Iingqungquthela ezingapheliyo zeNetonal eziMluthayo (2013)

Curr Opin Neurobiol. Umbhalo-ngqangi wombhali; ifumaneka kwi-PMC ngo-Agasti woku-1, ngo-2014.

PMCID: PMC3717294

I-NIHMSID: I-NIHMS449224

Inguqulelo yokugqibela yomhleli yeli nqaku iyafumaneka apha UCrr Opin Neurobiol

Bona amanye amanqaku ku-PMC Wisdom nqaku epapashwe.

Yiya e:

Abstract

Ngokusebenzisa amaza alandelelanayo e-neurochemical stimulation ebangelwa ziziyobisi, umlutha udibanisa iisekethe ze-neuronal zobuchopho ezilamla umvuzo, inkuthazo, ekungaguqukiyo kokuziphatha kunye nokuphazamiseka okukhulu kokuzibamba kunye nokunyanzeliswa kweziyobisi. Itekhnoloji yokucinga ngengqondo ivumele iingcali ze-neuro ukuba zenze imephu ye-neural landscape yokulutha kwingqondo yomntu kunye nokuqonda indlela amachiza ayitshintsha ngayo.

Iinkqubo zeesekethe

Iithiyori ezininzi ziye zabekwa phambili ukuchaza into yokuba likhoboka. Umzekelo, impulsivity engaqwalaselwanga [1] (ukusilela ekuthinteleni ukuqhuba ngokugqithisileyo), ukunqongophala komvuzo [2] (impendulo engacacanga ye-dopaminergic kwimivuzo yendalo), ukufunda kakubi [3] (inkuthazo ekhulayo yokuxela kwangaphambili kweyeza kunye nokusetyenziswa okungapheliyo), ukuvela kweenkqubo ezichasayo [4] (amandla eempembelelo ezimbi ezibangela ukurhoxa), ukwenza izigqibo ezinempazamo [5] (ukubala okungachanekanga ekulungiseleleni isenzo) okanye ukuzenzekela kweempendulo [6] (ukungaguquguquki kwemikhwa yokuvuselela-impendulo), zonke zibe yingqwalasela yophando olunzulu nolunemveliso. Inyani kukuba ukungasebenzi kwezi kunye nezinye iimodyuli ezininzi ezisebenzayo [5] kusenokwenzeka ukuba babe negalelo, ngokuthe ngqo okanye ngokungathanga ngqo, ekungakwazini komntu okhobokileyo ukucinezela isimilo esingafanelekanga phezu kwayo nje imiphumo yayo emibi. Ubungqina bucebisa ukuba izimilo eziqaphelekayo ezibonisa umlutha we-phenotype (ukusetyenziswa kweziyobisi okunyanzelekileyo, ukuzithiba okungakwaziyo kunye nokungaguquguquki kokuziphatha) kubonisa intsebenziswano engalungelelananga phakathi kothungelwano oluntsonkothileyo (olu hlobo lweesekethe ezisebenzayo) ezibandakanyeka kwiindlela zokuziphatha ezijoliswe kwinjongo. (Umzobo 1).

Ifayile yangaphandle ephethe umfanekiso, umzekeliso, njl njl igama le-nihms449224f1.jpg

Iseti elungeleleneyo yeemodyuli ezisebenzayo ezidityanisiweyo ziqinisekisa ukusetyenzwa kwemiqondiso emininzi kunye nekhuphisanayo, kubandakanya umvuzo, ulindelo, ukunyameka, inkuthazo, ukufunda ngexabiso, ixabiso leemvakalelo, ukungacaci, ukungquzulana, kunye nokuqonda okukhokelela ekuthathweni kwezigqibo kwaye ekugqibeleni amandla ethu okusebenzisa simahla. intando. Izinto ezininzi zangaphandle kunye nezangaphakathi (izinto ezibangela), ezisebenza kwiinkqubo ezahlukeneyo zomlamli (abalamli), zinokuphazamisa ibhalansi phakathi kwenkqubo yeesekethe ezijongene nokulungelelanisa iinjongo zokuziphatha ezihambelanayo.

Ii-perturbagens ezininzi zangaphandle (umzekelo, iziyobisi, ukutya, ungcakazo, isondo, imidlalo yevidiyo, ukutya okunekhalori ephezulu, uxinzelelo) zinokubeka le bhalansi (kubantu abasesichengeni) kunye nokuqalisa kunye nokuziphatha okukhobokisayo. Kwangelo xesha linye i-neural nodes ezithile kunye nothungelwano olunxulumene nazo, xa zingasebenzi (okwesibini ukuya kwimfuzo okanye intsilelo yophuhliso okanye ukusuka kwiziyobisi okanye okunye ukuvezwa kokusingqongileyo) kunokudodobalisa intsebenziswano phakathi kweesekethe zobuchopho kwandisa ukuba sesichengeni sokuphazamiseka kwengqondo, kubandakanya nokukhotyokiswa. Iindlela zemolekyuli ezibangela unxibelelwano olungafanelekanga phakathi kweenethiwekhi ze-neuronal ziquka utshintsho kwi-NMDA kunye ne-AMPA receptor-mediated glutamate signaling [7], ezingayi kuxutyushwa apha kodwa ziye zahlaziywa kwenye indawo [I-8]. I-neural nodes, iirelays kunye neepateni zoqhagamshelo ezishwankathelweyo kula macandelo alandelayo abonisa ukuqonda kwethu kwangoku (kunye nokukhula) kokujikeleza okuphantsi komlutha.

