IINJONGO zeNeuroscience, 2017, 4(1): 52-70. doi: 10.3934 / Neuroscience.2017.1.52
Review
Mani Pavuluri
, 
, Kelley Volpe, Alexander Yuen
ISebe lezeNgqondo, kwiYunivesithi yase-Illinois eChicago, eU.SA
Ifunyenwe: 02 January 2017 , Yamkelwe: 10 April 2017 , Ipapashwe: 18 April 2017
1. intshayelelo
Imimandla yobuchopho ebandakanyeka kumvuzo kunye nokujikeleza ngokweemvakalelo ziyadibana kwaye zinxibelelana kwimisebenzi yemihla ngemihla [1]. Ke, kungokwemvelo ukuqikelela ukuba nakuphi na ukungasebenzi kakuhle kwimimandla yaso naliphi na isekethe kunokwenzeka ukuba kube nefuthe kwiisekethe zombini kwaye kube phantsi kokuphazamiseka kweemvakalelo kunye nokukhotyokiswa ziziyobisi. [2]. I-Nucleus accumbens (NAc) yenye yengingqi ephambili ebuchotsheni eyinxalenye yomvuzo kunye neenkqubo zeemvakalelo ezibandakanya imisebenzi enje ngenkuthazo, ukufunda okomeleza, ukufuna uyolo, ukusetyenzwa koloyiko okanye ukuvuselela amandla kunye nokuqalisa umsebenzi wemoto. Injongo yephepha langoku kukubonelela ngenkcazo enzulu kunye nesiseko yesakhiwo se-NAc, uqhagamshelwano, kunye nendima esebenzayo kwiingxaki zengqondo kunye nokusetyenziswa kakubi kweziyobisi. Le nkcazo inikezela ngeenkcazo ezinokubakho kwimibuzo yeklinikhi eqhelekileyo evelayo ngokumalunga nokufuna umvuzo, ukulawulwa kweemvakalelo, kunye nophuhliso lomntwana kunye nefuthe lokuvuselela okuhambelanayo. Ngokuphathelele oku kubalulekile ukuqonda ubume be-NAc, kumxholo weemvakalelo kunye nomvuzo we-neural circuitry. Oku kubandakanya i-neurochemicals efanelekileyo eyi-dopamine (DA), i-gamma-aminobutyric acid (GABA), i-glutamate (Glu), i-serotonin kunye ne-noradrenaline, kunye nomsebenzi ohambelana ne-neural ukuchaza ikhonkco elibalulekileyo phakathi kokuphazamiseka kweemvakalelo kunye nokusetyenziswa kakubi kweziyobisi. [3].
2. I-Neuroscience esisiseko ye-NAc
2.1. Uqhagamshelwano lwe-NAc
Unxibelelwano phakathi kweendawo ezahlukeneyo ze-prefrontal cortex, i-dorsal striatum, i-ventral striatum, i-pallidum, i-amygdala, i-insula, i-hippocampus kunye ne-hypothalamus iboniswe Umzobo 1. Njengoko kubonwe, i-NAc iboniswa kwifom ye-cartoon ukubonisa i-hedonic hotspot (i-orange) kwingingqi ye-rostral ejongene "nokuthanda" imivuzo esekelwe kwizifundo zezilwanyana. Iqokobhe le-NAc likwaqulethe i-caudal hedonic coldspot (blue) enoxanduva "lokungathandi". Ngokufanayo, ummandla we-orange oboniswe kwi-pallidum kwindawo ye-caudal uxanduva lwe-hedonic hot spot kunye nomsebenzi we-opioid, kunye nokunyanzeliswa kwi-rostral blue spot. I-amygdala inoxanduva "lokufuna", kwaye ukuvuselela i-hypothalamic kukhokelela ekunyuseni kokubili "ukuthanda" kunye "nokufuna". I-Dopamine (DA) kunye ne-glutamate (Glu) zikhuthaza i-neurotransmitters ngelixa i-gamma amino-butyric acid (GABA) inefuthe lokunciphisa umsebenzi. I-DA idluliselwa kwindawo ye-ventral tegmental (VTA) ukuya kwi-NAc kunye ne-ventral (Ⅴ) pallidum. I-DA ikwadluliselwa ngokuthe ngqo kwi-dorsal striatum ukusuka kwi-VTA. I-GABA idluliselwa kwi-NAc ukuya kwi-Ⅴ. pallidum, VTA, kunye ne-hypothalamus esecaleni. I-Orexin idluliselwa kwi-hypothalamus esecaleni ukuya kwi-Ⅴ. pallidum. I-Glu idluliselwa kwi-NAc ukusuka kwi-basolateral nucleus ye-amygdala, i-orbitofrontal cortex, kunye ne-hippocampus kwi-synchrony kunye "nokufuna", ukuxabisa, kunye neenkumbulo, ngokulandelanayo. Uqhagamshelo olomeleleyo lwe-NAc kwi-insula luphantsi kwemvakalelo ye-visceral yokuvusa kunye nokonwaba okuhambelana nokunyuka kwe-DA kunye nokuncipha kwe-GABAA.
Umzobo 1. I-Neuroscience eSisiseko: iNucleus Accumbens Connectivity.
