Lipotoloho tsa bokooa tsa bokhoba ba lithethefatsi li khethiloe: orbitofrontal cortex-dorsal striatum (2018)

LITABA LE BONOLO

19 December 2018

Likarolo tsa bokhoba ba lithethefatsi tse qobelloang li khethollotsoe

Phuputso e mabapi le litoeba e supa tloaelo ea boko e khothalletsang boitšoaro bo khothalletsoang bo amanang le bokhoba ba lithethefatsi, mme e ka hlalosang lebaka leo basebelisi ba lithethefatsi ba bang ba itšoarang ka matla ha ba bang ba sa e etse.

Lithethefatsi tsa tlhekefetso li na le litlamorao tse thata tsa pharmacological tse bakang liphetoho tse ngata tšebetsong ea boko. E 'ngoe ea litlamorao tsena, ts'ebetso e tobileng kapa e sa tobang ea li-neuron tse lokollang neurotransmitter dopamine, e tloaelehile ho lithethefatsi tsohle tsa tlhekefetso mme ke khale ho nahanoang hore e kenya letsoho kholisong ea bokhoba ba tahi. Ho ngola Nature, Pascoli et al a.1 tlaleha ka mekhoa ea "neurobiological" e hlahisoang ke ts'ebetso e pheta-phetoang ea li-dopamine neurons tse ka hlalosang hore na ke hobaneng basebelisi ba lithethefatsi ba bang ba batla moputso leha ba tobane le litlamorao tse mpe - mofuta oa boits'oaro bo hatelletsang boo e leng tšobotsi e hlalosang bokhoba ba batho2.

Bangoli ba nkile mokhoa oa optogenetics ho etsisa ts'ebetso ea ts'ebetso ea dopamine ea boko ka lithethefatsi tsa tlhekefetso: ba sebelisitse leseli la laser le fanoang ka fiber ea optical ho kenya ts'ebetsong li-dopamine neurons sebakeng sa ventral tegmental sebakeng (VTA) ea methapo ea kelello ea litoeba tsa lefutso. Litoeba li ka susumetsa methapo ena ka ho toba ka ho tobetsa lever, 'me ea etsa ketso ena ka mokhoa o hlakileng nakong ea liteko tsa metsotso ea 40 ka letsatsi bakeng sa libeke tsa 2.

Matsatsing a latelang, litoeba li ile tsa ts'oaroa ke motlakase ka motsotsoana ho kotara ea makhetlo a mararo ho isa linakong tse matla tsa motlakase. Boitšoaro ba bona tlasa maemo ana bo senotse ho fetoha ho makatsang: 40% ea litoeba (ba lahliloeng kherehloa) ba fokolitse makhetlo a mangata a khatello ha ba fuoa lits'oants'o tsa maoto (sa feiga. 1a), athe 60% (bahlorisi) ba neng ba ikemiselitse ho amohela bohloko kotlo bakeng sa monyetla oa ho itlhasimolla tsa bona tsa dopamine neurons (sa feiga. 1b). Joalokaha bangoli ba bang ba bona ba kile ba bontša3, litoeba tse mamellang li fana ka mohlala oa tšebeliso e mpe ea lithethefatsi leha e ka ba le litlamorao tse mpe, hape e tsamaisana le ts'ebeliso ea batho ba sebelisang lithethefatsi eo tšebeliso ea lithethefatsi e bang boima.

Setšoantšo sa 1 | Ts'ebetso e qobelloang ea li-dopamine neurons bokong. Phuputsong ea Pascoli et al a.1, litoeba li hatelletse lever ho kenya tšebetsong li-neurop tsa dopamine ka ho tsamaisa leseli la laser le tsamaisoang ke fiber ea mahlo. Li-neuron tsena, tse sebetsang ho tloha sebakeng sa "ventral tegmental" (VTA) ho ea ho ventral striatum bokong, li amahanngoa le moputso. a, Litoeba tse ling tse bitsoang ho lahloa kherehloa, li fokotsa boits'oaro ba khatello ha bo kopantsoe le ho ts'oaroa ke motlakase o bohloko maotong a bona. Matla a khokahano pakeng tsa li-neurons tsa orbitof Pambal cortex (OFC) e neng e kenella ho dorsal striatum e ne e le tlase ho litoeba tsena. b, Litoeba tse ling, tse bitsoang bahlorisi, li ntse li tsoela pele ho tobetsa ea lever leha e le kotlo - e leng lets'oao la boitšoaro bo hatellang. Khokahano ea neural lipakeng tsa OFC le dorsal striatum e ne e le matla ho litoeba tsena ho feta ho li-reneke. Ha bangoli ba fokolisa likhokahano tsena ho litoeba tsa mamello, boits'oaro bo matla ba liphoofolo bo ile ba fokotseha (ha bo bontšoe).

