imvelaphi
ISebe le-Neuroscience, iYunivesithi yasePittsburgh, ePittsburgh, PA 15260, eU.SA.
Abstract
Ulutsha ludla ngokuphendula ngokwahlukileyo kunabantu abadala kwiimeko ezifanayo ezikhuthazayo, ezinje ngonxibelelwano loontanga kunye nezivuseleli eziyonwabisayo. Ukucacisa umahluko wokwenziwa kwe-neural kulutsha olufikisayo kubalulekile ekuqondeni le nto, kunye neziseko zobuthathaka obunzulu bokuziphatha kunye nengqondo, njengokusebenzisa kakubi iziyobisi, ukuphazamiseka kweemvakalelo, kunye ne-schizophrenia. Sikholelwa ukuba utshintsho olunxulunyaniswa neminyaka kwindlela ekwenziwa ngayo izinto ezivuselelayo kwimimandla engundoqo yengqondo lunokuba sisiseko sokuqikelelwa kwangaphambili kunye nokuba semngciphekweni kokufikisa. Ngenxa yokuba ukuziphatha okukhuthazwayo kungumba ongundoqo, kubalulekile ukuba uthelekiso olunxulumene neminyaka yomsebenzi wobuchopho lwenziwe ngexesha leemeko ezikhuthazayo. Sithelekise umsebenzi weyunithi enye kunye nesakhono sentsimi yendawo kwi-nucleus accumbens (NAc) kunye ne-dorsal striatum (DS) yokufikisa kunye neempuku zabantu abadala ngexesha lomsebenzi wesixhobo esikhuthazwa ngumvuzo. Le mimandla ibandakanyeka ekufundeni okukhuthazwayo, ukusetyenzwa kwemivuzo, kunye nokukhetha isenzo. Sinika ingxelo yomahluko wokusebenza kwe-neural ofikisayo kwi-DS, ummandla onxulunyaniswa ngokubanzi nokufunda kunokulungiswa komvuzo kubantu abadala. Ngokukodwa, abantu abafikisayo, kodwa hayi abantu abadala, babenenani elikhulu lee-neuron kwi-DS esebenzayo ngokulindela umvuzo. Iipateni ezininzi zokuphendula ezifanayo zabonwa kwi-NAc yamaqela amabini obudala. Umahluko womsebenzi weyunithi enye ye-DS ufunyenwe ngaphandle kokuphazamiseka okufanayo kwintsimi yendawo. Olu phononongo lubonisa ukuba kulutsha, ummandla obandakanyeka kakhulu ekufundeni nasekuyilweni komkhwa uphendula kakhulu emvuzweni. Ke icebisa indlela yendlela imivuzo enokubumba ngayo indlela yokuziphatha kwabantu abafikisayo ngokwahlukileyo, kunye nokwanda kobuthathaka babo bokuphazamiseka okuchaphazelayo.
Ngexesha lokufikisa kukho inkitha yotshintsho lwe-neurodevelopmental lwenzeka (1) ezinokuchaphazela indlela iziganeko ezibalulekileyo, ezifana nezivuseleli ezivuzayo, ezenziwa ngayo. Olo tshintsho lwe-neural processing lunokuba sisiseko seendlela zokuziphatha eziqhelekileyo ezibonwa kulutsha kuzo zonke iintlobo zezilwanyana ezanyisayo, ezinjengokuthatha ingozi (1-5), kunye notyekelo olwandayo lokuphuhlisa ukuphazamiseka okufana nokulutha, ukudakumba, kunye ne-schizophrenia (6-8). Phambi kokuba siqonde i-neural substrate yobu buthathaka, kufuneka siqale sifunde ngakumbi malunga neepateni eziqhelekileyo zokusetyenzwa kwe-neural yobuchopho bokufikisa, xa sithelekisa kwaye sithelekiswe nezo zomntu omdala.
Ngokusisiseko yonke into yokuziphatha kunye nokuba sesichengeni kwengqondo yokufikisa ibonakala ngexesha leemeko ezikhuthazayo. Ngoko ke kubalulekile ukuthelekisa umsebenzi we-neural wolutsha kunye nolo lwabantu abadala ngexesha lokuziphatha okukhuthazwayo. Ukuziphatha okukhuthazwayo sisenzo esiququzelela uhlengahlengiso kubudlelwane bomzimba phakathi kwento ephilayo kunye nesivuseleli (umzekelo, ukuba nokwenzeka okanye ukusondela kumvuzo othile) (9). Iimeko ezinjalo zokuziphatha, nangona kunjalo, ziya kulwenza lube nzima uhlalutyo lomsebenzi we-neural: Sazi njani ukuba iyantlukwano ye-neural ayibonisi nje umahluko wokuziphatha phakathi kwamaqela amabini obudala? Ngaba umahluko kulungiso lwe-neural ngenxa nje yokuphazamiseka kokuziphatha, okanye ngaba kukho iyantlukwano esisiseko ngakumbi kwiindlela ulutsha olufikisayo oludibanisayo kunye nokwenza iziganeko ezibalulekileyo kwimeko yenkuthazo? Senze kwi-vivo iyunithi enye yokurekhoda i-electrophysiological ukuthelekisa umsebenzi we-neural wolutsha kunye nolo lwabantu abadala ngexesha leziganeko ezinzima xa indlela yokuziphatha yayingabonakali phakathi kwamaqela amabini (umzekelo, ukubuyiswa kokubuyisela emva kwexesha kwiiseshini zamva xa umsebenzi ufundwe kakuhle). Ekwenzeni oku sisebenzise ngokufanelekileyo "i-havioural clamp" eyasivumela ukuba sichonge iyantlukwano esisiseko enxulumene nobudala engazange ibhidaniswe yintsebenzo.