Uqhagamshelwano phakathi kweendawo ezahlukeneyo ze-prefrontal cortex, i-dorsal striatum, i-ventral striatum, i-pallidum, i-amygdala, i-insula, i-hippocampus kunye ne-hypothalamus iboniswe kumbono we-sagittal. I-NAc iboniswa kwifom ye-cartoon ukubonisa i-hedonic hotspot (i-orange) kwingingqi ye-rostral ejongene "nokuthanda" imivuzo esekelwe kwizifundo zezilwanyana. Iqokobhe le-NAc likwaqulethe i-caudal hedonic coldspot (blue) enoxanduva "lokungathandi". Ngokufanayo, ummandla we-orange oboniswe kwi-pallidum kwindawo ye-caudal uxanduva lwe-hedonic hot spot kunye nomsebenzi we-opioid, kunye nokunyanzeliswa kwi-rostral blue spot. I-amygdala inoxanduva "lokufuna", kwaye ukuvuselela i-hypothalamic kukhokelela ekunyuseni kokubili "ukuthanda" kunye "nokufuna". I-Dopamine (DA) kunye ne-glutamate (Glu) zikhuthaza i-neurotransmitters ngelixa i-gamma amino-butyric acid (GABA) inefuthe lokunciphisa umsebenzi. I-DA idluliselwa kwindawo ye-ventral tegmental (VTA) ukuya kwi-NAc kunye ne-ventral (Ⅴ) pallidum. I-DA ikwadluliselwa ngokuthe ngqo kwi-dorsal striatum ukusuka kwi-VTA. I-GABA idluliselwa kwi-NAc ukuya kwi-Ⅴ. pallidum, VTA, kunye ne-hypothalamus esecaleni. I-Orexin idluliselwa kwi-hypothalamus esecaleni ukuya kwi-Ⅴ. pallidum. I-Glu idluliselwa kwi-NAc ukusuka kwi-basolateral nucleus ye-amygdala, i-orbitofrontal cortex, kunye ne-hippocampus kwi-synchrony kunye "nokufuna", ukuxabisa, kunye neenkumbulo, ngokulandelanayo. Uqhagamshelo olomeleleyo lwe-NAc kwi-insula luphantsi kwemvakalelo ye-visceral yokuvusa kunye nokonwaba okuhambelana nokunyuka kwe-DA kunye nokuncipha kwe-GABAA. Eli nani lihlengahlengiswe ngokuyinxenye ukusuka kuCastro et al., 2015, Frontiers kwiiNkqubo zeNuroscience. [63]
2.2. Ubume ngaphakathi kwe-NAc ye-ventral striatum
I-accumbens nucleus okanye i-nucleus accumbens septi (i-Latin ye-nucleus ekufuphi ne-septum) yinxalenye ye-basal ganglia, kwaye ibekwe phakathi kwe-caudate kunye ne-putamen ngaphandle komda othile ukusuka kwi-caudate okanye i-putamen. [4]. I-NAc kunye ne-olfactory tubercle kunye ziquka i-ventral striatum. Ingqukuva ngokumila kwaye umphezulu wayo usicaba. I-NAc inde kubude bayo be-rostro-caudal ngokumalunga nobude bayo be-dorso-ventral. Inamacandelo amabini—iqokobhe kunye nondoqo [5,6]. Amacandelo amabini e-NAc abelana ngoqhagamshelwano kwaye asebenze imisebenzi eyahlukileyo kunye neyongezelelweyo.
2.3. Imisebenzi eyongezelelweyo yeselula kunye nokwahlukana kwe-neurochemical phakathi kwegobolondo kunye nengundoqo
2.3.1. Iqokobhe le-NAc
Inxalenye yangaphandle (okt, iqokobhe) ye-NAc ifana ne-hammock kwi-ventral, amacala kunye naphakathi kwamacala ombindi. [7,8]. Iyingxenye ye-amygdala eyandisiweyo, kunye ne-amygdala ibekwe kwi-rostral kwi-shell, kwaye ithumela i-afferents kwi-amygdala ye-basolateral. Yindawo yotshintsho phakathi kwe-amygdala kunye ne-dorsal striatum. Iqokobhe likwathumela ii-afferents kwi-lateral hypothalamus [8].
IiNeurons kwiqokobhe ziquka i-medium spiny neurons (MSNs). Ziqulethe uhlobo lwe-D1 okanye uhlobo lwe-D2-uhlobo lwe-dopamine (DA) receptors [9,10]. Kwiqokobhe, malunga ne-40% yee-MSNs zivakalisa zombini iindidi ze-neurons. Ngaphaya koko, ezi neurons zinoxinzelelo olusezantsi lwe-dendritic spines kunye ne-branching encinci kunye namacandelo esiphelo xa kuthelekiswa nee-MSN ezingundoqo. Ukongeza, ii-serotonin receptors zifumaneka ikakhulu kwiqokobhe [11,12].
2.3.2. Undoqo we-NAc
I-Neurons kumbindi (okt, inxalenye yangaphakathi ye-NAc) iqulathe indawo exineneyo, iiseli zangaphandle ezinamagatsha aphezulu ezinokuba luhlobo lwe-D1 okanye i-D2-type dopamine receptors. [10]. Ezi seli zisebenza kwiglobus pallidus kunye ne-substantia nigra.
I-Enkephalin receptors, i-opioid receptors kunye ne-enkephalins njenge-ligand ejongene ne-nociception, kunye ne-GABAA receptors, ebophelela iamolekyu ze-GABA ukuvula iziteshi ze-chloride kunye nokwandisa i-chloride conductance ukuvimbela amandla amatsha ezenzo, zikho kakhulu kwisiseko. [13,14].