Inkqubo yeMesostriatocortical

Ukukwazi ukwenza imikhwa kuye kwaba namandla kunye namandla afanelekileyo kwindaleko. Ukuziphatha okunyanzelekileyo, njengokulutha, kunokubambelela xa i-neural circuitry imisela imikhwa eguqukayo [9[10]. Ukukwazi kweendlela ezithile zokuziphatha ukuba zendele nzulu, emva kokuphindaphinda ngokwaneleyo, kunceda ukuchaza zombini ubunzima bokucinezela (oko kukuthi, ukunyanzeliswa [11-13[14]). Ukuhlala kubonakala ngathi kugxininiswe ikakhulu kwiisekethe ze-mesostriatocortical "ezibuyisela ikhowudi" indlela yokuziphatha yezenzo eziphindaphindayo [14,15] kwinkqubo ekubhekiswa kuyo ngokufanelekileyo “njengechunking” yeengxelo zentshukumo [16 ••]. Imizobo ecwangcisiweyo-kumanqanaba e-anatomical kunye neesekethe- yeendlela eziphambili ze-frontocorticostriatal ezinegalelo ekuhlaleni okunxulumene nomvuzo zibonisiwe (Isazobe 2A kunye no-B). Ulungelelwaniso olubangelwa ngamachiza naphina kule sekethe ye-bidirectional, phakathi kwendawo ye-ventral tegmental (VTA) kunye ne-substantia nigra (SN), i-ventral kunye ne-dorsal striatum, i-thalamus, i-amygdala, i-hippocampus, i-subthalamic nucleus kunye ne-prefrontal cortex (PFC) inokubangela okanye ququzelela inkqubo yokulutha ngokuphazamisa ukufunda okusekwe kumvuzo ngokumodareyitha ukonwatyiswa kwe-neuronal yengingqi [17,18]. Kwinqanaba le-molecular, ukulungelelaniswa okunjalo kukubonakalisa utshintsho lweplastiki oluchaphazela kakhulu indlela i-DA kunye ne-glutamate neurotransmission ezidityaniswa ngayo, okuvumela ukuba i-synapses yomelezwe okanye ibe buthathaka ngenxa yonxibelelwano lwe-interneuronal. [19].

 Ifayile yangaphandle ephethe umfanekiso, umzekeliso, njl njl igama le-nihms449224f2.jpg  

I-Fronto-striatal circuitry ye-stimulus-responts habits. A. Ukumelwa kwe-anatomical ecwangcisiweyo yenkqubo ye-mesocorticolimbic dopamine ebuchotsheni bomntu, iqaqambisa izikhululo ezininzi eziphambili zokulungisa: Indawo ye-Ventral Tegmental (VTA) kunye ne-Substantia Nigra (SN), i-Nucleus Accumbens (NAc) kwi-ventral striatum, iThalamus kunye ne-Subthalamic Nuclei, kunye I-cortex yangaphambili, phakathi kwabanye. Ilungiswe ngemvume [15]. B. Ezine zeesekethe ze-cortical ze-frontostriatal ezibonakala zidlala indima enkulu ekusebenzeni kwe-executive kunye nolawulo lwe-inhibitory. DL: i-dorsolateral; I-DM: i-dorsomedial; VA: i-ventroanterior; VM: i-ventromedial; r: ekunene; I-IFG: i-gyrus yangaphambili engaphantsi; I-preSMA: indawo yemoto yangaphambili; I-STN: i-nucleus engaphantsi kwethalamic. Ilungiswe ngemvume [28].

Inkqubo ye-DA yeyona nto iphambili kwindlela ebonisa ubungangamsha, yiyo loo nto indima yayo yokumodareyitha kumvuzo kunye nokuxela kwangaphambili umvuzo (ulindelo, ukufunda okumiselweyo, inkuthazo (ukuqhuba), ukuphinda usebenze ngokweemvakalelo kunye nemisebenzi yesigqeba. I-VTA/SN kunye nokufika kwi-striatum kudlala indima ebalulekileyo ekufundeni kumava adlulileyo kunye nokucwangcisa iimpendulo ezifanelekileyo zokuziphatha. I-Nucleus Accumbens (NAc) ye-ventral striatum, kodwa nakwi-dorsal striatum, i-amygdala, i-hippocampus kunye ne-PFC [20] (Umzobo 2). Nangona singekaqondwa ngokupheleleyo, senze inkqubela phambili ebonakalayo ngokuphanda iinkqubo ezisisiseko.