Nangona uninzi lwengqondo yokufikisa kusafuneka ihlolwe ngale ndlela, sigxile kwi-dorsal striatum (DS) kunye ne-nucleus accumbens (NAc) ngenxa yendima yabo ephambili ekuziphatheni okukhuthazwayo. Ngokudibeneyo, le mimandla yobuchopho ibandakanyeka ekufundeni ngokudibeneyo, ukwenza imikhwa, ukusetyenzwa komvuzo, kunye nolawulo oluguqukayo lweepatheni zokuziphatha (10-13). I-striatum ifumana uqikelelo oluvela kwimimandla ye-cortical ebandakanyeka kwiimvakalelo, iimoto, kunye neenkqubo zokuqonda (14), kunye negalelo le-dopaminergic (15). I-NAc, inxalenye ye-ventral striatum, ifumana i-afferents kwi-amygdala (16) kunye ne-prefrontal cortex (17), kunye ne-dopaminergic afferents ukusuka kwindawo ye-ventral tegmental (18). I-NAc ithathwa njengengundoqo ekuguquleleni inkuthazo kwisenzo (19) kwaye ingundoqo kwezinye iingcamango zangoku malunga ne-neurobiological underpinnings yokuthatha umngcipheko wokufikisa kunye nokufuna imvakalelo (5, 20, 21).
iziphumo
Umsebenzi weyunithi ye-Neural warekhodwa kwi-DS kunye ne-NAc (Umzobo weS1) ofikisayo (n = 16) kunye nabantu abadala (n = 12) iigundane njengoko zifunde ukudibanisa isenzo sesixhobo (i-poke) kunye nesiphumo somvuzo (i-pellet yokutya; Ikhiwane. 1A). Idatha yokuziphatha iboniswa ngokudibeneyo (Ikhiwane. 1 B-D), kuba akukho mahluko ngokwamanani abonwayo phakathi kwemimandla. Kwakungekho mahluko abalulekileyo anxulumene nobudala kulo lonke uqeqesho kwinani leemvavanyo ngeseshoni nganye [F(1, 1) = 1.74, P = 0.20]; ukubambezeleka ukusuka kumqondiso ukuya kwipoke yesixhobo [F(1, 1) = 0.875, P = 0.36]; okanye i-latency ukusuka kwisixhobo sokuxhoma ukuya ekungeneni kwindawo yokutya [F(1, 1) = 0.82, P = 0.36]. I-latency ukusuka kwi-cue ekuqaleni ukuya kwi-instrumental poke ibonakala yahlukile kwiiseshoni zokuqala, nangona oku kwakungabalulekanga ngokwezibalo kwaye kwakuqhutywa zizilwanyana ezithathu zangaphandle ezazingekafundi umbutho (Ikhiwane. 1C, Inset). Ukususela kwiseshoni yesi-4 ukuya phambili, onke amanyathelo afikelele kwinqanaba elizinzileyo kuwo omabini amaqela obudala. Ngexesha lezi seshoni umndilili wokubambezeleka kwabantu abadala kunye nabafikisayo ukusuka kwisixhobo sokuphendula ekungeneni kwindawo yokutya yaba (ithetha ± SEM) 2.47 ± 0.12 s kunye ne-2.54 ± 0.17 s, ngokulandelelanayo.