2.4. I-Neurotransmitters ephantsi komvuzo, uchulumanco kunye nokuhlala kwi-dopamine-motivation kunye nomsebenzi womvuzo
Zombini kwiqokobhe kunye nombindi, isenzo se-DA sikhulu kuneso sikwi-dorsal striatum [15]. I-NAc ibandakanyeka ngokuthe ngqo ekufumaneni impendulo yoloyiko ngokusebenzisa imeko yesixhobo apho izilwanyana zikhenkceza kumxholo we-aversive stimuli. [16,17,18]. Undoqo we-NAc wahlukile kwiqokobhe kuba ubandakanyeka ekufundeni ukuchonga iimpawu ze-aversive stimuli ukuze uziphephe, ujikelele kwi-temporally discre stimuli. Iqokobhe le-NAc liyaziwa ngokuchaza okanye umqondiso wamaxesha okhuseleko phakathi kwee-aversive cues [19,20]. Ke ngoko, xa i-stimuli yangaphandle ingacacanga okanye ingalindelekanga, i-NAc kunye nokusebenza kwayo okungafaniyo, inokunceda ekuphepheni nasekusondeleni kwinjongo ekujoliswe kuyo. Ke ngoko, izilonda, i-DA receptor antagonism kumbindi we-NAc, okanye ukuqhawula amagalelo ukusuka kwi-anterior cingulate cortex ukuya embindini, ukunciphisa indlela eya kwi-incentive stimuli. [21,22,23]. Oku kufunyaniswayo kuxhasa ingcamango yokuba ingundoqo idlala indima ephambili "yokufikelela emvuzweni". Ukuncediswa koku kufunyanisiweyo, iqokobhe le-NAc ngummandla ophambili onoxanduva lokucinezela izinto ezingabalulekanga, ezingavuziyo, kunye nengeniso encinci ukunceda "ukuhlala emsebenzini". Ubungqina bukhomba kwinto yokuba nasiphi na isilonda kwiqokobhe le-NAc sikhokelela kwindlela engathintelwanga kumvuzo ngokuqonda okuncinci. [24]. Kwakhona, ngelixa uxinaniso oluphezulu lwabathuthi lunika usetyenziso olukhulu lwe-DA kumbindi, i-serotonin eyenziwe ngamachiza kunye ne-DA antagonism (umzekelo, i-clozapine, unyango lwe-psychosis) ikhokelela kwimbuyekezo enkulu ye-DA kwiqokobhe. Ewe, iqokobhe ngowona mmandla uphambili wesenzo sokulwa ne-psychotic esekwe kumsebenzi ohambelanayo we-mRNA ngaphakathi kweqokobhe [25,26]. Ukuthanda, umlutha, ukuzonwabisa, kunye nokuziphatha kwengqondo kunxulunyaniswa namanqanaba aphezulu e-DA. Amanqanaba aphezulu e-amphetamine aya kwandisa i-DA ukuya kumanqanaba alinganayo kwindawo ye-extracellular yeqokobhe kunye nengundoqo [27]. Ukonyuka okunjalo kwe-DA ngenxa yolawulo lwe-psychostimulant yokuhoywa kwe-hyperactivity (ADHD) kunokukhokelela kulonwabo kunye ne-mania, ingqondo, okanye ukufuna iziyobisi kakhulu phakathi kwabantu abasesichengeni abatyekele kwezi zigulo. [28,29]. Ngelixa siyiqonda imeko yezonyango yezehlo ezinje, akukacaci ukuba yintoni eyenza amaqela angaphantsi kwabantu athambekele ekungazinzini nolawulo lweDA. Imbuyekezo engeyiyo yeziyobisi iyaziwa ngokunyusa i-DA, ngakumbi kwiqokobhe le-NAc, ekhokelela ekuhlaleni. [30,31]. Ngaphaya koko, isivuseleli esiphinda-phindiweyo seziyobisi kunye nokwanda okuhambelanayo kwe-DA kukhokelela kwindawo yokuhlala eyingozi ngakumbi kwabo bantu ngokubhekiselele kwimbuyekezo ephindaphindiweyo enxulumene neziyobisi kunye ne-DA spikes. [32]. Ithuba lokuba imbuyekezo enxulumene neziyobisi inokubangela i-DA spikes kunye nokuhlala inokuthi ichaze umxholo wokulutha komdlalo wevidiyo, ukuseka i-neural correlates yokulutha.
Ngapha koko, i-NAc sisakhiwo esiphambili kwinkuthazo, kulawulo lweemvakalelo kunye nolawulo lwempembelelo. Ngokubhekiselele kumvuzo wokufuna kunye nezigwebo ezinganyanzelekanga, zombini izifundo zesilonda se-NAc kwizilwanyana kunye nezifundo zokucinga ezisebenzayo ekungcakazeni ziye zachaphazela ukungahambi kakuhle kwe-ventral striatum njengoko kukhokelela kukhetho oluphazamisekileyo lwexeshana, ukuthatha umngcipheko, okanye ukuziphatha okunganyanzelekanga kwimisebenzi ebandakanya iinketho ezinomahluko onokwenzeka. . Ukunyanzeliswa kunokuba nezizathu ezininzi, kodwa i-NAc sesinye setshaneli esibandakanyeka kumvuzo kunye nolawulo lweemvakalelo. [33].
2.5. I-Dopamine kunye ne-glucocorticoid receptors-indima yolonwabo lwengqondo kunye ne-psychosis enokwenzeka
I-DA kunye ne-glucocorticoid receptors zikhona kwi-shell ye-NAc [34,35]. I-steroids egqithisileyo okanye i-DA kwi-NAc, ikhokelela kwi-psychosis. I-Glucocorticoid receptors iphucula ukukhutshwa kwe-DA kunye nomsebenzi ohambelana nawo [35,36], enokuthi ibangele i-psychosis. Ukongezelela, utshintsho lwe-epigenetic, olufana ne-DNA methylation ye-glucocorticoid receptor gene (NR3C1) ngenxa yeziganeko ezibuhlungu, zikhoyo ngokukodwa ebusheni. [37,38].
Ke ngoko, uxinzelelo, kunye nokunyuka kwe-dopamine okuhambelana nee-psychostimulants okanye iziyobisi zokuxhatshazwa, kunokunyusa ingqondo ngokusebenzisa iindlela ezinxibeleleneyo kwi-NAc. Ukongeza, i-NAc ifumana uqikelelo oluthe ngqo kwi-hippocampus kunye ne-basolateral amygdala. Xa kukho isilonda kwi-NAc kunye / okanye indlela ye-stria terminalis edibanisa ne-amygdala, i-glucocorticoid agonists ayikwazi ukuphucula kunye nokulungelelanisa ukuqinisa imemori. [39]. Ke ngoko, ukungahambi kakuhle kwe-dopamine ekhokelela kwi-psychosis okanye ubunzima bokuqala kunokukhokelela kwiingxaki zengqondo eziqhubekayo, ezifana nezo zinxulumene nenkumbulo.