Ka mor'a moo bangoli ba ile ba leka ho fumana hore na ho ne ho fapane joang pakeng tsa batho ba bang le ba lahlapetsang. Ba lekantse tšebetso ea li-neurons tse hokahanyang libaka tse fapaneng tsa boko ka nako ea nnete ho bona hore na ke marang-rang afe a neng a sebetsa ha litoeba li hatella lever. Puisano pakeng tsa orbitof Pambal cortex (OFC), sebaka se kenyelletsoeng ho etsa liqeto, le dorsal striatum, e etsang ketso ea boithaopo, e ile ea eketseha pele ho tobetsa ea lever ho litoeba tse neng li ikemiselitse ho fumana litšitiso hammoho le ho ithorisa. Thibelo ea optogenetic ea tsela ena e neural e fetotse litoeba tse ntseng li phehella ho tlohela litoeba. Ho fumana hona ho bonts'a hore ts'ebetso e eketsehang ea li-neuron tse tsoang ho OFC ho ea ho dorsal striatum e ne e hlokahala bakeng sa mofuta ona oa ts'ebetso e qobellang ea dopamine neurons.

Leha ho le joalo, phetoho ena ea boits'oaro e ne e le ea nakoana feela: ha ts'ebetso ea optogenetic e emisoa, boitšoaro bo qobelloang bo ile ba qala hape ho litoeba tse mamellang. Bangoli ba ile ba beha lebaka la hore liphetoho tsa nako e telele li-synapses - li-pakeng tsa li-neuron - tse hokahanyang OFC le dorsal striatum neurons li ka hlaha ka lebaka la matsatsi a mangata a ho ikhatholla ha dopamine neurons. Haeba liphetoho tsena li etsahetse feela ho litoeba tse phehellang, hona ho ka hlalosa boitšoaro ba bona bo phehellang.

Haeba khopolo-taba ena e le 'nete, matla a khokahano ea synaptic pakeng tsa OFC le dorsal striatum neurons e lokela ho ba a maholo ho bakuli ho feta ho ba lahlang, ho thusa ts'ebetso e ntle ea li-neurons tsa dorsal striatum ka li-neuron tsa OFC. Ehlile Pascoli et al a. o ile a tsoela pele ho bonts'a hore matla a li-synapses pakeng tsa li-neuron tsa OFC le li-neurons tsa dorsal striatum li ne li eketsehile ho litoeba tsa mamello (Fig. 1). Barekisi, hammoho le litoeba tse neng li sa ka tsa pepesetsoa tlhahlobo le litoeba tse fumaneng litšoso empa li sa lumelloe ho sebelisa lever, kaofela li bonts'itse matla a fokolang a synaptic pakeng tsa OFC le dorsal striatum neurons.

Ho makatsang ke hore bangoli ba fumane hore boitšoaro bo qobelloang bo ka hatelloa kapa ba ts'oaroa ka ho fokotseha kapa ka ho eketsa matla a khokahano ena ea neural. Ho fokola ha khokahano ea synaptic pakeng tsa OFC le dorsal striatum ho litoeba tse ntseng li tsoela pele ho fokotsitse boikemisetso ba bona ba ho itlhasimolla ha ba tobane le ho ts'oaroa ha leoto. Ka lehlakoreng le leng, bahanyetsi ba ka fetoloa hore e be bakuli ka ho eketsa matla a likhokahano tsena tsa synaptic. Ho fapana le phetoho ea nakoana e ileng ea bonoa kamora hore optogenetic inhibition ea OFC neurons e qalelle ho dorsal striatum, liphetoho tsena ka matla a synaptic li ile tsa susumetsa phetoho ea boits'oaro e phehellang matsatsi a tšeletseng.

