, −0.7986; t = −3.7534; P = 0.0056). Kwakhona, siqwalasele unxibelelwano oluqinisekileyo phakathi konxibelelwano lwe-c-Fos kwingingqi ye-LH kunye ne-VTA (Pearson's R, 0.7772; t = 3.493; P = 0.0082), ehambelana nokunxibelelana okwaziwayo kwe-monosynaptic phakathi kwale mimandla mibini (bona ingxoxo kwii-Ref. kwaye ). Sifumene unxibelelwano olubi phakathi konxibelelwano lwe-c-Fos kwi-VTA ngokuchasene ne-NAc-shell, nokuba kuvavanywa ngokwahlukeneyo ukusebenza kwe-FR (Pearson's R, −0.9262; t = −4.9125; P = 0.008) okanye ngentsebenzo ye-PR (Pearson's R, −0.9897; t = −9.7624; P = 0.0103), iyahambelana negalelo lokubuyisela eliphindaphindwayo phakathi kwemimandla enomhlaba oya kwi -antianti nigra kunye neVTA (, ). Sivavanye unxibelelwano phakathi kwe-c-Fos expression kwimimandla eyahlukeneyo ye-CNS, kunye nokuziphatha. Ukudibanisa idatha kumaqela acinezelayo, siqwalasele unxibelelwano oluchanekileyo phakathi kwe-c-Fos kwi-ARC, kunye noomatshini bokushicilela abasebenzayo (i-Pearson's R, 0.8208; t = 3.8017; P = 0.0067).

Ukuchongwa kwee-neurons ezenziwa ngokutya kwe-sucrose kunye nokukhuthaza i-sucrose.

Kwi-stem yengqondo, ii-neurons ze-c-Fos-positive azibonisanga kugonyelwa i-TH, umlinganiselo we-enzyme ye-epinephrine kunye ne-norepinephrine (kunye ne-dopamine); ke, ezi ze-catecholaminergic neurons azange zibonakale zenziwe yi-FR okanye imisebenzi ye-PR. Nangona kunjalo, ezinye i-c-Fos-positive neurons zabonisa ukugonyelwa okuqinisekileyo kwe-tryptophan hydroxylase, ebonisa ukuba inani le-serotonin neurons lenziwe lasebenza. Njengoko kubonisiwe kwi Ikhiwane. 4, kwi-ARC, imizimba yeeseli ye-c-Fos-eyayijikeleze i-AGRP egcinwe ziintsinga, kunye nephethini efanayo ye-NPY fiber / c-Fos kugonywa kwaqatshelwa (akuboniswanga). Kwi-PVN, ii-neurons ezi-c-Fos-positive zaye zavela zangqonge i-CRF-positive neurons, kodwa akukho colocalization yaqwalaselwa (idatha ayiboniswanga). Ikhiwane. 5 bonisa ugonyo lwe-orexin kunye neMCH kwi-LH. Ii-neuron ze-Orexin zifunyenwe kuzo zombini i-dLH kunye ne-peLH. Nangona sabona ii-neurons ze-MCH-positive kwi-peLH, ngokuqinisekileyo akukho colocalization nge-c-Fos kuloo mmandla we-LH. Nangona kunjalo, sabona i-c-Fos colocalization kwi-orexin-positive neurons ngaphakathi kwe-peLH (Ikhiwane. 6, umphezulu), kunye ne-c-Fos colocalization enomda kakhulu kwi-MCH kwi-VLH (Ikhiwane. 6, ezansi). Kufuneka iphinde icatshangelwe ukuba zombini ukwenziwa kwekhaya, kunye nokwenza i-colocalization nge-c-Fos, kungathathelwa ingqalelo ii-peptide neurotransmitters ezinje ngeCRH, kuba iigundane azange zenziwe ngaphambili nge-colchicine. Okokugqibela, ngaphakathi kwe-nucleus iqokelela ingqangi kunye neqokobhe (Ikhiwane. 7), i-c-Fos ihlangana kunye ne-GAD, i-enzyme yophando yokwenziwa kwe-Gaba ye-neurotransmitter, yaqwalaselwa, kuzo zombini i-FR kunye ne-PR yeerensi. Kwakukho indawo eqinileyo ye-T kwi-VTA; Nangona kunjalo, ii-neurons ze-c-Fos-positive ebezinqabile ukuba zibhekwe kwaye azibonakalanga zikhetha ukwahlula-hlula kunye ne-TH.

Umzobo 4. 

Ukuvalwa kwe-AGRP (luhlaza) kunye ne-c-Fos (ebomvu) kwiARC (AP −2.8) ye-PR-rat. Ubukhulu be-20 ×.
Umzobo 5. 

Ukuthintela ukungasebenzi kwe-orexin kunye neMCH kwi-LH. Ubukhulu be-20 ×.
Umzobo 6. 

I-c-Fos i-colocalization kumgangatho we-FR nge-orexin kwi-LF (AP −3.3) (umphezulu) kunye neMCH kwi-VLH (−AP-3.0) (ezansi). Ubukhulu be-X 40.
Umzobo 7. 