2.6. I-GABA kunye ne-glutamate-moderate motoric excitability
2.6.1. GABA
Ukuba i-GABAA iphantsi kwi-NAc, ikhokelela ku-hyperactivity okanye u-excitability, kwaye umva kuyinyani kwi-hypoactivity. [12,40,41]. Oku kunokuba nexabiso le-pharmacological apho i-DA yenza ukuba i-hyperactivity incitshiswe yi-GABAA ngendlela yoqhagamshelwano lwe-NAc ukuya ku-Ⅴ. i-pallidum (okt, icandelo langaphandle leglobus pallidus ye-basal ganglia kwi-subcortex) echaphazela ukusebenza kweemoto [42]. Ngokusekwe kwindima ye-insula ekuqhubeni imvakalelo ye-visceral yokuvusa [43,44], uxhulumaniso oluqinileyo lwe-NAc kwi-insula inokuchaza ukuvuswa komzimba okuhambelana nokunyuka kwe-DA kunye nokuncipha kwe-GABAA okanye ngokuchaseneyo. [45,46]. Ii-receptors ze-GABAB zikwanqanda ukuhamba, kodwa zilawulwa yi-acetylcholine (ACh) [45,47].
2.6.2. Glutamate
Le neurotransmitter ine-parallel, kodwa isiphumo esichaseneyo, se-GABAA nge-NAc [48]. Kuye kwaboniswa ukuba umsebenzi we-locomotor okanye u-motor excitability ayixhomekeke kumsebenzi we-DA kuphela, kodwa isekelwe kumsebenzi we-NAc obandakanya i-GABA kunye ne-glutamate. [49,50]. Kutshanje kuboniswe ngezifundo zezilwanyana ukuba isigqibo semotori sokufikelela kumvuzo asiqalwanga kwi-NAc, kodwa siququzelelwa ngokusebenza kakuhle ekukhetheni isenzo semoto ngelixa sisondela kumvuzo. [51].
2.7. I-Acetylcholine (ACh) kunye nendima yayo kwinkqubo yomvuzo
I-Striatal muscarinic ACh interneurons iquka i-M1, i-M2, kunye ne-M4; I-M1 i-post-synaptic kunye ne-excitatory, ngelixa i-M2 kunye ne-M4 zi-pre-synaptic kunye ne-inhibitory. Ezi interneurons synapse kunye ne-GABA mediated spiny output neurons. I-NAc, engundoqo kwiimpembelelo kunye nokuziphatha okuvuzayo okukhokelela ekubeni likhoboka leziyobisi, iiprojekthi ze-ACh zemveliso ye-neurons kwi-Ⅴ. pallidium. Izifundo zangaphambi kweklinikhi zibonise ukuba i-ACh evela kwi-NAc ilamla ukuqinisa ngempembelelo yayo kumvuzo, kwi-satiation, kunye nokuphazamiseka, kunye nolawulo olungapheliyo lwe-cocaine lubonise utshintsho lwe-neuroadaptive kwi-NAc. I-ACh ibandakanyeka ngakumbi ekufumaneni imibutho enemiqathango kunye nokuziphatha kokufuna iziyobisi ngemiphumo yayo ekuvuseleleni nasekuqwalaseleni. Ukusetyenziswa kweziyobisi ixesha elide kuboniswe ukuba kubangele ukuguqulwa kwe-neuronal kwingqondo echaphazela inkqubo ye-ACh kunye nokuphazamisa imisebenzi yokulawula. Ngaloo ndlela, inokuba negalelo ekwenzeni izigqibo ezingalunganga ezibonisa olu luntu kwaye lunokwandisa umngcipheko wokuphinda ubuyele ngexesha lokubuyisela. [52]. Ukongeza kwi-interface yayo kunye ne-GABAB receptors ekuvimbeleni ukuhamba, i-ACh ikwanoxanduva lokuhlutha emva kokutya, kwaye amanqanaba ancitshisiweyo anxulunyaniswa ne-bulimia njengemijikelezo ye-feed-purge. [53]. Ke ngoko, i-ACh inendima ekumodareyitheni ngokungathanga ngqo isekethe yomvuzo.
2.8. Amandla anxibelelanayo omvuzo odibanayo kunye nemimandla yokujikeleza ngokweemvakalelo ebandakanya i-NAc: Isiseko solawulo lweemvakalelo kunye nokwakheka komkhwa.
Iziphazamiso ezibandakanya isimo sengqondo kunye nokusetyenziswa kakubi kweziyobisi zihlala zikho kunye. Izinto ezibonakala zibandakanyeka zibandakanya ezo zinxulumene nokusetyenzwa ngokugqithisileyo kwe-affective, inkuthazo, kunye nokuphazamiseka kokwenziwa kwezigqibo. Ukuqonda ukubunjwa komkhwa, kwinqanaba lokuqala liqala ngenkqubo yomvuzo imodus operandi. Imimandla ye-dorsal kunye ne-ventral ye-striatum isebenza ngendlela ehambelanayo. I-dorsal striatum isembindini wokufunda iimeko ezinokwenzeka zokuvuselela umvuzo, kunye nokuqinisa imeko yesixhobo. [54,55]. Ngamanye amagama, i-dorsal striatum ikhulisa ukhetho olunxulumene nomvuzo. Emva koko, yi-NAc kwi-ventral striatum enoxanduva lweziphumo ezilandelayo ezisekelwe kwingqikelelo. [56]. I-NAc iqikelela isiphumo esisekwe kwimpazamo kwaye ihlaziya ukuqikelelwa komvuzo okanye isohlwayo [57,58]. I-mesolimbic neurons yendawo ye-ventral tegmental (VTA) idibanisa i-DA kunye ne-substantia nigra ithumela i-DA kakhulu kwiqokobhe kunye nombindi we-NAc, ukuyivumela ukuba yenze imisebenzi yayo. [59,60]. Zimpawu ezingenayo ezivela kwi-lobe yangaphambili kunye ne-amygdala, emodareyithwe yi-DA, ethatha icala kwindlela yokuziphatha eya kumvuzo. [61,62]. Indlela yokukhangela yokukhangela iququzelelwa lunxibelelwano phakathi kwehippocampus kunye neqokobhe le-NAc, ngakumbi ukuba kukho ukungacaci kunye nokungabikho komkhombandlela ocacileyo womvuzo. [1].