Umzekelo omhle, kwinqanaba leemolekyuli, luqwalaselo lokuba iiklasi ezimbini eziphambili ze-medium spiny neurons (MSN) kwi-striatum zahluke kakhulu ngokweepateni zabo ze-DA zokubonisa: ii-MSNs kwindlela ye-striatonigral (ethe ngqo) ye-D1 receptors. (D1R), eqhuba ukomelela kwe-dendritic ephuculweyo kunye nokubonakaliswa kwe-glutamatergic, ngelixa ii-MSNs kwindlela ye-striatopallidal (engathanga ngqo) ye-D2 uhlobo lwe-receptors (D2R), ebonakala ngathi ilamla isiphumo esichaseneyo [I-21]. Lo mahluko uchaphazela iipateni ze-neurotransmission eziphembelela iindlela zokuziphatha zokulungisa umvuzo ngokwesiseko sokuba umvuzo olindelweyo ufunyenwe ngokwenene na (Umzobo 3). Ukufumana umvuzo weziyobisi, uphando lubonise ukuba ukungalingani phakathi kwe-D1R (iziyobisi ezixhomekeke kwiyeza) kunye ne-D2R (iziyobisi ezixhomekeke ekunciphiseni) izibonakaliso ziququzelela ukunyanzeliswa kweziyobisi [22,23]. Umzekelo, ulawulo lwabachasi abathintela ngokuthe ngqo (i-D1; SCH23390) okanye engathanga ngqo (D2; Sulpiride) indlela kwi-dorsomedial striatum ineziphumo ezichaseneyo kumsebenzi olinganisa isithintelo sokuziphatha, kunye nexesha langaphambili elinciphayo lokumisa iSiphawulo sokuphendula kodwa isiphumo esincinci kwimpendulo ye-Go, kwaye le yokugqibela inyusa zombini i-Stop Signal Reaction kunye ne-Go Trial Reaction amaxesha [24]. Ezi ziphumo zibonisa ukuba ukubonakaliswa okwahlukileyo kwee-receptors ze-DA kwi-dorsomedial striatum kwenza ukuba kuthintelwe indlela yokuziphatha elungeleleneyo ngaphandle kokusebenza kokuziphatha. Okubangel 'umdla kukuba, i-D1R inobudlelwane obuphantsi be-DA kwaye yiyo loo nto isebenzayo xa ibonakaliswe kunyuko olukhulu lwe-DA njengoko kwenzeka ngexesha lokunxila ngelixa i-D2R inobudlelwane obuphezulu kwaye yiyo loo nto ivuselelwe kungekuphela nje ngokunyuka okubukhali kwe-DA kodwa nangamanqanaba asezantsi ngokwentelekiso ahanjiswa ngamanqanaba e-tonic eDA. Ke, iziphumo zeziyobisi zinokuba nexesha elifutshane lesenzo kwi-D1R mediated signing kune-D2R signing, esandula ukuqinisekiswa kwiziphumo zecocaine kwi-striatal's MSN [23]. Uvuselelo lwe-D1R luyimfuneko kwimeko ebandakanya oko kubangelwa ngamachiza [25]. Iziphumo zokuvezwa ngokuphindaphindiweyo kweziyobisi kwiimodeli zezilwanyana zibandakanya ukubonakaliswa kwe-D1R ngelixa zombini uxwebhu lwezifundo zangaphambi kweklinikhi kunye nezonyango ziyancipha kwi-D2R yokubonisa [26,27]. Oku kukhokelela kwinto ebonakala ngathi kukungalingani phakathi kwendlela evuselelayo ye-D1R edibeneyo ye-striatocortical kunye ne-inhibitory ye-D2R ephakathi kwendlela engathanga ngqo. Eyesithathu, ebizwa ngokuba yi-hyperdirect pathway, nayo ichaziwe (ikwabonisiwe kwi Umzobo 2B), apho uqikelelo oluvuselelayo phakathi kwegyrus yangaphambili engaphantsi (IFG) kunye ne-subthalamic nuclei (ukusuka kwiindawo zecortical ezinxulumene nemoto ukuya kwiglobus pallidus) kubangela inhibition yethalamic ngesantya esikhawulezayo xa kuthelekiswa nendlela ethe ngqo okanye engathanga ngqo, kwaye iye yabandakanyeka ukukwazi ukucinezela isimilo emva kokuba siqalisiwe [28].

 
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Umzobo wesicwangciso solawulo lwe-dopaminergic ye-loops ekhuthazayo kunye nengalunganga kwi-dorsal striatum. A. Xa isenzo siphumela kwimeko engcono kune-eqikelelweyo, i-DA neurons ivutha i-spikes, enokuthi isebenze i-D1Rs kwi-neurons yendlela ethe ngqo kwaye iququzelele isenzo esikhawulezileyo kunye notshintsho lweplastiki ye-corticostriatal eyenza kube lula ukukhetha eso senzo kwixesha elizayo. B. Ngokwahlukileyo koko, xa isiphumo sesenzo sibi kakhulu kunokulindelekile, i-DA neurons iyathintelwa ekunciphiseni i-DA, enokuthi inqanda i-D2Rs ngendlela engangqalanga ye-neuron, ukucinezela isenzo esikhawulezileyo kunye nokuqiniswa kwe-corticostriatal synapses, ekhokelela ekucinezelweni kweso senzo. ngelixa elizayo. Ishicilelwe kwakhona ngemvume [101].