Makhulo et al a. ba fumane neuroadaptation e lumellang litoeba hore li fetele mohopolo o bohloko oa ho tsoela pele ho kenya tšebetsong li-neuron tsa bona tsa dopamine. Ts'ebeliso e mpe ea lithethefatsi tsa tlhekefetso ho batho e lebisa ho ts'ebetsong e tšoanang ea potoloho e tšoanang ea dopamine, ka hona, neuroadaptation e ts'oanang e ka etsa hore ba tsoelepele ho sebelisa lithethefatsi leha ho na le litlamorao tse mpe. Ho lekola tlhahiso ena, re lokela ho khetha hore na liphetoho tse matla pakeng tsa khokahano lipakeng tsa OFC le dorsal striatum neurons methapo ea boits'ebetso ea litoeba li hatella lever ho amohela koae, amphetamines kapa opioids ha e ka tšosoa ke leoto.

Na ts'usumetso ea optogenetic ea dopamine neurons e etsisa hantle ts'ebetso ea li-neurop tsa dopamine ke lithethefatsi tsa tlhekefetso? Ho na le liphapang tse totobetseng lipakeng tsa ho tima le ho tima ka potlako nakong ea ts'usumetso ea optogenetic le ho qala butle butle le nako e telele ea ketso ea lithethefatsi. Leha ho le joalo, bangoli ba kile ba bonts'a4 hore tšebeliso ea "cocaine" le ts'ebetso ea optogenetic e etsa hore phetoho e batlang e ts'oana le ena ho li-dopamine neurons le litheko tsa bona tsa phallo e potlakileng, e fane ka tumellano e matla bakeng sa mokhoa oa teko o sebelisitsoeng thutong ea hajoale.

Hobaneng ha ho ithorisa ha li-neurop tsa dopamine ho lebisa ho boits'oaro bo qobelloang ho ts'ebeliso e tlase ea batho ka bomong? Ho phehella le ho lahla litoeba li ikhutsitse hoo e batlang e le ka nako e ts'oanang le ka palo e ts'oanang ea liketsahalo pele likotlo tsa maoto a tšohanyetso li qalile, empa kelello ea lihlopha tsena tse peli e bonahala e fetohile ka litsela tse fapaneng. Li-neurons tsa VTA dopamine tse hlohlellelitsoeng ke litoeba ha li hokahane ka kotloloho le OFC kapa dorsal striatum, kahoo khokahano lipakeng tsa libaka tsena e tlameha ho kenyelletsa likhokahano tse ngata tsa synaptic. Tsela e nang le multisynaptic eo ka eona ts'ebetso ea li-neuropa tsa VTA dopamine e ka bakang liphetoho dorsal striatum e kile ea hlalosoa pejana.5, 'me ho khothalelitsoe ho etsa liphetoho tse tlisoang ke ho sebelisa lithethefatsi ntle le ho tlama6,7. Liphapang tse bileng teng pele ho potoloho ena ea multisynaptic li ka 'na tsa hlalosa hore na ke hobaneng boitšoaro bo tlamang, le liphetoho tse amanang le khokahano ea synaptic, li hlaha ho litoeba tse ling feela.

Liphetoho tsa Synaptic li ka nka matsatsi, lilemo kapa esita le bophelo bohle. Mohlomong liphetoho tse fumanoeng ke Pascoli et al a. theha motheo oa phetoho e sa feleng ea boitsoaro eo e leng lets'oao la bokhoba ba lithethefatsi? Ho araba potso ena ho tla hloka bopaki ba liteko ba ho itaola lithethefatsi le ha ho bile le litlamorao tse mpe ka ho matlafatsoa ha likhokahano lipakeng tsa OFC le dorsal striatum, le hore ke ts'ebetso ea lits'ebetso tsa dopamine e tsamaisang letoto la liketsahalo tsa neural tse qetellang ts'ebeliso e qobelloang ea lithethefatsi.

Nature 564E ETSOA KE: 349-350 (2018)

Doi: 10.1038 / d41586-018-07716-z