Ukunyanzeliswa kogonyo lokugonyelwa i-GAD (luhlaza) kunye ne-c-Fos (ebomvu) kwi-nucleus accumbens core (umphezulu) kunye negobolondo (ezansi).

UKUQALA

Kwisifundo esikhoyo, sisebenzise ukubonakalisa uhlobo lwento yokuqala yofuzo, c-Fos, ukuvavanya ipateni yokuqalwa kwe-CNS enxulumene nokuqalisa kokuziqhelanisa nomsebenzi wokucinezela we-lecrose, nokuba ngumsebenzi ongacacanga (FR) okanye umsebenzi qhubekeka nomsebenzi ocela umngeni ocinga ngokubonakalisa ukufuna komvuzo, njengokuzimela, kunye nokubandakanyeka ngokujikeleza kwe-limbic (, , ) (PR). Iipateni ze-Hypothalamic zokwenza kusebenze zahluke phakathi kwemisebenzi emibini, kunye ne-LH / i-limbic activation predoming in the FR task and medial hypothalamic / limbic activation predomin in the PR task (bona Ikhiwane. 1). Kukho izizathu ezahlukeneyo zoku. Okokuqala, ezi paradigms zinokuthi "imephu" ibe ngamava ahlukileyo kwi-CNS. Iigundane eziqeqeshelwe ukusebenza kwe-FR zingalindela umsebenzi olula, umvuzo omkhulu. Ulindelo lokutya okunomvuzo kufanele kube nefuthe elinamandla kwimodeli ye-c-Fos egcinwe kwiigundane ze-FR. Umahluko obonakalayo ofanelekileyo kwipatheni yokuvula ucebisa ukuba kungenzeka into yesibini-yokuba izilwanyana ze-PR zinamava ngakumbi nangomsebenzi-zincinci, kwaye oku kwaxhaswa ngumlinganiselo wethu we-c-Fos kwi-hypothalamus yeempuku ezifumene iiseshini ze20 FR , ebonise umsebenzi ofanayo kwiqela le-FR, hayi iqela le-PR. Zombini ezi zinto zinokwenzeka zinokuvavanywa ngokwanda ngokulandelelana kobunzima boqeqesho lwe-FR kunye nokuvavanya utshintsho kusebenzeyo lwe-CNS, kwimeko leyo, umntu unokuqikelela utshintsho olufanelekileyo kwimodeli yokuvula. Nangona kunjalo, ngelixa inani lamava oqeqesho elinokuthi lingaphenduli kwi-activation ye-CNS, umyinge wenani lemivuzo ebonakalayo kwiseshoni inokuthi: umsebenzi we-PR unokufundwa nje ngokuba ngamava "awaniki mvuzo kangako", kwaye oku kunokuba nokusebenzisana. ukungabikho kokusebenza kwe-LH. Ke, iphethini yokuvula ye-CNS ekuqaleni kweseshoni inokubonisa imeko yokuqonda, njengaleyo yendawo ene-paradigm: amandla e-activation ngaphakathi kwe-limbic circry ibotshelelwa ekufundeni nakwinkuthazo. Siqwalasele ukwahluka kwegama le-c-Fos kwi-medial hypothalamus yezilwanyana ze-FRC. Ngokukodwa ngaphakathi kwe-PVN, lo mahluko unokuba sisishwankathelo kwimigundwane ye-FR, ekuye kwajongwa kuyo umkhuba wokunyuka kwe-c-Fos vs. iigrigi ze-FRC (3 Table). Nangona kunjalo, kusebenze ngokubanzi i-medial hypothalamic activation ayifani phakathi kwezilwanyana ze-FR kunye ne-FRC.

Kumele kuqatshelwe ukuba nangona injongo yethu yayikuchonga iisayithi ze-CNS ezinegalelo ekuqaleni kwendlela yokuziphatha, ukulungiswa okwethutyana yinto ethile yokuqwalaselwa. Njengoko kuxoxwe ngezantsi, ngoku kuyabulelwa ukuba ii-subcompriers ezahlukileyo zendlela yokusebenza okanye yokusebenza okusebenzayo ziyanxulunyiswa ngokuvula inani labantu abahlukeneyo be-neurons (, , , ). Asinakho ukuyikhupha ngokupheleleyo into yokuba isebenze ngenxa yokucinezelwa ngokukhawuleza kwebhari okanye ukukhaba kwemivuzo kunokuba negalelo ngandlel 'ithile kwiipateni zokuvula esizibonileyo. Iziphumo zethu zinika isiseko sophando ngakumbi kwindima yeesayithi ezithile ze-CNS kwimicimbi eyahlukeneyo okanye izinto ezithile zomsebenzi wokuzilawula, kwaye kwezo zifundo, umlinganiso wezinye iintlobo zangoko ezinamacala aphambili avela "kwi" nakwi "off") iya kuba luncedo kakhulu.