Iimpendulo ze-DS ze-neural ezihambelanayo malunga ne-instrumental poke kunye nokungena kwi-trough trough zabonwa njengoko iigundane zifunde i-action-outcome association kwaye zenza izilingo ezininzi kwiseshoni nganye (okt, iiseshoni ze-4-6; Umzobo weS2A). Uvavanyo olusondeleyo lwalo msebenzi ngexesha leeseshoni ze-4-6 lubonisa ukufana kumsebenzi wamaqela athile e-neuronal, kodwa ukungafani okukhulu kwabanye (Ikhiwane. 2). Malunga ne-10% yee-neuron ezirekhodiweyo ziye zasebenza kwi-cue-ukuqala kwesilingo, kunye neeseli ezimbalwa ziye zathintelwa.Ikhiwane. 2 A kwaye C, ekhohlo). Ukusasazwa kolutsha kunye nenqanaba lokudubula kwabantu abadala ZAmanqaku ayengahlukanga ngeli xesha (Z = 1.066, P = 0.29; Ikhiwane. 2B, ekhohlo). Kwakungekho mahluko unxulumene nobudala kubungakanani be-neurons esebenzayo, evaliweyo, kunye nengabalulekanga kwi-cue [χ]2(2, n = 570) = 2.35, P = 0.31; 1 Table]. Umyinge weeseli ezisebenzayo kunye nobukhulu bomsebenzi wonyukile kuwo omabini amaqela phambi kwempendulo yesixhobo, nangona oko kukhula kukhulu kwabakwishumi elivisayo (Z = -2.41, P = 0.02; Ikhiwane. 2B, Center). Umahluko onxulumene nobudala kubungakanani bohlobo lokuphendula ngexesha le-0.5 s ngaphambi kokuba i-instrumental poke ibaluleke [χ2(2, n = 570) = 10.01, P <0.01], isiphumo esiqhutywa sisixa esikhulu sabantu abadala abanqandekileyo (Z = 3.05, P <0.01; 1 Table). Ngokukhawuleza emva kwempendulo yesixhobo, iiseli ezazisebenza ngaphambili zavalwa, njengoko kwenza iiyunithi ezininzi ezingazange zisebenze ngaphambili (Ikhiwane. 2A, Center). Oku kukhokelele ekuphambukeni okuhlayo okwexeshana kwimisebenzi yabemi, eye yanda kwakhona kumazinga athile ngokweminyaka yobudala, kunye nokwahluka kwamanani okuqhubeka phakathi kolutsha kunye nomsebenzi wabantu abadala ngexesha le-0.5 emva kwempendulo yesixhobo (Z = 2.19, P = 0.03; Ikhiwane. 2B, Center). Ngeli xesha umlinganiselo weentlobo zeempendulo kwakhona zahluka phakathi kwezi zimbini [χ2(2, n = 570) = 10.57, P <0.01], ngenxa yomlinganiselo omkhulu weeyunithi zabantu abadala (Z = 2.87, P <0.01; Ikhiwane. 2C, Center kwaye 1 Table). Uninzi lwee-neuron ezifanayo ezandisa umsebenzi wazo phambi kokuba i-instrumental poke ithintelwe okwethutyana kwaye emva koko isebenze kwakhona ngaphambi kokungena kwindawo yokutyela (iirowu zobushushu ezibonisa ipateni ebomvu-blue-bomvu Ikhiwane. 2A, Center). Ixesha lale pateni lahlukile phakathi kwabafikisayo nakubantu abadala. Ubungakanani obunobungakanani bee-neurons zokufikisa zahlala zisebenza de kwavuzwa. Ezo "neurons zokulindela umvuzo" zazinqabile kubantu abadala (Ikhiwane. 2A, Kunene). Ukongeza kwiyantlukwano ekuhambeni kwexesha, ii-neurons zokufikisa eziye zasebenza kwi-0.5 s ngaphambi kokungena kwindawo yokutya nazo zanda kakhulu ngobungakanani obuphezulu (Z = -7.63, P <0.01; Ikhiwane. 2B, Kunene). Le pateni iyonke yomsebenzi ibizinzile kuzo zonke iiseshini 4-6 (Umboniso bhanyabhanya S1), nangona isampulu engacwangciswanga yeeyunithi ibonisa ukuguquguquka kweyunithi kwezinye iiyunithi (Umzobo weS3). Umlinganiselo weeyunithi ezivuliweyo nezithintelweyo zahlukile [χ2(2, n = 570) = 41.18, P <0.01], kunye nolutsha kunye nabantu abadala, ngokulandelelana, benomlinganiselo omkhulu kakhulu wokucutshungulwa (Z = -6.21, P <0.01) kunye neeyunithi ezithintelweyo (Z = 4.59, P <0.01; Ikhiwane. 2C, Kunene kwaye 1 Table). Kwi-0.5 s emva kokufikelela kwindawo yokutya, ulutsha luqhubekile nokubonisa umsebenzi onamandla (Z = -6.43, P < 0.01). Ubungakanani bezinto ezisebenzayo, ezithintelweyo, kunye nezingabalulekanga zahlala zahlukile njengoko zazinjalo ngaphambi kokungeniswa kwindawo yokutya [χ2(2, n = 570] = 31.18, P <0.01; Ikhiwane. 2C, Kunene kwaye 1 Table). Kwakhona, abafikisayo babenenxalenye enkulu yeeyunithi ezisebenzayo (Z = -4.89, P <0.01) kunye nenxalenye encinci yeeyunithi ezithintelweyo ngeli xesha (Z = 4.36, P <0.01).