Ukuqonda ngcono amandla ebhayoloji kunye nokusingqongileyo abumba iisekethe ze-mesostriatocortical kubotshelelwa ukuguqulela kungenelelo olusebenzayo ngakumbi. Ngokomzekelo, uxinzelelo lukamama lubonakaliswe ukuba luchaphazela kakubi i-dendritic arborization kwi-NAc kunye nezakhiwo ze-prefrontocortical zomntwana okhulayo [I-29]. Kwangokunjalo abantwana abakhuliswe kumakhaya eenkedama babonisa unxibelelwano lwangaphambili olungaphuhliswanga [30 ••]. Ngenxa yesikhundla esisembindini se-NAc kwisekethe eguqulela igalelo elikhuthazayo ukusuka kwinkqubo ye-limbic ukuya kwindlela yokuziphatha ejolise kwiinjongo, kunye nokunxibelelana kwayo ne-PFC, eyimfuneko ekuzilawuleni, ezi ziphumo zinokunceda ukucacisa umanyano phakathi kobubi bokuqala. iziganeko, iindlela zokuphuhliswa kwengqondo, kunye nempilo yengqondo [31-33].

Ngokufanayo, ukuqonda kwethu ngcono iisekethe ze-mesostriatocortical kukwaqalisile ukukhanyisela kwinkqubo ye-neurobiological ephantsi kobudlelwane obuguqukileyo phakathi kweminyaka yobudala bokusetyenziswa kweziyobisi kunye nomngcipheko wokulutha [34]. Umzekelo, utshintsho olusuka kwimpembelelo ephambili ye-SN njengomthombo woqhagamshelo lwe-DA ukuya kwimimandla engaphantsi kunye ne-cortical ebuntwaneni / ekufikiseni ukuya kwimpembelelo edibeneyo ye-SN kunye ne-VTA ebuntwini obudala.I-35] isenokwenza eli xesha lotshintsho ukuba libe buthathaka ngakumbi kumngcipheko okhulayo wokusetyenziswa kweziyobisi kunye nezinye iziphazamiso zengqondo, eziqatshelwe kwangoko ebomini. Ukufunyanwa kwesi siphumo sokukhula kuphakamisa imibuzo ebalulekileyo yophando olutsha. Ngokomzekelo, ngaba olu nxibelelwano lunokuthi lutshintshe impembelelo yokulawula i-corticotropin ekhupha iprotheni ebophezelayo (CRF-BP), into emodulatory enokubangela iimpendulo ze-glutamatergic [36] ebandakanyeka ekubuyiselweni ekufuneni icocaine [37], kwaye oko kubonakaliswa kwi-VTA kodwa hayi kwi-SN [38]?

Limbic Hubs

Undoqo we-mesostriatocortical circuitry ochazwe ngasentla unxibelelana nezinye izakhiwo kwinkqubo ye-limbic enefuthe kwindlela yokuziphatha enxulumene nomvuzo ngokubonelela ngolwazi olunxulumene, phakathi kwezinye, i-valence yeemvakalelo, iinkumbulo ezigciniweyo, umsebenzi wesondo kunye ne-endocrine, ulawulo oluzimeleyo, ukungenelela, kunye ne-homeostasis yamandla. Apha ngezantsi, siqaqambisa eyona nto iphambili ekufunyenweyo yakutsha nje ngokunxulumene nokubandakanyeka kwezinye zezi ndawo kukuphazamiseka kokusetyenziswa kweziyobisi (SUDs).

Amygdala

I-amygdala ifaka ilahleko yokulahleka kwaye ifake imvakalelo kunye noloyiko kwinkqubo yokwenza izigqibo. Ikwabonakala isebenza ngekonsathi kunye ne-ventral striatum ukuze ithathele ingqalelo into engeyiyo ngokweemvakalelo. ngokuzithoba kodwa kakhulu ezifanelekileyo kumvuzo oxhomekeke kumsebenzi [39]. I-amygdala eyandisiweyo (i-nucleus ephakathi ye-amygdala, i-nucleus yebhedi ye-stria terminalis, kunye negobolondo le-NAc), ngokunyusa umqondiso nge-corticotropin-releasing factor (CRF) kunye ne-peptides ehlobene ne-CRF, ikwabandakanyeka kwiimpendulo zoxinzelelo kunye negalelo (kodwa bona kwakhona imeko ye-habenula, ngezantsi) ukuya kububanzi inkqubo yokungavuzwa [40 ••]. I-amygdala sisimodareyitha esinamandla sokuziphatha okukhobokisayo, ngakumbi ngexesha lokufukanyelwa kwexesha elide lokunqwenela iziyobisi [41]. I-basolateral amygdala (BLA) ifumana i-dopaminergic innervations kwi-VTA kwaye ivakalisa i-D1 kunye ne-D2 receptors, ezichaphazela ngokwahlukileyo ukumodareyitha kwe-NAc kunye nomsebenzi we-PFC yi-BLA. Ngokomzekelo, ulawulo lwe-intra-BLA lomchasi we-D1R lunokubangela ukukhululwa kwe-DA kwi-NAc ngelixa igxininise kwi-PFC yangaphakathi (mPFC) ngelixa umchasi we-D2R wayengenampembelelo kule mimandla [42]. Kuya kongezwa ukuba uhlobo lwee-receptors ze-D3 kumbindi we-amygdala nazo zidlala indima ekufukameni kokunqwenela i-cocaine [43 ••]. Akumangalisi ukuba kukho ubungqina obubonisa ukuba ukuvuselela ingqondo enzulu ye-amygdala kunokunceda kunyango lwezifo zengqondo ezahlukeneyo, kuquka umlutha [I-44].