Ukudityaniswa esikufumeneyo kwi-c-Fos expression phakathi kwemimandla eyahlukeneyo yobuchopho kuxhasa umsebenzi owaziwayo wokudibana kwe-hypothalamic kunye neendawo eziphambili ze-limbic zalo msebenzi wokufumana umvuzo, phakathi kwe-LH kunye ne-VMH, naphakathi komda we-Lonke kunye ne-VTA. (Jonga ingxoxo kwii-Ref. kwaye ). Sikwaphonononge unxibelelwano phakathi kwentetho ye-c-Fos kwimimandla eyahlukeneyo esebenzayo, kunye nokuziphatha. Ukudibana phakathi kwe-c-Fos kwi-ARC kunye nomatshini wokushicilela osebenzayo kuyahambelana nendima echazwe kakuhle yomsebenzi we-ARC kukutya ukutya (); ngokujonga kwethu kwangaphambili ukuba inaliti ye-insulin ngokuthe ngqo kwi-ARC yanciphisa ukuzilawula (); Ngeengxelo zangaphambili zendima ebaluleke kakhulu ye-ARC, kunye ne-endorphinergic neurons, ekufumaneni nasekusebenzeni kolawulo lwe-cocaine (-); kunye noqikelelo oluchongiweyo ukusuka kwi-ARC ukuya kwi-NAc (). Ke, i-ARC inokudlala indima ephambili kwindlela yokuziphatha ekhuthazayo yokufumana kunye nokufumana iintlobo ezininzi zokuvuselela okuvuza, kubandakanya, kodwa kungaphelelanga apho, ekutyeni. Okokugqibela, siqwalasele ukusebenza kwe-PVN kunye ne-VMH ngokuqala kokufuna kwe-PR. Oku kuyahambelana neendima ezichongwe kakuhle zezi medial hypothalamic nuclei kulawulo lokutya, ukunxibelelana ngokuthe ngqo kwe-synaptic kunye ne-ARC, kwaye kuchongwe unxibelelwano kunye ne-limbic circry (, , ).

Sifumene unxibelelwano olungalunganga olubalulekileyo phakathi kwentsingiselo ye-c-Fos kwi-VTA ngokuchaseneyo ne-NAc-shell, nokuba ihlolwe kwintsebenzo ye-FR okanye ye-PR. Yayimangalisa ngandlela ithile ukuba i-VTA isebenze kakuhle ayizange ijongwe kunxulumana ne-PR okanye i-FR sucrose-management (ngokuchasene nolawulo oluthile). Mhlawumbi oku kufumanisa kubonakalisa ixesha lokulinganisa kwethu, kugxile kwiindawo ezinokubakho ze-CNS ezisebenzayo ekuqaleni komsetyenzana, apho ezi zilwanyana beziqeqesheke kakuhle. Oku kuyahambelana nokuqatshelweyo kunye nengcinga ye-Schultz (), ukuba ukusebenza kwe-dopamine neuronal isebenze njengophawu lwesikhuthazo okanye imivuzo engalindelekanga, kwaye oku kusebenze kuncipha kunxulumana noqeqesho. Nangona kunjalo, ukukhutshwa kwe-striatal dopamine ngexesha lokuthatha i-sucrose kwizilwanyana eziqeqeshiweyo kubonakalisiwe kwenzeka njengesiqhelo esichanekileyo kwaye sesikhashana sedesti (). Ke ngoko, kunokwenzeka ukuba imeko esiyiqapheleyo ibaluleke kakhulu kunye neqela elikhulu lokufunda (okt amandla eenkcukacha-manani). Siqwalasele ukwenziwa kwe-NAc kumdibaniselwano kunye nokuthathwa kokubekwa kokuqala kwe-FR kunye ne-PR. Zombini ukusebenza kunye nothintelo lweeNeon neurons ziye zachazwa ngokunxulumana nentsebenzo yomvuzo, kwaye indlela yokusebenza / yokusebenza ixhomekeke kuqeqesho nakwimeko yokusingqongileyo, kwaye inxulumana nezinto ezahlukileyo zokuziphatha (umz. Ukujonga phambili, ukusondela, ukufunxa), , ). Njengoko kuchaziwe ngentla, umlinganiso we-c-Fos awuzukufaka into enjalo. ICarlezon iphakamise ukuba "umvuzo" unxulunyaniswa ikakhulu nokwehla komsebenzi we-NAc neurons, okt.). Oku akuhambelani nokubonayo kwethu-kuphuculwe kakhulu i-NAc c-Fos ngokuthelekiswa nolawulo lokuphatha kunye ne-c-Fos-positive neurons eyenziwe yodwa nge-GAD, engaguqukiyo nokwenza kusebenze kwe-kati spiny neurons (GABAergic) -kodwa thina asivavanyanga i-NAc neuronal "inhibition ". Ukusebenza kwe-NAc kunye nokuthintela kunokwenzeka kokubini ngexesha lemisebenzi, kunye nobuncinci be-anatomical kunye ne-tempority ezithile. Ngokombono wolu phononongo, umntu unokugqiba kwelokuba i-NAc iyabandakanyeka ekuthathweni kokuthatha isixhobo sokuzibulala, inqobo ye-NAc enegalelo ekusebenzeni kwezemoto kunye neqokobhe le-NAc elenza igalelo kwimisebenzi yomzimba kunye nakwinkuthazo yomsebenzi.