Kwi-NAc, umndilili wokufikisa kunye nomsebenzi we-spiking wabantu abadala uhambe kwiimpendulo ezincinci okanye eziguquguqukayo ezinxulumene nomsebenzi ukuya kwiipateni ezingaguqukiyo (Umzobo weS2B). Ngeseshini yesi-4, omabini amaqela abe nokunyuka okufanayo kunye nokunciphisa umsebenzi we-phasic kwi-instrumental poke. Le pateni yachazwa ngakumbi ekhokelela kunye nokulandela umvuzo (ukungena kwisitya sokutya). Uvavanyo olusondeleyo lomsebenzi we-NAc phasic neural lubonisa ukufana okusondeleyo kwipatheni kunye nobungakanani bokusebenza kwe-neuronal kunye nokuthintela, kunye nolunye umahluko obonakalayo (Ikhiwane. 3). Ngokukodwa, ukuqala kokukhanya kwe-cue kukhokelele ekubeni kusebenze malunga ne-10% ye-neuron ye-NAc kubo bobabini abafikisayo kunye nabantu abadala, kunye ne-neuron ezimbalwa ezithintelwayo, kwaye akukho mahluko ubalulekileyo onxulumene nobudala kwinxalenye ye-neurons esebenzayo okanye ethintelweyo ngeli xesha [ χ2(2, n = 349) = 1.51, P = 0.47], kwaye akukho mahluko kwimisebenzi yabantu ngokubanzi (Z = 1.82, P = 0.07; Ikhiwane. 3, ekhohlo). Nje ukuba ii-neuron zisebenze kulingo, zazihlala zisebenza de isilwanyana singene kwindawo yokutya. Amandla exeshana ayenjalo kangangokuba umlinganiselo othile we-neurons uye wasebenza ngamandla ukujikeleza zombini i-poke yesixhobo kunye nokungena kumkhombe wokutya. Akukho mahluko unxulumene nobudala kumsebenzi wabemi (Z = -0.16, P = 0.87) okanye umlinganiselo wodidi lweyunithi [χ2(2, n = 349) = 0.22, P = 0.90] zifunyenwe kwi-0.5 s eyandulela i-instrumental poke. Emva komdlalo wesixhobo, abantu abadala babonisa umsebenzi ophakathi (Z = 4.09, P < 0.01) kunye nomahluko kuluhlu lweyunithi [χ2(2, n = 349) = 7.23, P = 0.03] ngenxa yomlinganiselo omkhulu we-neurons yabantu abadala (Z = 2.53, P = 0.01; Ikhiwane. 3C, Center kwaye 1 Table). Ngokufanayo, umndilili ophezulu wokusebenza kwabantu abadala wabonwa kwii-0.5 s ngaphambi kokungena kwindawo yokutya (Z = 2.67, P <0.01), kwaye kwakhona, umlinganiselo wodidi lweyunithi olwahlukileyo lwabonwa [χ2(2, n = 349) = 6.64, P = 0.04] ngenxa yobungakanani obukhulu beeyunithi zabantu abadala (Z = 2.32, P = 0.02; Ikhiwane. 3C, Kunene kwaye 1 Table). Ngeli xesha, umsebenzi wovavanyo-ngovavanyo we-neural usabonisa umlinganiselo othile wozinzo, nangona kunjalo ngaphantsi kwe-DS (Umboniso bhanyabhanya S2). Kwakungekho mahluko ubalulekileyo onxulumene nobudala kwimisebenzi yabemi kwi-0.5 s emva kokungena kwindawo yokutya (Z = -0.61, P = 0.54), nangona umahluko womyinge weyunithi ubukhona [χ2(2, n = 349) = 7.81, P = 0.02]. Oku kubonise umlinganiselo omkhulu kakhulu weyunithi ethintelweyo yokufikisa ngeli xesha (Z = -2.81, P <0.01; Ikhiwane. 3C, Kunene kwaye 1 Table). Ngaloo ndlela, nangona kukho ukungafani phakathi kwamaqela, ipateni ngokubanzi yeempendulo ze-neural (kunye nomsebenzi kwiiyunithi) yayifana kakhulu kwi-NAc kune-DS.
