Prefrontal cortical regulation ea boits'oaro ba potoloho ea potoloho le boitšoaro bo amanang le moputso (2016)

Mahlale 1 Pherekhong 2016: Moq. 351 che. 6268

DOI: 10.1126 / science.aac9698

  1. Emily A. Ferenczi1,2,*,
  2. Kelly A. Zalocusky1,2,*,
  3. Conor Lethathamo3,*,
  4. Logan Grosenick1,2,
  5. Melissa R. Warden4,
  6. Debha Amatya1,
  7. Kiefer Katovich5,
  8. Hershel Mehta5,
  9. Brian Patenaude6,
  10. Charu Ramakrishnan1,
  11. Paul Kalanithi7,
  12. Amit Etkin6,
  13. Brian Knutson5,
  14. Gary H. Glover8,
  15. Karl Deisseroth1,4,9,

inahaneloang

Khothatso ea moputso e khanna boits'oaro bo feto-fetohang, athe ho senyeha hoa pono ea moputso le boiphihlelo (anhedonia) ho ka kenya letsoho mafu a mafu a kelello, ho kenyelletsa khatello ea maikutlo le lefu la kelello. Re ne re batla ho leka hypothesis ea hore medial prefrontal cortex (mPFC) e laola tšebelisano har'a libaka tse ikhethileng tse arabelang likarabo tsa hedonic. Ka ho sebelisa optogenetic tšebetso e nang le matla a tšebetso ea matla a khoheli ho sebetsana le litloaelo tsa lehae empa re bona liketsahalo tsa lefats'e lefatšeng ka bophara litšoantšong, re fumane hore ts'oaetso ea dopamine neuron e letsa ts'ebetso ea striatal, athe thabo ea lehae ea MPFC e fokotsa karabelo ena e sitisang le ts'ebetso ea boits'oaro ea dopaminergic. Ts'ebetso ena e fetelletseng ea mPFC e boetse e hatella boits'oaro bo botle bo susumetsoang ke moputso ebile e etsa hore ho be le litšebelisano tse ncha tse sebetsang bokong, tse boletseng esale pele hore na ho tla ba le bothata bofe bathong. Liphumano tsena li hlalosa mochine oo mPFC e fetotsang mokhoa oa ho batla meputso ka ho laola tšebelisano e matla lipakeng tsa libaka tse ikhethileng tse hole.

Mokhoa oa ho latela mokhoa oa ho batla moputso

Ke likarolo life tsa boko tse nkang karolo ka botlalo boitsholong bo amanang le moputso? Ferenczi et al a. tse kopantsoeng tse ikhethileng, mofuta oa sele e khethehileng, manong a li-optogenetic le monahano oa boko, tlhahlobo ea boits'oaro, le ho vivo electrophysiology (bona Perspective ke Robbins). Ho hlohlelletsa li-neurop tsa dopamine neuron ho eketsang tšebetso karolong ea boko e bitsoang striatum 'me e ne e hokahanngoa le ho batla meputso ho liphoofolo ka bomong. Leha ho le joalo, thabo e phahameng ea sebaka se bitsoang medial preambilial cortex e ile ea fokotsa likarabo ka bobeli tsa ts'usumetso ea ts'usumetso ea li-dopamine neurons le boits'oaro ba boits'oaro ba ho batla ho tsosa li-neurone tsa dopamine. Kamora nako, ho fetola ho nyakalla ha medial prefrontal cortex pyramidal neurons ho tsamaisitse liphetoho ho li-synchrony tsa neural, hammoho le boitšoaro bo lumellanang ba anhedonic. Maikutlo ana a tšoana le monahano le liketsahalo tsa bongaka tse bonoang khaellong ea motho, bokhoba ba ho lemalla le lefu la kelello.

SELELEKELA

Sepheo sa ho batla le ho fumana moputso se bolokiloe ho mefuta eohle, 'me ho liphoofolo tse anyesang ho kenyelletsa tšebelisano lipakeng tsa lits'ebetso tse tlase tsa dopaminergic le litho tsa maoto tse kang striatum. Ho sitisoa ha ts'ebetso ena, ho bonoang maemong a mangata a kelello, ke letšoao la bokuli (anhedonia). Mekhoa ea neural e ka tlase ho anhedonia ha e tsejoe empa e ka hlaha ka lebaka la tšebelisano e sa tloaelehang lipakeng tsa li-circuits tsa moputso oa cortical le subcortical. Re ne re batla ho leka hypothesis e phahamisang medial prefrontal cortex (mPFC) thabo (tšobotsi ea bongaka e amanang le anhedonia) e nang le taolo e hatelletseng ea tšebelisano pakeng tsa libaka tse peli tse hole haholo: dopaminergic midbrain le striatum.