Ukongeza, i-hypothalamus esecaleni, ebandakanyeka kwimisebenzi yokulawula (umzekelo, "iziko lokutya") lithumela imiqondiso nge-mesocorticolimbic projections kwi-NAc kunye ne-Ⅴ. pallidum [63]. Kubonakala ngathi i-NAc kunye ne-Ⅴ. I-pallidum isebenza njengeendawo ze-hedonic "zokuthanda" kunye nomsebenzi okhuthazayo "wokufuna" imivuzo [64,65]. Ii-opioids ze-mu kunye nee-receptors ze-DA kwiqokobhe le-NAc kunye ne-Ⅴ. pallidum isebenza ngokuthe ngqo "ekuthandeni" kunye "nokufuna" imisebenzi [66,67]. Amanqanaba e-DA kwi-NAc kunye ne-norepinephrine ekhutshwe kwi-locus coeruleus kwisiqu sobuchopho adlala indima ebalulekileyo ekukhotyokisweni, ngakumbi ekufuneni iziyobisi xa uvinjwa ichiza elihlala likhona. [68,69].
Ukongeza, i-dopaminergic neurons evela kwi-VTA engayifaki i-olfactory tubercle, inxalenye ye-striatum ecaleni kwe-NAc. [69], kwaye babandakanyeka ekulaleni iziphumo ezinomvuzo zeziyobisi ezifana ne-amphetamine ngokuvelisa ukuvuseleleka. Ke ngoko, ngelixa ukufundwa kokuqala kolonwabo kunye nezinto ezinokwenzeka ezihambelana nazo zenzeka nge-dorsal fronto-striatal circuitry, yinkqubo yomvuzo we-ventral ye-orbitofrontal cortex (OFC), i-striatum, kunye ne-pallidum egcina umjikelo wokuhlala. [70].
Ngapha koko, igalelo elivela kwi-glutamatergic neurons ye-amygdala, hippocampus, thalamus kunye ne-prefrontal cortex (PFC) ukuya kwi-NAc iququzelele ulungelelwaniso phakathi "kokuthanda" kunye "nokufuna" [71]. Ngokukodwa, uqikelelo lwe-glutametergic olusuka kwi-OFC kunye ne-ventromedial PFC ukuya kwiqokobhe le-NAc ziyaziwa ngokomeleza umvuzo wokufuna umvuzo. [72,73]. Ke ngoko, i-amygdala kunye ne-OFC inokujongwa njengokuhambisa "imfuno kunye nemfuno" okanye imeko echaseneyo "yokungafuni okanye ukuchasa". Yi-NAc ebeka ithoni yokubaluleka kwenkuthazo okanye uxabiso kwimeko yokondla okanye nawuphi na omnye umsebenzi owonwabisayo (okt, "ukuthanda" okanye "ukungathandi").
I-amygdala ithumela imiqondiso echaphazelekayo ehambelana nomnqweno weyeza [74,75]. Ihippocampus inoxanduva lokugcina iinkumbulo ezinxulumene nokusetyenziswa kweziyobisi kwixesha elidlulileyo kunye nolonwabo oluhambelanayo [75,76]. I-insula ibonelela ngenkalo yamava omzimba olonwabo kunye nemeko evuselelayo enxulumene nokuthatha ichiza [77]. Ixabiso elihambelanayo lomvuzo kunye nokuziphatha okukhokelwayo okuhambelana nesiphumo kumiselwa yi-OFC, zombini ngokunxulumene novuselelo oluvuzayo okanye, kwimeko yokuthotywa kwexabiso lovuselelo, ukupheliswa kokufuna isimilo. [61].
Ngokubanzi, imveliso evela kwi-NAc ifikelela kwimimandla ye-basal ganglia, i-amygdala, i-hypothalamus kunye nemimandla ye-PFC. Ngokusekwe kwizifundo ze-neuroimaging ezibandakanya ulawulo olusempilweni (HC), izifundo eziphazamisekileyo ngokweemvakalelo, kunye nezifundo zokusetyenziswa gwenxa kweziyobisi, i-medial prefrontal cortex (MPFC), i-anterior cingulate cortex (ACC), i-ventrolateral prefrontal cortex (VLPFC) kunye ne-precuneus yavela njengee-hubs kumvuzo odibeneyo kunye iisekethe zeemvakalelo. Ukuziphatha okungxamisekileyo kunye nokunyanzeliswa kokufuna iziyobisi kumodareyithwa zombini ngokwendalo kunye nokukhuliswa. Imfuzo esemva kokuphazamiseka kulawulo lwempembelelo kunye nokulutha kusetyenziswa ukucacisa imeko yendalo, ngelixa izinto ezinempembelelo kokusingqongileyo (umzekelo, izithintelo zabazali okanye uxinzelelo loontanga ekusetyenzisweni kweziyobisi) zinokunciphisa okanye zandise ukuvezwa kwaye zibe negalelo elibonakalayo ekuqeqesheni umkhwa wokujikeleza.
3. I-Clinical Neuroscience ye-NAc
3.1. Indima yeNucleus Accumbens kumdaka oshushu wokuphazamiseka kweemvakalelo kunye nokuba likhoboka
Eyona ndlela iphambili yokuvula iboniswe kwi Umzobo 2. Oku kubonisa amaqela ezigulana kwingxaki nganye xa kuthelekiswa nolawulo olusempilweni kunye nemisebenzi evavanya nokuba ngumvuzo okanye i-emotion neural circuitry. Iintolo zibonisa ukwanda okanye ukuncipha kokusebenza kwimimandla ephambili yomvuzo kunye nokujikeleza kweemvakalelo ezidityaniswe ngokuntsonkothileyo. Kwimeko ye-bipolar disorder (BD), i-NAc ibonisa ukunyuka kokusebenza ekuphenduleni ukuvuselela iimvakalelo kunye nokunciphisa ukusebenza ekuphenduleni imivuzo, ipateni yokugqibela ifana naleyo ibonwa kwingxaki enkulu yokudakumba (MDD). Kwi-MDD, i-NAc ibonisa ukunciphisa ukusebenza kuzo zombini izivuseleli zeemvakalelo kunye nomvuzo, ngokuchasene noko kubonwe kukuphazamiseka kweziyobisi.