I-avareji yee-spectrogram ze-LFP eziqhelekileyo zazifana kulutsha kunye nabantu abadala kuzo zombini i-NAc kunye ne-DS (Ikhiwane. 4). Ngaphambi kokungena kwindawo yokutya, kwi-NAc, bobabini abakwishumi elivisayo kunye nabantu abadala babonise amandla anciphileyo kwiibhendi ze-β (13-30 Hz) kunye ne-γ (> 30 Hz), kunye nokunciphisa okubanzi kwe-γ-amandla kubantu abadala. Emva kokungena kwindawo yokutya, omabini amaqela abonise ukunyuka okwethutyana kwe-β-amandla okugxile kwi-20 Hz. Kwakukho utyekelo lwamandla amakhulu e-LFP yokufikisa kwi-frequencies ephantsi njenge-θ (3-7 Hz) kunye ne-α (8-12 Hz), kunye nokwahlukana okukhulu okunxulumene nobudala kufunyenwe ~500 ms emva kokungena kokutya (Ikhiwane. 4 A kwaye B). Iipateni ezifanayo zabonwa kwi-DS, kunye nokonyuka okunamandla kancinane kwabantu abadala ku-β-amandla ngoko nangoko emva kokungena kwindawo yokutya (Ikhiwane. 4 C kwaye D). Lilonke, iimephu zochasaniso lwamanani (Ikhiwane. 4 B kwaye D) bonisa ukufana komsebenzi onxulumene nomvuzo we-LFP wolutsha kunye nabantu abadala kuwo onke amaza amaninzi, ngaphandle kwezinto ezininzi eziphawulweyo.
ingxoxo
Sifumene i-activation eyomeleleyo enxulumene nomvuzo kumntwana ofikisayo kodwa ongenguye umntu omdala i-DS, isakhiwo esihambelana nokwenziwa kwemikhwa kunye nolawulo oluguqukayo lweepatheni zokuziphatha (11-13, 22). I-NAc iphendule ngokufanayo kumaqela omabini ubudala; nangona umahluko othile weyunithi yomsebenzi ubonwe kwi-NAc, lo mahluko wawuncinci kwaye udlula, kwaye ixesha lomsebenzi we-neural lalifana kakhulu phakathi kwamaqela kulo mmandla. Ezi ziphumo zibonisa i-heterogeneity yengingqi enxulumene nokusetyenzwa komvuzo ekuvuthweni kokusebenza kwezakhiwo ze-basal ganglia ngexesha lokufikisa kwaye, kunye ne-DS, icebisa indawo esele ingahoywanga ngaphambili yomahluko wokufikisa we-neural wokufikisa onokuthi unxibelelene ngokuthe ngqo nobuthathaka obunxulumene nobudala. Siphinde safumanisa ukuba nangona umahluko obalulekileyo onxulumene nobudala ubonwe kwinqanaba leyunithi, loo mahluko awuzange ubonakale ngokulula kumandla e-LFP oscillations, afana ngakumbi neempawu zengingqi ezinkulu ze-fMRI kunye ne-EEG (23).
Idatha ye-Phasic neural activity iphakamise ukuba indima echanekileyo ye-DS ngexesha lokulindela umvuzo, okanye impembelelo ye-stimuli evuzayo kumboniso wayo we-neural, yahlukile kulutsha olufikisayo kunye nabantu abadala. Omabini amaqela aneeyunithi eziye zasebenza ekuqaleni kolingo, zithintelwe ngokufutshane kwimpendulo yesixhobo, kwaye zaphinda zasebenza kwakhona. Phakathi kwezi, ngokuhambelana nezinye izifundo, iiyunithi zabantu abadala zavuselelwa kwangaphambili kwaye zabuyiselwa kwisiseko ngaphambi komvuzo (24, 25). Ukwenziwa kusebenze koogxa babo abafikisayo, ngokuchaseneyo, kwaqhubeka yonke indlela ukuya kwixesha lokufumana umvuzo. Ke, lulutsha kuphela olwaluneqela elikhulu lezinto ezinokuchazwa njenge-neuron zokulindela umvuzo kwi-DS. Nangona abanye baye bawubona ngaphambili umsebenzi wangaphambili kwi-DS (24-26), ingongoma ebalulekileyo apha kukuba abakwishumi elivisayo kunye nabantu abadala banebhalansi eyahlukileyo kunye nekhosi yexesha kwiipatheni zabo zomsebenzi onjalo. I-striatum icingelwa ukuba idlala indima ngqo kwimeko-intshukumo yemibutho (25) kwaye inokusebenza njengomdlali weqonga “kumdlali-umgxeki” wendlela yokuziphatha ethatha icala kwizenzo eziluncedo ngakumbi (27). I-striatum ifumana igalelo le-dopamine ukusuka kwi-substantia nigra kunye noqikelelo lwe-glutamate oluvela kwimimandla ye-cortical; ithumela uqikelelo lwe-GABA kwiglobus pallidus, eqhubela phambili iiprojekthi kwithalamus, ekugqibeleni ijike ibuyele kwicortex. Imiqondiso ehlukeneyo evela kwi-cortex yangaphambili ye-prefrontal okanye imimandla ye-basal ganglia inokuthatha i-akhawunti yeepateni zeminyaka ethile ebonwa ngoku kwi-DS. Ewe, ngaphambili siye sabona ukunciphisa inhibition kunye nokwanda kokusebenza kwinxalenye ye-orbitofrontal cortex (OFC) ngexesha lalo msebenzi (28), eziprojekthi ngqo kulo mmandla we-DS (29).
