Ts'ebetso ea Optogenetic ea li-prefrontal cortex circuitry (2014)

Front Syst Neurosci. 2014; 8: 230.

E hatisitsoe Inthaneteng 2014 Dec 9. doi:  10.3389 / fnsys.2014.00230

PMCID: PMC4260491

Danai Riga, Mariana R. Matos, Annet Glas, August B. Smit, Sabine Spijker, 'me Michel C. Van den Oever*

Sehlooho sena se bile teng e boletsoeng ke lihlooho tse ling ho PMC.

inahaneloang

Medial prefrontal cortex (mPFC) e kenella ka mokhoa o hlakileng mesebetsing e mengata ea kelello, ho kenyelletsa tlhokomelo, taolo ea inhibitory, sebopeho sa tloaelo, mohopolo oa ho sebetsa le mohopolo oa nako e telele. Ntle le moo, ka ho kopanya ho kopaneng ha eona le libaka tse katlasehileng (mohlala, thalamus, striatum, amygdala le hippocampus), mPFC e nahanoa hore e fana ka taolo ea holimo-tlase holim 'a ts'ebetso ea ts'ebetso ea boiphetetso le e khothalletsang takatso. Hobane mPFC e kentse letsoho ts'ebetsong ea mefuta-futa ea maikutlo le maikutlo a fapaneng, ho nahanoa hore e sebetsa e le sebaka se bohareng ho lipontso tsa methapo ea methapo ea methapo ea methapo ea mafu a kelello. Theknoloji e ncha ea optogenetics e nolofalletsa motho ho sebetsa le ho sebetsa ka har'a potoloho ea mPFC ka tharollo ea sebaka le ea nakoana. Sena se fana ka leseli la bohlokoa la tlatsetso ea monehelo oa litlatsetso tse ikhethang tsa neuronal le khokahano ea tsona ho ts'ebetso ea mPFC maemong a bophelo bo botle le a mafu. Thutong ena, re hlahisa tsebo ea hajoale e fumanoeng ka mekhoa ea optogenetic mabapi le ts'ebetso ea mPFC le dysfunction mme re hokahanya sena le liphumano tse tsoang lits'ebetsong tsa setso tsa ho kena lipakeng tse sebelisitsoeng ho etsa lipatlisiso ka potoloho ea mPFC mehlaleng ea liphoofolo le mehlala ea mafu a kelello.

Keywords: optogenetics, preortalal cortex, kelello, khatello ea maikutlo, bokhoba, tšabo, mohopolo