RETS'ELISITSOE

Lithuto tsa ho nahana ka bophelo bo botle ba bongaka li hlokometse ts'ebetso e phahameng ho mPFC ho bakuli ba batho ba nang le khatello ea maikutlo, 'me kalafo e tsamaisana le ho tloaeleha ha ts'ebetso ena e fetisisang le ntlafatso ea matšoao a anhedoniki. Ho feta moo, lithuto tsa batho li thathamisitse libaka tsa boko tse arabelang ho putsa tebello le boiphihlelo, mme karabelo ena e ka hatelloa ho lefu la mafu a kelello. Leha ho le joalo, mohloli oa lets'oao lena la moputso le mekhoa e tsamaisang phetoho ea eona ha e so hlahisoe hantle. Re kopantsitse mefuta e fapaneng ea lisebelisoa tsa optogenetic tse sa foleng le tse matla le tšebetso e sebetsang ea matla a matla a matla a fono (fMRI) ho fana ka borokho lipakeng tsa causal, ho hlaka hoa selikalikoe mabapi le lits'oants'o tsa methapo le lipono tsa bongoana tse bonts'ang ts'ebetso ea batho, ka sepheo sa ho laola le ho hlasela lefats'e ka bophara. ho bona liketsahalo tsa neural ho utloisisa taolo ea boitšoaro bo batlang moputso.

LIPOTSO

Re bonts'a hore tšusumetso ea li-neurb tsa dopamine neurons e khanna tšebetso ea bobeli ea boemo ba moea ba oksijene ea fMRI-e its'epahalletseng (BOLD) le boitšoaro bo batlang meputso, 'me re bonts'a hore tsena li amana le batho ka bomong. Ho kenyelletsa moo re fumana hore ho khutsisa ha dopamine neurons ho hatella ts'ebetso ho striatum, le libakeng tse ling tsa boko (joalo ka hypothalamus), le boitšoaro ba ho qoba ho otla. Ha re se re thehile taolo ena ea boipheliso ea boits'oaro ba ho batla moputso, re ile ra leka ho bona ho potoloha ha potoloho ena ka ho phahamisa thabo ea mPFC. Re hlokometse khatello ea likarabo tsa litla-morao ho dopamine, hammoho le ts'ebetso ea boits'oaro ea ho batla ts'usumetso ea dopamine neuron le tse ling tse khothatsang tsa tlhaho. Kamora nako, re bonts'a hore mPFC e phahameng haholo e thabisang e tsamaellanya corticolimbic BOLD le ts'ebetso ea elektrone, eo ka eona e ka bolelang boitšoaro ba anhedonic ho liphoofolo ka bomong.

QETELLO

Seo re se fumaneng ho tsoa ho liteko tse kenyelletsang taolo e ikhethang ea sele, ka nako e ts'oanang le ts'ebetso ea lefats'e e sa hlokeng botsitso ea ts'ebetso ea neural, se senola hore mPFC e fana ka taolo e tlase holim'a ts'ebelisano ea dbaminergic le ts'ebelisano le hore, ha e phahame, ts'ebetso ho MPFC e ka hatella moputso oa tlhaho boits'oaro bo khahlisang. Ntle le moo, re hlokomela hore matla a "cortical-subcortical neural dynamics a sebetsa" concert ho laola ts'ebetso ea moputso. Liphetho tsena kaofela li na le moelelo kutloisisong ea rona ea 'mele le boits'oaro bo amanang le moputso, hammoho le pathogenesis ea anhedonia.

Optogenetic fMRI e ne e sebelisetsoa ho laola le ho bona lefatše ka bophara tšebetso ea neural e amanang le moputso. Liroto tse tloaeloang li ile tsa hlahlojoa maemong a holimo (lifoto tse kaholimo). Re tiisa hore ts'ebetso ea striatal BOLD e eketsoa ke ts'usumetso ea optogenetic ea dopamine neurons mme e fokotseha ka optogenetic neural silencing. Re bonts'a hore mPFC e phahameng e tsepamisang maikutlo e hatella mokhoa oa ho batla moputso ka ho fana ka taolo e holimolimo holim'a ts'ebetso e tsitsitseng ea dopamine mme e khanna khokahano lipakeng tsa potoloho e khethehileng ea corticolimbic.