Ngokuhambelana neengxelo zangaphambili zokunyuka kwe-LFP θ- kunye ne-β-oscillations kwi-DS ngexesha lokuziphatha ngokuzithandela (30, 31), abafikisayo kunye nabantu abadala babonise ezi zinto ngaphambi nasemva kokungena emkhombeni wokutya. Nangona kukho umahluko omkhulu weyunithi enye kwi-DS, i-oscillations ye-LFP yayifana kakhulu phakathi kwamaqela amabini eminyaka kwi-DS kunye ne-NAc. Oku kufunyanisiweyo kubalulekile kuba izifundo zabantu abafikisayo zijolise kumanyathelo amakhulu okusebenza afana ne-fMRI kunye ne-EEG. Sibonisa ukuba iyantlukwano yeyunithi enxulumene nobudala inokufumaneka naxa i-oscillations yengingqi enkulu, ehambelana ngcono neempawu ze-fMRI, ziyafana.23). Nangona imisebenzi ye-basal ganglia LFP oscillations ingaziwa, imodareyithwa yimeko yokuziphatha (30, 31), into efanayo kumaqela amabini eminyaka ubudala.
Kwi-NAc, ngaphandle kwezinye iiyantlukwano ezidlulayo, umlinganiso wabasebenzi abaqeshwayo kunye neeyunithi ezithintelweyo, kunye nexesha lexesha leempendulo zabo, bezifana ngokubanzi, njengoko kubonisiwe kumndilili oqhelekileyo womsebenzi wabantu. Ukusetyenziswa kwe-NAc kuchaphazela inkuthazo, umsebenzi osisiseko wokuziphatha, kunye nokufunda kunye nokwenziwa kokuziphatha kwezixhobo (32-35). Kuphononongo lwangoku, umahluko wemisebenzi ye-neural yokufikisa kwi-NAc yayithozamile kwaye ithatha ixeshana xa ithelekiswa nezo zikwi-DS. Izifundo ze-fMRI ebantwini azihambelani xa kuthelekiswa nomsebenzi onxulumene nomvuzo we-NAc kulutsha olukwishumi elivisayo ngokuchasene nabantu abadala. Ezinye izifundo zibonise imiqondiso eyomeleleyo ye-NAc yokufikisa ukuvuza (36, 37) kwaye abanye bafumene ababuthathaka (38) okanye iipateni ezinzima ezixhomekeke kumxholo (39). Olu phononongo, olurekhoda i-subcortical single-unit kunye nomsebenzi we-LFP kulutsha oluziphethe kakuhle, lunika ukukhanya kulo mbandela: sibonisa ukuba umahluko onjalo onxulumene nobudala unokuxhomekeka kuhlobo lwesiginali elinganisiweyo. Iziphumo zethu zikwahambelana nobungqina bangaphambili bokuba ukuvuthwa okusebenzayo kufikeleleke kwi-NAc ngaphambili kuneminye imimandla efana ne-OFC (37, 28). Nangona kunjalo, ekufumaniseni ukuba umsebenzi weyunithi ye-DS yokufikisa wahlukile kulowo wabantu abadala, sigqiba kwelokuba lo ayisiyonto nje yokwahlukana kwecortical vs. subcortical njengoko bekucetyiwe.40).
Kubalulekile ukugxininisa ukuba umahluko womsebenzi we-neural kuphononongo lwangoku uqatshelwe ngaphandle kokusilela komehluko wokuziphatha olinganisiweyo. Ngenxa yendima ye-DS ekuqhutyweni kweepateni zokuziphatha, ukungafani kwe-neural kunokuba ngenxa yenxalenye yokungafani kokuziphatha okungenakulinganiswa. Nangona lo mahluko usoloko unokwenzeka, kolu phononongo lwangoku lubonakala lungenakwenzeka ngenxa yezizathu ezimbalwa. Ukuthelekiswa kwe-Neural kwenziwa kuphela xa iigundane zinobuchule obuphezulu kunye nomsebenzi kwaye zabonwa ukuba zijolise kakhulu kumsebenzi. Elona xesha lomahluko mkhulu we-neural yayilixesha eliphakathi kwempendulo yesixhobo kunye nokungena kwindawo yokutya, ngelixa umyinge wokubambezeleka kolu kuziphatha wawufana nqwa kumaqela amabini obudala. Ngapha koko, iyantlukwano ye-neural ibisoloko ibonwa kwiindawo ezithile (umzekelo, ngexesha lolindelo lomvuzo) kodwa hayi abanye (umzekelo, impendulo kwisilingo sokuqala), kwaye nangona ixesha le-neuronal activation lihlala lihluka kakhulu, ixesha le-neuronal inhibition. yayifana ngokubanzi kuyo yomibini imimandla yobuchopho yeqela ngalinye lobudala. Ngokudibeneyo, ezi ziphumo ziyahambelana nokutolikwa kokwahluka okusisiseko okunxulumene nobudala be-neural processing, ngakumbi kwi-DS, nangexesha lokuziphatha / iimeko ezifanayo, ezithetha ngomahluko kuyilo lwe-neural, ukusebenza kakuhle, kunye / okanye impembelelo ye-physiological ye-salient. iziganeko.