Sikwaphawule nokusebenza kwemimandla emibini ye-BNST (engaphandle nangasemva) kwiigundane ze-FR. I-BNST yinxalenye yokujikeleza kwe-limbic modulates iimpendulo ze-neuroendocrine kumava ophindaphindiweyo wevuselelo (, ), kwaye ngengqondo enkulu, inxulunyaniswa nokufunda malunga nokukhuthaza okuphindaphindiweyo. Nangona indima yayo icacisiwe ngokuthe gabalala ngokunxulumene namava oxinzelelo ophindaphindiweyo, ukufumanisa kwethu kubonisa indima ebanzi ye-BNST: I-BNST inokuguqula iimpendulo ze-CNS kwisimo esiphindaphindayo, kunye nokukhuthaza okungalunganga okanye koxinzelelo. Ukusukela oko sikubone kusebenze ekuqaleni kuka-FR, kodwa hayi i-PR, ukusebenza, ukuqeshwa kwe-BNST kunokuqhotyoshelwa kwimivuzo eyonyukayo yoqeqesho luka-FR. Ukujonga kwethu akukho kusebenze ngokuthe ngqo kwe-CRF neurons kuphakamisa ukuba ukuphendula okunamandla kwe-sucrose akuyona uxinzelelo olukhulu; Nangona kunjalo, intetho ye-c-Fos kwezinye ii-neuron ze-PVN iyahambelana nokujikeleza koxinzelelo lwe-circry (). Ngapha koko, u-Ulrich-Lai kunye noogxa baye baxela ukuba, usebenzisa indlela eyahlukileyo yokutya / yokondla i-paradigm, i-sucrose intake modulates umsebenzi we-PVN (). Okokugqibela, siqwalasele ukusebenza kwe-nucleus ye-hypoglossal nerve ngokunxulumana ne-PR kodwa hayi ukusebenza kwe-FR. Ukubaluleka koku kunokucingelwa kuphela; enye into enokwenzeka kukuba ukuhambelana kokhetho lwe-sucrose kungaphakanyiswa kwiigundane ezifaka imbuyekezo embalwa yomvuzo.

Ukufuna-kuphumelela kunye nokuthatha into ye-sucrose kufuneka kuthathelwe ingqalelo njengamava e-multimodality, eguquguqukayo ngexesha, njengoko ukungenisa kungakhokelela kwizibonakaliso zomda ezinxulumene nomxholo we-caloric we-sucrose, kunye nendawo yokuhlala kunye ne-alliesthesia yangaphakathi-yeseshoni.). Ngelixa uphando lwethu lujolise kwimpembelelo ye-endipine ye-endocrine signals, okt. I-insulin kunye ne-leptin, ukumodareyitha umvuzo wokutya, iziphumo zabo zinokuthi, emva koko, zixhamle ngokuthe ngqo kwinqanaba eliphakathi ngabathuthi kunye ne-neuropeptides edlala indima kwixesha elifutshane okanye elide. umvuzo wokondla okanye wokutya (bona ingxoxo kwi-Ref. ). Uphononongo lwangoku lubonelela ngengqondo ethile koku; Sibone kusebenze ii-neurons ezibonisa nokuba yi-MCH okanye i-orexin, ii-neuropeptides ezimbini ezi-orexigenic. Ezi ziphumo zinokuthi, enyanisweni, zingajongeli phantsi indima ye-MCH okanye i-orexin kumvuzo wokutya, njengoko i-immunocytochemistry kwiigundane ezingaphathwanga yi-colchicine ngokungathandabuzekiyo ibeka umda ekubonakaleni kwazo zombini ezi neuropeptides. Ukuchongwa kwee-neurons ezisebenza nge-orexin kwi-LH kuyahambelana ngokubanzi kwizifundo ezininzi ezibeka i-orexin neurons ekondleni, umvuzo wokutya, kunye nomvuzo wokuvuselela ngokubanzi ngokubanzi (umzekelo, 5, 7, 29). Siphawule ukusebenza kwe-peFLH orexin neurons. UAston-Jones noogxa bakhe () ndiyichasile indima yendima eyahlukileyo yabemi be-LH orexin neurons kwindlela yokuziphatha yomvuzo kwaye bane-neurons ye-peFLH orexin kwii-arousal, ngokuchasene nomvuzo ngeseti nganye. Ukufumana kwethu, ke, kuphakamisa indima ye-LH orexin kwinto yokuvuselela, kwaye mhlawumbi nokuziqhelanisa ne-lever esebenzayo okanye imikhondo yokuthatha ukuzimela.