Insula

Utshintsho ukusuka kwi-flexible, injongo ejoliswe kwi-reflexive, ukuziphatha okunyanzelekileyo kubonakala kukwaphenjelelwa kukufunda ngezixhobo njengoko kumodareyithwa ngamagalelo e-interoceptive kunye ne-exteroceptive. I-insula idlala indima enkulu ye-interoceptive ngokubona kunye nokudibanisa ulwazi malunga nemeko ye-physiological yangaphakathi (kwimeko yomsebenzi oqhubekayo) kwaye idlulisele kwi-anterior cingulate cortex (ACC), i-ventral striatum (VS), kunye ne-ventral medial PFC (vmPFC) ukuqalisa ukuziphatha okuziqhelanisayo [45]. Ngokuhambelana nendima yayo ekuvaleni utshintsho kwimeko yangaphakathi kunye nokuqonda kunye nokusebenza okuchaphazelayo, izifundo ze-neuroimaging zibonise ukuba i-insula ephakathi idlala indima ebalulekileyo ekunqweneleni ukutya, i-cocaine kunye necuba.46-48] kunye nendlela umntu aziphatha ngayo iimpawu zokuyeka iziyobisi. Ke, ukungasebenzi kakuhle kwe-insular kunxulunyaniswa nokunqwenela iziyobisi kumlutha [49], ingcamango exhaswa kukulula okubhaliweyo apho iintshayi eziye zafumana umonakalo kwi-insular zakwazi ukuyeka [50 ••], kunye nezifundo ezininzi zokucinga zabantu abakhobokileyo [51,52]. Unxulumano oluphawulweyo phakathi kotywala kunye ne-insular hypofunction [53[]54], inokuthi ichaze ngokusilela ekuzaziseni ngexesha lokunxila kunye nokusilela ukuqaphela imeko ye-pathological yokuba likhoboka lomntu okhobokileyo, okuye kwachazwa ngokwesiko ukukhanyela [55]. [55]. Ngapha koko, uninzi lwezifundo zokucinga zibonisa ukusebenza okwahlukileyo kwe-insula ngexesha lokunqwenela [56], ecetyiswe ukuba isebenze njenge-biomarker ukuqikelela ukubuyela kwakhona [57].

Ithalamus, i-subthalamic nucleus (STN), i-epithalamus

Ukusetyenziswa kakubi kweziyobisi okungapheliyo ekugqibeleni kuphazamisa unxibelelwano lwee-hubs ezibalulekileyo [58]. Umzekelo, abaxhaphazi be-cocaine, xa kuthelekiswa nolawulo, babonisa unxibelelwano olusezantsi olusebenzayo phakathi kwe-midbrain (indawo ye-SN kunye ne-VTA) kunye nethalamus, i-cerebellum, kunye ne-rostral ACC, enxulunyaniswa nokuncipha kokusebenza kwethalamus kunye ne-cerebellum kunye nokuphuculwa kokungasebenzi kwe-rostral ACC [59]. Ukusebenza kwezi hubs, kunye neethagethi zazo ezininzi, zinokuphazamiseka kungekhona nje ngokungapheliyo kodwa kunye nokuchayeka ngokukhawuleza kweziyobisi zokusetyenziswa kakubi: umzekelo, ukuxiliswa kotywala kunokubangela ukutshintshwa kwepetroli, ukusuka kwi-glucose ukuya kwi-acetate, kwi-thalamus, i-cerebellum kunye ne-acetate. i-occipital cortex kwaye olu tshintsho luququzelelwa nokubonakaliswa kotywala okungapheliyo [I-60]. Kwelinye icala, uphononongo lwakutsha nje lwabantu abali-15 abafuna unyango lwe-cocaine-amakhoboka afumanise ukuba iinyanga nje ze-6 zokuziyeka zinokuhlangula uninzi lomsebenzi ocuthiweyo we-neural kwi-midbrain (ebandakanya i-VTA / SN) kunye nethalamus (ebandakanya i-nucleus ephakathi), ethi yanciphisa i-cocaine yokufuna indlela yokuziphatha njengoko ifaniswe kumsebenzi wokukhetha igama leziyobisi [61 ••].