Ukuqukumbela, sifumanise ukuba iziganeko ezinxulumene nomvuzo zingena ngamandla kwi-DS yolutsha kodwa hayi abantu abadala, enokubonisa indawo entsha ngaphakathi kuthungelwano olunoxanduva lokuziphatha okunxulumene nobudala kunye nokuba sesichengeni kwengqondo. Esi sakhiwo se-basal ganglia sidlala indima ephambili ekufundeni okuqhelekileyo kunye nenkumbulo, ukubunjwa komkhwa, kunye neminye imiba yokuziphatha ekhuthazwayo, kwaye ukungasebenzi kwayo kuhambelana neengxaki zengqondo (41-43). Ke ngoko, ukufunda ngakumbi malunga nendlela umsebenzi walo mmandla oguquka ngayo ngophuhliso, kunye nokunxibelelana kwayo neminye imimandla ephambili yobuchopho, kuya kuba yimfuneko ekuqondeni kwethu iindlela zobuthathaka bokufikisa kunye noyilo lwexesha elizayo longenelelo lwezonyango. Ukuntsokotha kokuziphatha kolutsha kunye nokuba sesichengeni ngokwasengqondweni kunokwenzeka ukuba kunezinto ezininzi, kubandakanya imimandla emininzi yobuchopho. Ke, i-DS yenye yemimandla emininzi enxibelelanayo ethi kunye (kwaye ingengawodwa) ibaluleke kakhulu kubuthathaka bokuziphatha kunye nengqondo yokufikisa. Siyathemba ukuba ngobuchule obufana nokurekhoda kwe-electrophysiological yokufikisa kunye nendlela yokuziphatha ebambekayo yokufunda umahluko onxulumene nobudala be-neural processing kwiimeko zokuziphatha, sinokuqala ukuxabisa i-substrates yokuba sesichengeni sokufikisa kwinqanaba lenethiwekhi.
Impahla nenkqubo
Izifundo kunye noTyando.
Iinkqubo zezilwanyana zivunyiwe yiYunivesithi yasePittsburgh yezilwanyana kunye neKomiti yoSetyenziso. Umntu omdala oyindoda (usuku lokubeleka 70–90, n = 12) kunye nedama elikhulelweyo (usuku lwe-embryonic 16; n = 4) Iigundane ze-Sprague-Dawley (i-Harlan) zigcinwe kwi-vivaria elawulwa yimozulu kunye ne-12-h ukukhanya / umjikelezo omnyama (izibane kwi-7: 00 PM), kunye nokufikelela kwe-ad libitum kwi-chow namanzi. Iilitha zaye zakhutshelwa ukuba zingabi ngaphezu kwesithandathu amantshontsho angamadoda, athi ke alunyulwe ngosuku lwasemva kokubeleka kwama-21.n = 16). Utyando lwabantu abadala lwenziwa emva ubuncinane beveki enye yokuhlala kwizindlu. Utyando lokufikisa lwenziwa ngosuku lokubeleka kwe-1-28. Uluhlu olusibhozo lwe-microelectrode arrays lwafakwa kwi-NAc okanye kwi-DS (Izinto ze-SI kunye neendlela). Urekhodisho lwenziwa njengoko bekuchaziwe ngaphambili (28) ngelixa iimpuku zenza umsebenzi wokuziphatha. Iiyunithi enye zaye zabekwa zodwa kusetyenziswa i-Offline Sorter (Plexon) ngokudityaniswa kobuchule bokuhlela ngesandla kunye ne-semiautomatic (44).
Ukuziphatha.
Iinkqubo zovavanyo lokuziphatha zenziwa njengoko kuchaziwe ngaphambili (28, 45). Iimpuku zafunda ukwenza i-instrumental poke yemivuzo yepellet yokutya (Ikhiwane. 1A kwaye Izinto ze-SI kunye neendlela). Kwiseshoni nganye, inani elipheleleyo leemvavanyo, umyinge we-latency ukusuka kwisilingo-ukuqala kwi-cue kwi-instrumental response, kunye ne-latency evela kwi-instrumental response to retrieval retrieval yavavanywa. Ubudala × iseshoni yokuphindaphinda-imilinganiselo ye-ANOVAs yenziwe ngokusebenzisa isofthiwe ye-SPSS kuwo onke la manyathelo (α = 0.05), kunye nezilungiso eziphantsi kwe-df apho ukucinga kwe-sphericity kwaphulwa.
Uhlalutyo lwe-Electrophysiology.