Ifanelekile ukuba iqwalaselwe kwixesha elizayo bubunyani okanye ubume ngokubanzi be-sucrose njengesikhuthazo esinomvuzo. Nokuba ngaba ipateni yentshukumo yokuqala ye-CNS esiyixelayo apha yenzelwe ukutya njengokukhuthaza, okanye ngokubanzi ngokubanzi kolunye uxhaso olunomvuzo, iya kuhlala imisiwe. Njengoko kubhekiselwe apha ngasentla, ngakumbi kwimisebenzi ye-FR, ukumiliselwa kwenani lemivuzo ye-sucrose iya kulindeleka ukuba ibe neziphumo ze-metabolic, kunye nokuguqulwa kokukhutshwa kwehomoni (umzekelo, i-cholecystokinin, i-ghrelin, i-insulin) kunye neenguqu kwimisebenzi yokuqalisa kunye ne-CNS neural activation. Olutshintsho alunakulindeleka ukuba ludlale indima ngokuthe ngqo kwiipateni zokuqala ze-CNS esizilinganise kodwa zinokudlala indima ekufundeni ngomvuzo we-sucrose ngexesha loqeqesho. Kwakhona, ii-neuropeptides ezifana ne-orexin zinokuba nefuthe elibi kakhulu.

Isifundo sethu simele, kulwazi lwethu, ukubonakaliswa kokuqala kokusebenza kwe-medial hypothalamic nuclei ekuqaleni kokuqala kokuzibamba, kubandakanya zombini i-PVN, ebethelelwa kwi-homeostasis kunye nokuphendula koxinzelelo, kunye ne-ARC, ebaluleke kakhulu kwi-homeostasis yamandla, iimvakalelo zesondlo, kunye nokulawulwa kokutya. Ngokubalulekileyo, siqwalasele ukusebenza kwe-medial hypothalamus kunye ne-NAc, ngokunxulumana nokuqalwa kwe-PR, sicebisa ukuba zombini iindawo zasekhaya kunye nezinye iindawo ezinomzimba zidlala indima ekuqaliseni ukuzilawula. Iindawo ezongezelelekileyo zeesekethe ezijikelezayo zinokuphinda zifakwe kwindawo yexesha elizayo emsebenzini.

Iingcinga nokubaluleka kwazo

Ngelixa, ngokwembali, izifundo zokuqhubela phambili kunye nokuziphatha komvuzo zinokubangela kakhulu ukujikeleza kwe-CNS ye-limbic, ubungqina obuninzi buye bafumana obugxininisa ukusebenzisana ngokubalulekileyo phakathi kwe-limbic kunye ne-homeostasis ejikelezayo. Isifundo esikhoyo ngoku sicebisa ukubaluleka okunokubaluleka kwe-medial hypothalamic nuclei kumsebenzi oshukumisayo we-sucrose. Ukuthatha ngaphezulu kolu phononongo, izifundo ezizayo zinokuvavanya ukuba ingaba indima ye-medial hypothalamus iyimfuneko na nokuba ukusebenza kwayo kuyasebenza na ekufuneni eminye imivuzo efana neziyobisi zokuphathwa gadalala. Ukongeza, iziphumo zolu phononongo zibonelela ngesizathu sokufunda utshintsho lweendlela zokuziphatha ezishukumayo kwiimeko ezihambelana ne-medial hypothalamic physiology, efana nokutya kakhulu.

IZIKOLO

Olu phando luxhaswe ngamaZiko eSizwe wezeSibonelelo sezeMpilo kwi-DK40963. UGqr. Dianne Figlewicz Lattemann yiNzululwazi yeNkxaso kwiNzululwazi ePhakamileyo, yeNkqubo yokuPhanda ngeLobhu, iSebe leMicimbi yeVeterans Puget Sound Health Care, Seattle, Washington. UGqr Sipols uxhaswe liBhunga lezeNzululwazi leLatvia leNzululwazi ye-04.1116.

IZIXHOBO

Akukho kungqubana kwemidla, kwezemali okanye ngenye indlela, kubhengezwe ngababhali.

AMAKHODI

Siyabulela Drs. U-Yavin Shaham, uStephen Benoit, uChristine Turenius, kunye noJE Blevins ngengcebiso kunye neengxoxo eziluncedo.