I-STN idlala indima ebalulekileyo ekudityanisweni kolwazi lwe-limbic kunye ne-associative ekulungiseleleni ukudluliselwa kwayo kwimimandla ye-cortical kunye ne-subcortical [62]. Ilawula isenzo semoto kwaye ibandakanyeka ekwenziweni kwezigqibo ngakumbi xa usenza izigqibo ezinzima zokhetho [63,64]. Izifundo ezininzi ziye zachaphazela i-STN kumlutha. Ingxelo enye, umzekelo, yafumanisa ukuba i-crosstalk eyomeleleyo phakathi kokulawulwa kwempembelelo kunye nokucutshungulwa kwengqondo okuphucula iziphumo zokusetyenziswa kweziyobisi kunye negalelo ekuthandeni ukufikisa kuxhomekeke kakhulu ekusebenzeni kwe-STN [65]. Ukuvuselela ingqondo enzulu ye-STN, esetyenziswa kunyango lwe-Parkinson [66] kwaye kunokuba luncedo kwi-OCD enzima [67] iye yavavanywa kwizifundo zangaphambi kweklinikhi ukunciphisa iimpendulo ezivuselelweyo kwi-cocaine-cues [68].

Isignali ye-DA evela kwi-VTA kunye ne-SN ibalulekile ekufundeni indlela yokuziphatha evela emvuzweni ngelixa inhibition ye-VTA DA ukusayinwa yi-habenula esecaleni yenza ukuba ukufunda kuphephe ukuziphatha xa umvuzo olindelekileyo ungenzeki [69] okanye xa kunikwa isivuseleli esichasayo okanye ingxelo embi [70]. Ke, i-habenula esecaleni kunye ne-amygdala/inkqubo yoxinzelelo inokuba yinxalenye yesiphaluka esichasene nomvuzo kwingqondo ekhuthaza indlela yokuziphatha. Oku kuyahambelana neziphumo zophononongo lwangaphambi kweklinikhi apho ukusebenza kwe-habenula esecaleni kubangele ukuphinda kulawuleke kwi-cocaine kunye ne-heroin [71,72]. Ingcinga yangoku ke ibeka ukuba ukusetyenziswa okungapheliyo kweziyobisi ezikhobokisayo kukhokelela kwi-habenular hyperactivity, ekhuthaza imeko yeemvakalelo engalunganga ngexesha lokuyeka iziyobisi [73].

Cerebellum

Izifundo eziguquguqukayo zikwabandakanya i-cerebellum, kunye ne-cerebellar vermis ngakumbi, ekukhobokeni. Ngokomzekelo, i-cerebellum, kunye ne-occipital cortex kunye ne-thalamus yenye yeendawo zobuchopho ezisebenza ngokukhawuleza ekuphenduleni i-intravenous methylphenidate [74 ••] kwaye, njengakwithalamus, umphumo kwi-vermis yandiswa kakhulu (~50%) nanini na i-methylphenidate ilindeleke ngabaxhaphazi be-cocaine, ebonisa ukubandakanyeka kwayo ekulindeni ukuqinisa iziyobisi [74 ••]. Ewe, ezinye izifundo zifumanise ukuba i-cocaine cues inokubangela ukuba kusebenze i-cerebellar vermis kubasebenzisi be-cocaine [75], kwaye ukusebenza kwevermis kwakunxulunyaniswa nokuyeka ukukhotyokiswa butywala [76]. Igalelo elinokubakho le-cerebellum kwinkqubo yokulutha likwacetyiswa ngezifundo zokucinga eziyichaphazela kwiinkqubo zokuqonda eziphantsi kokwenziwa kokuziphatha okujoliswe kuko kunye nokuthintelwa kwazo xa zibonwa njengezingalunganga [I-75].

Umxholo we-dopamine kwi-cerebellum uphantsi ngoko ubungathathwanga ngokwesiko njengenxalenye yesekethe emodareyithwe yi-DA [77]. Nangona kunjalo, i-primate cerebellar vermis (lobules II-III kunye ne-VIII-IX) ibonisa i-axonal dopamine transporter immunoreactivity, ethi, kunye nobukho bentelekelelo ye-VTA kwi-cerebellum icebisa ukuba i-midbrain ebuyelayo kwisekethe ye-cerebellum inokwenzeka [78]. Ukufaneleka kwe-VTA-cerebellar vermis unxibelelwano ekuqhubeni umvuzo ikwaxhaswa yi-fMRI yomntu ezimeleyo esekwe kuqwalaselo lwe-neural ehambelanayo kwi-VTA kunye ne-cerebellar vermis ngelixa ujonge ubuso besini esahlukileyo [79] kunye noqhagamshelwano oluqinileyo olusebenzayo phakathi kwe-VTA kunye ne-SV kunye ne-cerebellar vermis (i-Tomasi ne-Volkow, kwi-press).