Idatha ye-Electrophysiological yahlalutywa kusetyenziswa izikripthi zeMatlab (MathWorks) ezibhalwe ngokwesiko kunye nemisebenzi esuka kwibhokisi yesixhobo yeChrronux (http://chronux.org/). Uhlalutyo lweyunithi enye lwalusekwe kwi-histograms yesantya sexesha lokudubula kwiifestile malunga nemisitho yomsebenzi. Umsebenzi weyunithi enye wawu Z-inqaku eliqhelekileyo elisekelwe kumlinganiselo kunye nemilinganiselo yokudubula ye-SD yeyunithi nganye ngexesha lesiseko (i-window ye-2 iqala i-3 s ngaphambi kokuqala kwe-cue). Umndilili womsebenzi weyunithi yabemi wacwangciswa malunga nemisitho yomsebenzi. Ukuthelekiswa kwamanani olutsha kunye nomsebenzi weyunithi yabantu abadala kwenziwa kwixesha eliphambili leefestile zomdla (iifestile ze-0.5-s emva kwe-cue, ngaphambi nangemva kwe-instrumental poke, nangaphambi nangemva kokungena kwindawo yokutya) kusetyenziswa iimvavanyo ze-Wilcoxon ze-rank-sum. iboniswe njenge Z-amaxabiso), i-Bonferroni ilungiswe ukuthelekisa ezininzi. I-hypothesis engekhoyo yakhatywa kolu hlalutyo xa P 0.01. Iimuvi S1 kwaye S2 mele indawo eqikelelweyo ye-scatterplot egudileyo (LOESS) i-avareji yezinga lokudubula eliqhelekileyo kwizilingo ezintlanu ezihamba ngamanyathelo ovavanyo olunye ngokusebenzisa iifreyimu zevidiyo ngexesha leseshini ye-4-6. Ixesha levidiyo limele inguquko yomsebenzi ngovavanyo lweseshini nganye. IiYunithi nazo zahlelwa njengezenziwe zasebenza okanye zavalwa kwiifestile zexesha elithile ukuba zinemigqomo emithathu elandelelanayo ye-50-ms ene. Z ≥ 2 okanye Z ≤ −2, ngokulandelelanayo. Ezi nqobo zokugweba ziye zaqinisekiswa njengezivelisa amazinga asezantsi okuhlelwa kobuxoki ngohlalutyo lwe-nonparametric bootstrap njengoko kuchaziwe ngaphambili (39) (Izinto ze-SI kunye neendlela). Emva kokuba iiyunithi zihlelwe, χ2 uhlalutyo lwenziwa kwiifestile eziphambili zomdla kuzo zonke iiyunithi ezisebenzayo, ezithintelweyo, kunye nezingabalulekanga. Okubalulekileyo kuphela χ2 iimvavanyo zilandelwe yi post hoc Z-ivavanya imilinganiselo emibini ukufumanisa umahluko osisiseko wodidi olubalulekileyo. I-hypothesis engekhoyo yakhatywa xa P <0.05, eboniswe kwi 1 Table ngodidi olungqindilili. Ukubona ikhondo lexesha lokufunwa kweyunithi (okt, njengoko ivuliwe okanye ivaliwe), uhlalutyo lwecandelo lwenziwa kwiifestile ze-500-ms ezihambayo (ngamanyathelo angama-250-ms) kwiifestile ezinkulu ixesha elivaliweyo kwiziganeko zomsebenzi.
Emva kokususa izilingo apho umkhondo wamandla ombane e-LFP ekrwada equlathe izinto zakudala ezichetywayo okanye izinto ezingaphandle (± 3 SD ukusuka kumbane ophakathi), i-spectra yovavanyo oluyi-avareji yovavanyo ibalwe kwisifundo ngasinye kusetyenziswa uguqulo olukhawulezayo lweFourier.Izinto ze-SI kunye neendlela). Umboniso wamandla ubuphakathi kwiqela ngalinye lobudala. T-imephu yokuthelekisa amanqaku ethelekisa amandla e-LFP aqhelekileyo olutsha kunye neespectrogram zabantu abadala ngexesha ngalinye × umgqomo wamatyeli acwangcisiweyo ukuqaqambisa ukufana okunxulumene nobudala kunye nomahluko.
Imibulelo
Inkxaso yalo msebenzi yanikezelwa yiZiko leSizwe leMpilo yengqondo, i-Pittsburgh Life Sciences Greenhouse, kunye ne-Andrew Mellon Foundation Predoctoral Fellowship (kwi-DAS).
Imihlathi
Ababhali bavakalisa ukuba akukho mpikiswano.
Eli nqaku lingeniso ngqo lwe-PNAS.
Eli nqaku liqulethe iinkcukacha ezixhasayo kwi-intanethi www.pnas.org/lookup/suppl/doi:10.1073/pnas.1114137109/-/DCSupplemental.
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