IZALATHISO

1. Baskin DG, Figlewicz Lattemann D, Seeley RJ, Woods SC, Porte D, Jr, Schwartz MW. I-insulin kunye ne-leptin: Iimpawu ezihambelana neendlela ezimbini zokuthambekela kwingqondo ukulungiselela ukumiselwa kokutya kunye nobunzima bomzimba. Brain Res 848: 114-123, 1999 [PubMed]
2. I-Berthoud HR. Unxibelelwano phakathi kwengqondo "eyengqondo" kunye ne "metabolic" kulawulo lokutya. IPhysol Behav 91: 486-498, 2007 [PubMed]
3. UCarlezon WA, uThomas MJ. I-subctates yebhayoloji yomvuzo kunye nokuthintela: i-nucleus eqokelela umsebenzi we-hypothesis. I-Neuropharmacology 56 Suppl 1: 122-132, 2009 [Inkcazelo yamahhala ye-PMC] [PubMed]
4. UCarr KD. Ukondla, ukusetyenziswa kweziyobisi gwenxa, kunye nokuziva komvuzo ngesidingo se-metabolic. I-Neurochem Res 21: 1455-1467, 1996 [PubMed]
5. I-Cason AM, uSmith RJ, iTahsili-Fahadan P, iMoorman DE, iSartor GC, i-Aston-Jones G. Indima ye-orexin / i-hypocretin ekufuneni umvuzo kunye nokulutha: iimpembelelo zokutyeba kakhulu. IPhysol Behav 100: 419-428, 2010 [Inkcazelo yamahhala ye-PMC] [PubMed]
6. Utshintsho uJY, uSawyer SF, uLee RS, uWoodward DJ. Ubungqina be-electrophysiological kunye ne-pharmacological yendima ye-nucleus accumbens kulawulo lwe-cocaine ekuhambeni ngokukhululekileyo kwamagundwane. J Neurosci 14: 1224-1244, 1994 [PubMed]
7. Choi DL, Davis JF, Fitzgerald ME, Benoit SC. Indima ye-orexin-A kwinkuthazo yokutya, indlela yokuziphatha esekwe kumvuzo kunye nokuvuselelwa kokutya okubangelwa kukutya kwi-ronal. I-Neuroscience 167: 11-20, 2010 [PubMed]
8. I-Choi DL, i-Evanson NK, iFuray AR, i-Ulrich-Lai YM, i-Ostrander MM, uHerman JP. I-nucleus yebhedi ye-anteroventral ye-stria terminalis ngokungafaniyo ilawula iimpendulo ze-axothalamic-pituitary-adrenocortical axis kuxinzelelo olubi kunye nongapheliyo. I-Endocrinology 149: 818-826, 2008 [Inkcazelo yamahhala ye-PMC] [PubMed]
9. I-Choi DL, iFuray AR, i-Evanson NK, i-Ulrich-Lai YM, i-Nguyen MM, i-Ostrander MM, iHerman JP. Indima ye-posterior medial bed nucleus ye-stria terminalis ekumiselweni kwe-hypothalamic-pituitary-adrenocortical axis yokusabela kwi uxinzelelo olukhulu kunye nongapheliyo. I-Psychoneuroendocrinology 33: 659-669, 2008 [Inkcazelo yamahhala ye-PMC] [PubMed]
10. UDavis JF, Choi DL, Benoit SC. I-insulin, i-leptin, kunye nomvuzo. Iindlela eziLungisa iMetab 21: 68-74, 2010 [Inkcazelo yamahhala ye-PMC] [PubMed]
11. UDavis JF, uChoi DL, uSchurdak JD, uFitzgerald MF, uClegg DJ, Lipton JW, Figlewicz DP, Benoit SC. I-Leptin ilawula ukulingana kwamandla kunye nenkuthazo ngesenzo kwizijikelezo ezahlukeneyo ze-neural. Biol Psychiatr Kwicinezelo [Inkcazelo yamahhala ye-PMC] [PubMed]
12. U-Evans SB, uWilkinson CW, uBentson K, uGronbeck P, uZavosh A, uPinklewicz DP. Ukusebenza kwe-PVN kucinezelwe yi-hypoglycemia ephindaphindiweyo kodwa hayi i-corticosterone eyi-antecedent kwi-rat. Ngaba i-J J Physiol Regul integrated Comp Physiol 281: R1426-R1436, 2001 [PubMed]
13. Iintsimi HL, Hjelmstad GO, Margolis EB, Nicola SM. I-neurons yokwahlukanisa kwendawo ye-neurons kwindlela yokuziphatha efundwayo kunye nokuqiniswa okuqinisekileyo. U-Ann Rev Neurosci 30: 289-316, 2007 [PubMed]
14. I-Figlewicz DP, Benoit SB. I-insulin, i-leptin, kunye nomvuzo wokutya: Hlaziya i-2008. Ngaba i-J J Physiol Regul integrated Comp Physiol 296: R9-R19, 2009 [Inkcazelo yamahhala ye-PMC] [PubMed]
15. I-Figlewicz DP, uBennett JL, Aliakbari S, Zavosh A, Sipols AJ. I-insulin isebenza kwiindawo ezahlukileyo ze-CNS ukunciphisa i-sucrose intake kunye ne-sucrose yokuzilawula kumagundane. Ngaba i-J J Physiol Regul integrated Comp Physiol 295: R388-R394, 2008 [Inkcazelo yamahhala ye-PMC] [PubMed]