Izahlulo zeFrontocortical

Uninzi lophando lokuqala lokulutha lugxile kwimimandla yengqondo ye-limbic ngenxa yendima yabo kumvuzo weziyobisi [80]. Nangona kunjalo, ukonyuswa kwe-DA okubangelwa ngamachiza, akuchazi ukuba likhoboka kuba kusenzeka kwizilwanyana ezinaïve kwaye ubukhulu bayo buyehla kumlutha [I-81]. Ngokwahlukileyo koko, izifundo zangaphambi kweklinikhi kunye nezonyango zityhila i-neuroadaptations kwi-PFC eyenziwe yasebenza ngokukodwa lichiza okanye iziyobisi kwikhoboka kodwa hayi kubantu abangakhobokiyo kwaye ngenxa yoko banokudlala indima ephambili kwi-phenotype yokulutha (uphononongo, bona [82]).

Kubantu abakhotyokiswe ziziyobisi, ukuncitshiswa kwe-D2R yokubulala, ebandakanyeka kwezinye izinto ezinganyanzelekanga nezinyanzelekileyo zokuziphatha [83], inxulunyaniswa nokuncipha komsebenzi wemimandla ye-PFC, kuquka i-orbitofrontal cortex (OFC), i-ACC, kunye ne-dorsolateral prefrontal cortex (DLPFC) [84-86]. Uphononongo lukwabonisile, ukwehla komsebenzi we-cortical yangaphambili ngexesha lokunxila kumachiza amaninzi okuxhatshazwa [87] ehlala emva kokuyeka ukusetyenziswa kweziyobisi kubaxhaphazi abangapheliyo [88]. Ngokwenene, ukuphazamiseka kweenkqubo ezininzi ze-frontocortical kuye kwabikwa kubasebenzisi beziyobisi ezingapheliyo (Itheyibhile I) (bona [13] kuphononongo). Ngokwendalo, ukujolisa kuthintelo olungaphambili kwiziyobisi kuye kwaba yigrail engcwele yezicwangciso zonyango zokuphucula ukuzeyisa [61] [89].

1 Table      

Iinkqubo ezinxulumene ne-prefrontal cortex eziphazamiseka kumlutha

Phakathi kwemimandla engaphambili echaphazelekayo kumlutha we-OFC, i-ACC, i-DLPFC kunye ne-gyrus yangaphambili engaphantsi (IFG; indawo ye-Brodmann 44) ivelele ngenxa yokuthatha inxaxheba kubungqina obucacileyo, ulawulo oluthintelayo / ukulawulwa kweemvakalelo, ukwenza izigqibo kunye nokuthintela ukuziphatha ngokulandelelana.Umzobo 2B). Kuye kwachazwa ukuba ukulawulwa kwabo okungafanelekanga nge-D2R-mediated striatal DA signing kwizifundo ezikhotyokisiweyo kunokuba sisiseko sexabiso lenkuthazo ephuculweyo yeziyobisi kunye nokulahleka kolawulo lokusela iziyobisi [90 ••]. Ngequbuliso, ukungasebenzi kakuhle okunxulumene noko kunokubangela iziyobisi ezithile zokuziphatha, njengokusetyenziswa kwe-intanethi ye-pathological [91] kunye nokutya okunyanzelekileyo kwezinye iintlobo zokutyeba [83]. Kuyathakazelisa, kunye nokuphindaphinda umxholo, abaphandi baye bafumana ubungqina beendima ezihlukeneyo ze-D1R kunye ne-D2R kwi-PFC. Ngokomzekelo, uphando lwangoku lwangaphambili lubonise ukuba i-pharmacologic blockade ye-mPFC D1R iyancipha; ngelixa i-D2R inyusa utyekelo lokhetho oluyingozi, ibonelela ngobungqina bendima engadityaniswayo kodwa ehambelanayo ye-mPFC i-DA receptors ekunokwenzeka ukuba idlale indima enkulu ekucwangciseni ibhalansi elungileyo efunekayo kulawulo lokuthintela, ukulibaziseka kwesaphulelo, kunye nokugweba [92].

Ukongeza, ngenxa yokuba ukonakala kwe-OFC kunye ne-ACC kunxulunyaniswa nokuziphatha okunyanzelekileyo kunye nokungxama, ukumodareyitha okungahambi kakuhle kwe-DA kwale mimandla kunokuba negalelo ekunyanzelweni nasekuthatheni iziyobisi ngokungxama okubonwa kumlutha [93]. Ngokucacileyo, ithowuni ephantsi ye-DA inokuba semngciphekweni okhoyo wokusetyenziswa kweziyobisi kwi-PFC, nangona inokwenzeka ukuba ibe mandundu ngokuncipha okuthe kratya kwi-D2R yokubulala okubangelwa kukusetyenziswa kweziyobisi okuphindaphindiweyo. Ewe, uphononongo olwenziwe kwizifundo ezithe, ngaphandle kwembali elungileyo yosapho (ingozi enkulu) yokusela utywala, yayingezozinxila, zatyhila ukufumaneka okuphezulu kwe-D2R ye-striatal yesiqhelo eyayanyaniswa nemetabolism eqhelekileyo kwi-OFC, ACC, kunye ne-DLPFC [I-94]. Oku kuphakamisa ukuba, kwezi zifundo zisemngciphekweni wobutywala, umsebenzi oqhelekileyo we-PFC wadityaniswa nokubonakaliswa kwe-striatal D2R, enokuthi yona ibakhusele ekusebenziseni kakubi utywala.