Umzobo 2. I-Clinical Neuroscience: Indima ye-Nucleus Accumbens kwi-Hot Mess ye-Emotion Dysregulation and Addiction.
Eyona ndlela ibalaseleyo yokuvula iboniswe kulo mzobo apho amaqela ezigulana kwindawo nganye yokuphazamiseka athelekiswe ngokuthe ngqo nolawulo olusempilweni kunye nemisebenzi evavanya umvuzo okanye i-emotional neural circuitry. Iintolo zimele ukonyuka okanye ukuncipha kokusebenza kwimimandla ephambili yomvuzo kunye nokujikeleza kweemvakalelo ezidityaniswe ngokuntsonkothileyo. Kwimeko ye-bipolar disorder, i-Nucleus Accumbens (NAc) ibonisa ukunyuka okusebenzayo ekuphenduleni ukuvuselela iimvakalelo kunye nokunciphisa ukusebenza ekuphenduleni imivuzo, ipateni yokugqibela ifana naleyo ibonwa kwingxaki enkulu yokudakumba (MDD). Kwi-MDD, i-NAc ibonisa ukunciphisa ukusebenza kuzo zombini izivuseleli zeemvakalelo kunye nomvuzo, ngokuchasene noko kubonwa kukuphazamiseka kweziyobisi. I-VLPFC: i-ventrolateral prefrontal cortex; I-MPFC: i-cortex yangaphambili ye-medial; I-AMG: i-amygdala; OFC: i-orbitofrontal cortex.
3.2. Ipatheni ye-Neural yokusebenza kwi-NAc ekusebenziseni kakubi iziyobisi kunye nokuphazamiseka kwengqondo: izifundo zokucinga zomntu zokuvuselela iimvakalelo kunye nomvuzo.
Uninzi lwezifundo zabantu ezandisa ulwazi ngendima ye-NAc zisekwe kwizifundo ze-fMRI ezivavanya umvuzo kunye/okanye ukujikeleza ngokweemvakalelo. Ngokumalunga ne-NAc, umbono ochanekileyo ufunyenwe njengemifanekiso ye-T2 kunye necandelo le-coronal apho lide kakhulu kwaye libonisa iinkcukacha ezininzi. [3]. Ipateni engaguqukiyo yokusebenza kwengqondo iye yavela ekuchongeni ukungasebenzi kakuhle kwe-circuitry interfacing kuyo yonke ingxaki. Ekutolikweni kwezi mvavanyo, zombini umsebenzi owandisiweyo kunye nokungabikho komsebenzi kufuneka kuthathelwe ingqalelo. Xa kukho uvuselelo lobunzulu obuphakathi, ummandla wobuchopho osebenza ngokuyinxenye nokuba wonakele, ubonisa ukusebenza okwandisiweyo. Ukuba lo mmandla wobuchopho uphononongwa ngovuselelo lokuqina okuqatha (kwaye kulamlwa luhlobo lwesidubedube apho iimbono zahlukile, njengezigulana ezine-bipolar disorder zisabela kubuso obunomsindo ngaphezu kobuso oboyikayo), loo nto ayibonisi kuvula okanye inciphise isalamane sokwenza kusebenze. kubemi abasempilweni. Le nto iye yaqatshelwa ngovavanyo olunyamekileyo lweepatheni kwizifundo ezininzi ukwenza ingqiqo yokuhluka ekusebenzeni kwengqondo ekuphenduleni kwiiprobes ezahlukeneyo.
3.2.1. Ingxaki enkulu yokudakumba (MDD)
Ngokumalunga ne-HC, abantu abane-MDD babonise ukuncipha kokusebenza kwi-NAc ekuphenduleni nasiphi na isivuseleli esivuzayo, kodwa okongeziweyo kokusebenza ukuze kuchaphazeleke ngokweemvakalelo (umzekelo, ukusetyenzwa kobuso obufihlakeleyo okanye isizukulwana sokuqonda sempembelelo entle) [78]. Ngamanye amazwi, kwi-MDD, i-NAc ayisebenzi kakuhle ngomvuzo kwaye oku kunokuchaza ukuba kutheni le ndawo ibonakala idinga umvuzo omkhulu ukuze ifikelele kwinqanaba elifanayo lokusebenzisa njenge-HC (okt, "ayiyonwabisi ngokulula") Enye inkcazo ye-physiological kukuba Isivuseleli somvuzo sinokusebenza njengezinto ezibangela iimvakalelo ezicacileyo kuxinzelelo, kunye nefuthe eliphantsi ekusebenziseni i-NAc. Ke ngoko, inokuba yinto eyenzeka ngengozi okanye engacacanga ngokweemvakalelo ivuselela ukuphinda kusebenze ngokugqithisileyo kwi-NAc. Ngokuhambelana nomsebenzi we-NAc, i-amygdala ikwabonisa ukwanda kokusebenza kwizigulane ze-MDD, ngokumalunga ne-HC, ekuphenduleni ukuvuselela iimvakalelo ezingathandekiyo okanye ezicacileyo. [79]. Imimandla eyahlukeneyo yangaphambili ibonisa iipateni eziguquguqukayo zokonyuka okanye ukunciphisa ukusebenza, ngokungafaniyo nepateni engaguqukiyo ephawulwe kwiindawo ezingaphantsi. [80,81]. Ngaphakathi kwamava ethu eklinikhi ukusetyenziswa ngokugqithisileyo kwezinto kubonakala kunenjongo yokunyanga ngokwakho ukoyisa iimeko zeemvakalelo ezingalunganga ezinxulumene nomda othotyiweyo wokuphinda uphinde usebenze kwizinto ezimbi ezibangelayo. Oku kuhambelana nemifuniselo yefiziyoloji esiyishwankatheleyo.