16. I-Figlewicz DP, iSipols AJ. Imiqondiso elawula amandla kunye nomvuzo wokutya. I-Pharm Biochem Behav 97: 15-24, 2010 [Inkcazelo yamahhala ye-PMC] [PubMed]
17. I-Finley JC, i-Lindstrom P, i-Petrusz P. I-Immunocytochemical localization ye-beta-endorphin-equkethe ii-neurons kwingqondo ye-rat. I-Neuroendocrinology 33: 28-42, 1981 [PubMed]
18. UFulton S, Woodwood B, Shizgal P. Ukuguquguqulwa kwengqondo komjikelo we-leptin. Isayensi 287: 125-128, 2000 [PubMed]
19. Iglasi MJ, uBillington CJ, uLeviine AS. I-Opioids kunye nokutya ukutya: ngaba iindlela ze-neural ezisebenzayo zasasazwa? I-Neuropeptides 33: 360-368, 1999 [PubMed]
20. Umlinganiselo weHodos W. Inkqubela phambili njengenyathelo lamandla omvuzo. Isayensi 134: 943-944, 1961 [PubMed]
21. IHommel JD, iTrinko R, iSears RM, iGeorgescu D, uLiu ZW, uGao XB, uThurmon JJ, uMarinelli M, uDiLeone RJ. I-Leptin receptor isayina kwi-midbrain dopamine neurons ilawula ukondla. I-Neuron 51: 801-810, 2006 [PubMed]
22. I-Ikemoto S. Dopamine yomvuzo wesekethe: Iinkqubo ezimbini zokuqikelela ukusuka kumbindi we-ventral ukuya kwi-nucleus accumbens-olfactory tubercle tata. I-Brain Res Rev 56: 27-78, 2007 [Inkcazelo yamahhala ye-PMC] [PubMed]
23. Ikemoto S, Panksepp J. Ukungafani phakathi kokuphendula kunye neempendulo zokunyanzeliswa ngokwenza iziyobisi kwimeknoloji yemimandla yobuchopho efanelekileyo. I-Behav Neurosci 110: 331-45, 1996 [PubMed]
24. Ikemoto S, RA olumkileyo. Imephu yeendawo ezinokubangela ukuba ufumane umvuzo. I-Neuropharmacology 47: 190-201, 2004 [PubMed]
25. Jiang T, Soussignan R, Rigaud D, Martin S, Royet JP, Brondel L, Schaal B. Alliesthesia kwimikhondo yokutya: heterogeneity over the stimuli and sensory modalities. IPhysol Behav 95: 464-470, 2008 [PubMed]
26. Kelley AE, Berridge KC. I-neuroscience yemivuzo yendalo: ukubaluleka kweziyobisi ezichasayo. J Neurosci 22: 3306-3311, 2002 [PubMed]
27. UKelley SP, Nannini MA, Bratt AM, Hodge CW. I-Neuropeptide-Y kwi-nucleus ye-patriometri yonyusa ukuzilawula kwe-ethanol. Iipeptides 22: 515-522, 2001 [Inkcazelo yamahhala ye-PMC] [PubMed]
28.UKim EM, uQuinn JG, uLevine AS, u-O'Hare E.Umkhombandlela we-opioid-opioid odibeneyo phakathi kwenucleus yeqokobhe le-accumbens kunye ne-nucleus esembindini ye-amygdala kumgangatho. Ubungqina beBrain Res 1029: 135-139, 2004 [PubMed]
29. Kotz CM. Umdibaniso wokondla kunye nokuzilolonga okwenziwa ngomzimba: indima ye-orexin. IPhysol Behav 88: 294-301, 2006 [PubMed]
30. I-Leinninger GM, uJo YH, uLeshan RL, uLouis GW, uYang H, uBarrera JG, uWilson H, u-Opland DM, uFaouzi MA, uGong Y, uJones JC, iRhode CJ, uChua S, uJr, uDiano S, uHorvath TL, uSeeley RJ, U-Becker JB, Münzberg H, Myers MG., Jr Leptin usebenza ngokusebenzisa i-leptin receptor-eveza i-hypothalamic neurons ye-postal yokuguqula inkqubo ye-mesolimbic dopamine kwaye acinezele ukondla. I-Cell Metab 10: 89-98, 2009 [Inkcazelo yamahhala ye-PMC] [PubMed]
31. U-Li D, u-Olszewski PK, uShi Q, uGrace MK, uBillington CJ, uKotz CM, uLevi AS. Iziphumo ze-opioid receptor ligands zifakwe kwi-rostral lateral hypothalamus kwi-c-Fos kunye nokuziphatha kokutya. Brain Res 1096: 120-124, 2006 [PubMed]
32. UMorton GJ, Blevins JE, Kim F, Matsen M, Nguyen HT, Figlewicz DP. Isenzo se-Leptin kwindawo yecandelo lokungena lomoya sinciphise ukufunxwa kokutya kusetyenziswa iindlela ezizimeleyo ze-IRS-PI3K kunye nokusayina kwe-MTOR. NdinguJ J Physiol Endocrinol Metab 297: ExNUMX-E202, 210 [Inkcazelo yamahhala ye-PMC] [PubMed]
33. UNicola SM, Yun IA, Wakabayashi KT, Fields HL. Ukudubula kwee-nucleus kuqokelela i-neurons ngexesha lesigaba sokukhuthaza somsebenzi wokunyusa umsebenzi wokuxhomekeka kuxhomekeke kumvuzo wangaphambili wokuqikelela. J Neurophysiol 91: 1866-1882, 2004 [PubMed]