Kwakhona kucebise ngeendlela zembuyekezo ezinokuthi zikhuseleke kumalungu athile osapho olusemngciphekweni, uphononongo lwakutsha nje lwabantwana bakowenu abangavumelaniyo ngenxa yokuba likhoboka leziyobisi ezivuselelayo [95 ••] babonise iyantlukwano yobuchopho kwi-morphology ye-OFC yabo, ebincinci kakhulu kumntakwabo okhobokileyo kunolawulo, ngelixa kubantakwabo abangakhobokiyo i-OFC ayizange yahluke kuleyo yolawulo [96].

Iziphumo zonyango

Ukwandisa ukuqonda kwethu kwiinkqubo ze-neural ezichatshazelwa kukusetyenziswa kweziyobisi ezingapheliyo kunye neempembelelo zokumodareyitha ukuba iijini ezihambelana nophuhliso kunye namandla okusingqongileyo zinezi nkqubo ze-neuronal, ziya kuphucula ukukwazi kwethu ukuyila izicwangciso ezisebenzayo zokuthintela kunye nonyango lwe-SUD.

Kungakhathaliseki nokuba yintoni na okanye yeyiphi into ehambelana nokukhubazeka echazwe kolu hlaziyo ikhokelela okanye ilandele ukusetyenziswa kweziyobisi ezingapheliyo, ubungqina obudityanisiweyo bezinto ezininzi bubonisa ubukho beesekethe ezininzi ze-neuronal eziye zingasebenzi kakuhle ngokulutha kwaye ezinokujoliswa ngokuthe ngqo ngokusebenzisa i-pharmacological, ngokomzimba. , okanye iindlela zokuziphatha zokuzama kunye nokunciphisa, ukumisa, okanye ukubuyisela umva intsilelo ethile. Umzekelo, izifundo ze-MRI ezisebenzayo zibonisa ukuba i-methylphenidate yomlomo inokuwenza uqheleke umsebenzi kumacandelwana amabini amakhulu e-ACC (okt, i-caudal-dorsal kunye ne-rostroventromedial) kunye nokunciphisa impembelelo kubantu abakhotyokiswe yi-cocaine ngexesha lomsebenzi wokuqonda kwengqondo [I-97]. Ngokufanayo, ukuqonda ngcono iindawo eziphambili kwiisekethe eziphazanyiswe lumlutha kunika iithagethi ezinokubakho zokuphanda ixabiso le-transcranial magnetic stimulation (TMS) okanye ukuvuselela ingqondo enzulu (DBS) kwizigulana ezichasene nonyango [I-98]. Okokugqibela, ungenelelo olusekwe kubungqina bengqondo yengqondo luya lusebenza ngakumbi kwaye luyafumaneka kunyango lwee-SUDs, umkhwa onokuthi ukhawulezise umbulelo kuphuhliso kunye nokusasazwa kweendlela zenoveli eziphuculwe yitekhnoloji yedijithali, ebonakalayo, kunye neselfowuni [99], nangokuqonda kwethu okwandisiweyo kwengqondo yentlalo, eya kusivumela ukuba sisebenzise impembelelo enamandla yeemeko zentlalo ekumodareyitheni iisekethe ze-neuronal kunye nokuziphatha kwabantu [100].

Iimbalasane

  • Umlutha luphazamiseko lwe-spectrum oluphazamisa ibhalansi ngaphakathi kwenethiwekhi yeesekethe.
  • Ubukhoboka bubandakanya ukungasebenzi kakuhle okutshabalalisa iziseko zokuzeyisa.
  • Iisekethe zokulutha ziyadibana kunye neesekethe zezinye iziphazamiso zokutsalela umxhelo (umzekelo, ukutyeba kakhulu).
  • Ukuqondwa ngcono kwezi sekethe ngundoqo kuthintelo olungcono kunye nonyango.

Imihlathi

Iphepha elichazayo ukuba awusenanto oyifunayo: Le fayili yeFayile yombhalo wesandla ongabhalwanga owamkelwe ukushicilelwa. Njengenkonzo kumakhasimende ethu sinika le ngcaciso yokuqala kwincwadi yesandla. Umbhalo wesandla uza kufumana ukukopishwa, ukufakela, nokuphonononga ubungqina obunokubakho ngaphambi kokuba kukhutshwe kwifomu yayo yokugqibela. Nceda uqaphele ukuba ngexesha lokuveliswa kweeprogram ezinokuthi zifumaneke ezinokuthi ziphazamise umxholo, kunye nazo zonke izisemthethweni ezichasayo ezisetyenziswa kwiphephancwadi.

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