3.2.2. Ukuphazamiseka kweBipolar (BD)
Ukuphendula umsebenzi wokuvuza kwaye nokuba kusetyenziswe kakubi iziyobisi, xa kuthelekiswa nezigulana ze-HC ezine-BD zibonisa ukusebenza okuphantsi kwe-VLPFC kunye nokwandisa ukusebenza kwe-amygdala yeemvakalelo ezicacileyo okanye ezicacileyo ezingalunganga, ukongeza kwimbuyekezo yokusebenza kwe-ACC. [82]. Uqwalaselo olunika umdla kukuba i-NAc iziphatha ngendlela kanye njengeVLPFC; ukusetyenzwa kwefuthe elibi okufihlakeleyo kukhokelela ekucuthekeni okucuthiweyo, ngelixa zombini ezicacileyo kunye nobuso obucacileyo obonwabileyo okanye obunoloyiko bukhokelela ekwandeni kokusebenza. [83]. Enye ingongoma ephawulekayo kukuba, kwi-BD, iimvakalelo ezidabukisayo okanye ezinomsindo zivame ukuba zichaneke ngokuthe ngqo kunoloyiko njengento ephazamisayo yeemvakalelo, enokuthi ichaze ukunyuka kokuvuselela okuhambelana noloyiko. Ke ngoko, xa imisebenzi yeemvakalelo isetyenziselwa ukwenza isekethe yeemvakalelo, ubunzulu bemisebenzi bubonakala bubangela ukungasebenzi kakuhle kokungasebenzi kakuhle kwi-VLPFC yezifundo ze-BD ngokunxulumene neHC. Oku kunika inkangeleko, ukuba i-VLPFC "iyanikezela" ekuphenduleni iimvakalelo ezimbi okanye ezinzulu.
Ukuphendula kulindelo lomvuzo, i-NAc ibonise ukunciphisa ukusebenza ngokuphendula kumvuzo wemali kwizifundo ze-BD ezihambelana neHC. [84]. Le yipateni efana naleyo ibonwe kwi-MDD, iphakamisa imfuno yomvuzo omkhulu wokufumana impembelelo yeemvakalelo efanayo naleyo ye-HC. Ke ngoko, ipateni ye-BD yahlukile kwi-MDD ekuphenduleni uchuku ngokweemvakalelo esekwe kumahluko we-pathophysiological, nangona ikhokelela kwimpendulo efanayo yokuziphatha kwi-stimuli yomvuzo.
Kwingcaciso malunga nokuba yintoni enokuthi ibe phantsi kweemeko zeklinikhi kwi-BD, iziphumo zefiziyoloji zovavanyo lwe-neuroimaging luxhasa ulwazi oluvela kwizifundo zezilwanyana. Kule nkalo, kunokwenzeka ukuba ukwanda komsebenzi we-amygdala kwiiprojekthi ze-BD umlinganiselo othile wokuqina ohambelana nokuxhamla. Ukuncipha komsebenzi kwimimandla ye-VLPFC kunye ne-OFC kunokukhokelela ekuthinteleni, kunye nokulawula okungahambi kakuhle kwempembelelo, kwaye kubangele ulonwabo olugqithisileyo olunxulumene nokuthotywa kwePFC-ekuthathweni kwezigqibo. Ngokusekelwe kwizifundo zezilwanyana [85] kunye nezifundo ze-BD ze-neuroimaging [86], ukudibanisa phakathi kwe-amygdala kunye ne-NAc inokufaneleka ekugxininiseni "ukufuna" kunye "nokufana" ekufuneni imivuzo. Ke ngoko, indlela yokuziphatha ebukhali yokufuna umvuzo (umzekelo, ukuthenga kakhulu, ukusebenzisa iziyobisi, ukusebenzisa ukutya, okanye isondo) inokuba kungenxa yokungasebenzi kakuhle kweemvakalelo kunye nemivuzo.
3.2.3. Izigulo zokuSetyenziswa Gwenxa kweZiyobisi
Kwiziyobisi okanye ukuphazamiseka kokusetyenziswa gwenxa kweziyobisi, malunga ne-HC, umbono ongeyonyani okanye ocacileyo wento ehambelana nokunqwenela ikhokelela ekwandeni kokusebenza kwi-NAc. [87]. Oku kusisiseko senkuthazo ehambelana nokunyuka kokusebenza kwi-OFC, i-ACC, kunye ne-amygdala, imimandla edityaniswe nomvuzo kunye nokujikeleza ngokweemvakalelo. [87]. Le mimandla ibonakala iqhelekile kubo bonke abafuna umvuzo, kungakhathaliseki ukuba i-stimuli ingaba okanye ayizoziyobisi [88,89]. Ngelixa inkuthazo ekufuneni iinjongo ixhomekeke kwi-NAc kwi-ventral striatum, inguqu eqhubela phambili yokwenziwa komkhwa ibonakala ixhomekeke kwi-dorsal striatum. [90]. Oku kuhambelana ne-hypothesis "yokuthanda" apho ukuqwalaselwa kokuqala komvuzo kuhambelana nokusebenza kwe-NAc. Ukuphazamiseka kokusetyenziswa kweziyobisi, malunga ne-HC, ukuncipha kokusebenza kwe-NAc kwenzeka kwesi sigaba sokujonga, nokuba yeyiphi na ilahleko elandelayo okanye ukufumana umvuzo. [91]. Ukonyuka kokukhululwa kwe-DA kwi-anterior ventral striatum, kodwa hayi kwi-dorsal caudate, kuboniswe ukuba kunxibelelene kakuhle ne-hedonic, okanye "ukuthanda", impendulo kwi-dextroamphetamine. [92]. Ngokwenyani, amava achukumisayo afanelekileyo e-hedonic "ukuthanda" akulula ukuba ahlukane "ekufuneni" ichiza. [93]. Ngokuphathelele ukudakumba, ukufuna impendulo ye-hedonic yinkcazo enokwenzeka yokunyanga ngokwakho ngokusebenzisa kakubi iziyobisi. Ngokukwanjalo, usetyenziso olukhuthazayo kwi-subpopulation yabasebenzisi lunokuthi lubekwe phambili ngenxa yokufuna imbuyekezo egqithileyo ebangwa kukugqithisela kwe-dopamine.