34. I-Paxinos G, Watson C. I-Atlas ye-Rat Brain kwii-Stereotaxic Coordinates, i-5th ed San Diego, CA: Elsevier Academic Press, 2005
35. UPerello M, uSakata I, uBirnbaum S, uChuang JC, u-Osborne-Lawrence S, uRovinsky SA, u-Woloszyn Yanagisawa M, uLutter M, uZigman JM. I-Ghrelin yonyusa ixabiso elinomvuzo lokutya okunamafutha aphezulu ngendlela exhomekeke kwi-orexin. I-Biol Psychiatr 67: 880-886, 2010 [Inkcazelo yamahhala ye-PMC] [PubMed]
36. I-Petrovich GD, i-Holland ye-Holland, i-Gallagher M. Amygdalar kunye neendlela eziphambili zangaphambili kwi-hypothalamus yeconstic zenziwa yindawo efundileyo ekhuthaza ukutya. J Neurosci 25: 8295-8302, 2005 [PubMed]
37. UQuinn JG, u-O'Hare E, uLeviine AS, uKim EM. Ubungqina bokunxibelelana kwe-mu-opioid-opioid phakathi kwenucleus parventricular kunye ne-ventral tegmental ndawo kumgangatho. Ubungqina beBrain Res 991: 206-211, 2003 [PubMed]
38. IRichardson NR, iRoberts DC. Ukuhlengahlengiswa komyinge weeshedyuli kwizifundo zokuzilawula iziyobisi kwiigundane: indlela yokuvavanya ukuqiniswa kokusebenza kakuhle. Iindlela zeJ Neurosci 66: 1-11, 1996 [PubMed]
39. Roitman MF, Stuber GD, Phillips PE, Wightman RM, Carelli RM. I-Dopamine isebenza njengemodareyitha engxamisekileyo yokufuna ukutya. J Neurosci 24: 1265-1271, 2004 [PubMed]
40. I-Roth-Deri I, Meyian R, Yadid G. Isifo se-hypothalamic endorphinic lesiones sibonisa ukufunyanwa kwe-cocaine ngokwakho kulawulo kumqolo. I-Euro Neuropsychopharmacol 16: 25-32, 2006 [PubMed]
41. URoth-Deri I, uSchindler CJ, uYadid G. Indima ebalulekileyo ye-beta-endorphin kwindlela yokuziphatha efuna icocaine. I-Neuroreport 15: 519-521, 2004 [PubMed]
42. URoth-Deri I, Zangen A, Aleli M, Goelman RG, Peled G, Nakash R, Gispan-Herman I, Green T, Shaham Y, Yadid G. Isiphumo se-cocaine esihlangulwe kunye nokuzilawula ngokwaso kumanqanaba ebeta-endorphin yangaphandle. kwi-nucleus accumbens. J Neurochem 84: 930-938, 2003 [PubMed]
43. URudski JM, uBillington CJ, uLevine AS. Iziphumo zeNaloxone ekuphenduleni kokusebenza kuxhomekeke kwinqanaba lokuncitshiswa. Ikhemesti Biochem Behav 49: 377-383, 1994 [PubMed]
44. I-Schultz W. Ukufumana ngokusesikweni nge-dopamine kunye nomvuzo. I-Neuron 36: 241-263, 2002 [PubMed]
45. Sears RM, Liu RJ, Narayanan NS, Sharf R, Yeckel MF, Laubach M, Aghajanian GK, DiLeone RJ. Ukulawulwa kwenqanaba le-nucleus yokuqokelelwa kwehypothalamic neuropeptide melanin-ogxinayo i-hormone. J Neurosci 30: 8263-8273, 2010 [Inkcazelo yamahhala ye-PMC] [PubMed]
46. U-Ulrich-Lai YM, uHerman JP. Ummiselo we-neural of endocrine kunye neempendulo zoxinzelelo lwe-autonomic. Indalo Rev Neurosci 10: 397-409, 2009 [Inkcazelo yamahhala ye-PMC] [PubMed]
47. I-Ulrich-Lai YM, i-Ostrander MM, uHerman JP. Ukutsalwa kwe-axa ye-HPA kuncipha ngokuthathwa kwenqatha ye-sucrose: umvuzo ophindaphindiweyo ngokuchaseneyo nokusetyenziswa kwe-caloric. IPhysol Behav. Cinezela [Inkcazelo yamahhala ye-PMC] [PubMed]
48. Ulumkile RA. Intsholongwane engezantsi yomvuzo kunye nenkuthazo. J Comp Neurol 493: 115-121, 2005 [Inkcazelo yamahhala ye-PMC] [PubMed]
49. I-Zahm DS, Becker ML, Freiman AJ, Strauch S, DeGarmo B, Geisler S, Meredith GE, Marinelli M. Fos emva kokuzilawula yedwa kunye nokuphindaphindiweyo kwe-cocaine kunye ne-saline kwi-rat: ukugxininiswa kwangaphambili kwe-basal forebrain kunye nokubuyisela kwakhona ukubonakaliswa. I-Neuropsychopharm 35: 445-463, 2010 [Inkcazelo yamahhala ye-PMC] [PubMed]
50. I-Zanger A, i-Shalev U. Amanqanaba e-beta-endorphin ye-beta ayaphakanyiswa ngumvuzo wokukhuthaza ubuchopho kodwa ayanda ngokutshabalala. I-Euro J Neuroscience 17: 1067-1072, 2003 [PubMed]