3.2.4. Iimpembelelo zonyango ngokuvuselela ingqondo enzulu (DBS)
I-DBS ye-NAc ilingelwe unyango lwe-refractory obsessive-compulsive disorder apho ukunyanzeliswa kwakucingwa kufana nokunyanzeliswa kokufuna iziyobisi, ukunyanzeliswa kwemoto okuzenzekelayo njenge-Tourette syndrome, ukudakumba kunye nokusetyenziswa kakubi kweziyobisi kunye notywala. [94]. Zonke ezi nzame azikhange zifumane ziphumo zibambekayo kwisiphumo. Iimpawu zokudakumba ziye zancitshiswa malunga ne-40% kweli qela [94,95].
3.2.5. Impembelelo ye-placebo kubantu abasempilweni
Xa abantu abadala abanempilo banikwa umngeni wentlungu, i-DA kunye nomsebenzi we-opioid kwi-NAc yadibaniswa nokusebenza okubonakalayo kwe-placebo ngokusekelwe ekunciphiseni ukulinganiswa kweentlungu. [96]. Ngokufanayo nolindelo lokuvuza, oku kuxhasa ukubandakanyeka kwe-NAc ngolindelo lwempendulo eyakhayo.
4. Isishwankathelo kunye neziphetho
Ingxoxo engaphambili yayinenjongo yokubonelela ngohlalutyo olunzulu lwe-NAc ukuvumela izazinzulu kunye nabafundisi ukuba baqaphele imiba emininzi yokusebenza kwayo. Ngokumalunga ne-imaging esebenzayo, ukuchonga i-NAc kufuna uhlalutyo olucokisekileyo ngenxa yeendawo ezininzi, ezincinci ezikufutshane, ezifana neenxalenye ze-caudate kunye ne-putamen, ezinokuthi ziphosakele nge-NAc okanye ngokuchaseneyo. Ngaloo nto engqondweni, ukuma kwe-NAc kuthetha ukuba umbono ogqwesileyo ufezekisiwe kwicandelo le-coronal ekutolikeni iziphumo ze-neuroimaging. Ukongeza, ukuqonda kwendima ye-NAc kwindlela yenkqubo yeemvakalelo kunye nomvuzo wokujikeleza inika umbono obanzi wendima yayo ekusebenzeni kwengqondo. Iphepha langoku libonise iziphumo kwi-NAc kwizifundo zezilwanyana ezingabantu kunye nezingezona ezabantu, ngovavanyo lwezo ziphumo zihambelana nokuqonda kweklinikhi. Uncwadi lwenzululwazi olukhoyo lwezo zombini i-neuroscience esisiseko kunye neyonyango edityaniswe ne-acumen evela kulwazi lweklinikhi lulungelelanisa i-triad enamandla ekuguquleleni ukuqhubela phambili ukuqonda kwethu indima yokusebenza kwe-NAc, njengoko kubonisiwe ngethemba kulo mbhalo-ngqangi. Isishwankathelo, izinto eziphuma kwiklinikhi ze-neuroscience, apho i-NAc idlala indima ephambili, zezi zilandelayo:
1. I-NAc idlala indima ebalulekileyo ekutshintsheni i-DA, i-GABA kunye ne-glutamate ekumodareyitheni umvuzo kunye neenkqubo zeemvakalelo.
2. Iindima ezidityanisiweyo zondoqo we-NAc kunye neqokobhe libandakanya ukukhetha umvuzo kunye nokuphepha iziphazamiso, ngokulandelanayo.
3. I-NAc ibonisa ukunciphisa ukusebenza kokuvuza kubantu abane-MDD kunye ne-BD, ngokumalunga naloo HC, kwaye oku kunokuchaza ukungabikho kolonwabo ngomvuzo (ngokufana ne-anhedonia) kwi-MDD kunye nesidingo sokuphishekela ngokunyanisekileyo umvuzo kwi-BD.
4. Nangona i-NAc ibonisa ukwanda komsebenzi kuzo zonke iziphazamiso zokusetyenziswa kweziyobisi, ngokubhekiselele kwi-HC, izifundo zezilwanyana zibonisa ukunyuka okuhlangeneyo komsebenzi kwi-amygdala edibeneyo kunye ne-Ⅴ. pallidum. Ukulindela kunye nokukhetha umvuzo kunye nokubandakanyeka kwe-NAc kwizifundo zabantu kunye nokonwaba kwe-amygdala ukugxininisa umvuzo ofunwayo kwizifundo zezilwanyana, kunokwazisa kunye ukugcwala ngokweemvakalelo kwindlela yokuziphatha ekhobokisayo.
5. Kwakhona kunokwenzeka ukuba ukungakhathaleli kunye nokulawulwa kwempembelelo ehambelana ne-DA ephantsi okanye amanqanaba e-noradrenaline kunokukhokelela ekunyamezelweni kokuphazamiseka, kwaye mhlawumbi, ukufuna umvuzo njengenye indlela eyanelisayo. Kule meko, unyango olufanelekileyo kunye nee-psychostimulants zinokunqanda ukuqhelaniswa neziyobisi ezingekho mthethweni. Kubonakala ngathi ixesha lokufikisa lelona xesha lisemngciphekweni lokunyuka kwaso nasiphi na isigulo esinovakalelo lwe-glucocorticoid receptor kwi-NAc. Ngelixa kungekho zimpendulo ziqinisekileyo, le mibuzo ingaphendulwanga ibeka imingeni yophando kwikamva.
Ukugqubana kwemidla
Bonke ababhali babhengeza ukuba akukho kungqubana kwemidla ngokumalunga neli phepha.
Ucaphulo
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