Selelekela

Kutloisiso e qaqileng mabapi le khokahano le ts'ebetso ea ts'ebetso ea methapo ke ea bohlokoa haholo ho utloisisa hore na boko bo sebetsa joang ho bophelo bo botle le bokuli. Medial prefrontal cortex (mPFC) ke tikoloho ea boko e kentsoeng ts'ebetsong ea plethora ea mathata a methapo ea kutlo le kelello. Leha ho le joalo ka nako e telele, ho rarahana ha sebopeho sa hae ho sitisitse lipatlisiso tse ngata tsa tlatsetso ea mefuta e fapaneng ea lisele tsa mPFC le likhakanyo tsa bona tse amanang le ts'ebetso, ho nts'etsopele le polelo ea boitšoaro bo amanang le ho se sebetse hantle hoa kelello. Ka khokahano ea eona e mengata le libaka tse ling tsa cortical le subcortical (Groenewegen et al., ), mPFC e ka sebetsa e le boto ea taolo, e kenyelletsa tlhaiso-leseling eo e e fumanang mehahong e mengata ea ho kenyelletsa le ho fetola tlhaiso-leseling e ntlafalitsoeng ho meaho ea tlhahiso (Miller le Cohen, ). Maemo a mangata a kelello a batho, ho kenyelletsa khatello ea maikutlo, lefu la kelello le tšebeliso e mpe ea lithethefatsi, li hokahane le mosebetsi o fetotsoeng oa MPFC (Tzschentke, ; Heidbreder le Groenewegen, ; Van den Oever et al., ). Sena se ts'ehetsoa ke palo e kholo ea lithuto tsa liteko tsa liphoofolo moo lesapo, ho kenella hoa meriana le ts'ebeliso ea methapo ea methapo ea motlakase li sebelisitsoeng ho bona hore na mPFC e kentse letsoho lits'ebetsong tsa tlhokomeliso le matšoao a mafu a kelello (joalo ka ha ho hlalositsoe ka tlase). Leha ho le joalo, ho arohana ka nepo ha mokhatlo o rarahaneng oa mPFC ho hloka ho kena lipakeng le boemo bo ikhethang ba seleng le tharollo ea nakoana holima subcond timescale. Lilemong tsa morao tjena, palo e eketsehang ka potlako ea lithuto e sebelisitse mekhoa ea optogenetic ho sebetsana le bothata bona, bo ntlafalitseng kutloisiso ea rona ea potoloho ea mPFC. Re tla qala ka bokhutšoaane nalane ea mahlale a morao-rao le menyetla ea lisebelisoa tsa optogenetic mme re tla hlahloba lingoliloeng tse fumanehang tse sebelisang optogenetics ho lahla monehelo oa mefuta e fapaneng ea lisele tsa mPFC, le khokahano ea tsona kahare ho mPFC le libakeng tse ling tsa kelello. mathata.

Theknoloji ea Optogenetics

Mahlale a optogenetics a nka monyetla oa liprotheine tse bobebe tse bobebe tsa tlhaho, tse kang li-opsin tse sa bonahaleng tse kenang ka har'a li-neuron tse sebetsang tsa 'mele, li lumella ho laola mesebetsi ea methapo. a vitro 'me Ka vivo (Boyden et al., ; Deisseroth, ). Mokhoa ona o tšoauoa ke bokhoni ba ho fetolela ho thunya ha neuronal ho millisecond timescale ka mofuta o ikhethang oa mofuta oa lisele ho liphoofolo tse falimehileng, tse tsamaeang ka bolokolohi (Gradinaru et al., ). Opsin e sebelisang ho sebelisa litlolo tse sebelisang matla ka ho fetesisa ke Channelrhodopsin-2 (ChR2; le li-variants tse fetotsoeng liphatsa tsa lefutso), mocha oa li-cation o kenyang ts'ebetso e ka fokotsang matla a bonesitsoeng ka li-pulses tsa leseli le leputsoa (Mattis et al., ). Ka lehlakoreng le leng, pampiri ea chloride halorhodopsin (NpHR) kapa proton pump Archaerhodopsin (Arch kapa ArchT) hangata e sebelisetsoa ho etsa li-membrane tsa methapo ea methapo (Mattis et al., ). Puisano e hlakileng mabapi le ts'ebeliso le bohlokoa ba mefuta e fapaneng ea opsin le lisebelisoa tsa optogenetic li ka fetela ka holimo ho lintlha tsa tlhahlobo ena, empa li hlahlojoe hantle ke ba bang (Zhang et al., ; Yizhar et al., ). Ka bokhutšoanyane, mofuta o ikhethang oa mofuta oa li-opsin o ka fihlelleha ho sebelisoa maano a mabapi le liphatsa tsa lefutso (Zhang et al., ). Liphoofolo tsa Transgenic le likokoana-hloko li haha ​​mefuta e tsamaisang opsin tlasa taolo e tobileng ea tatellano e khethehileng ea morekisi e etsa hore polelo ea li-opsin ka mefuta ea lisele tse hlalositsoeng (sheba leqephe la tlatsetso la S1 bakeng sa kakaretso ea manolo a optogenetic a tšohliloeng tlhahlobisong ena). Ntle le moo, polelo ea ho khetha sele e ka fumaneha ka ho sebelisa mela ea mokhanni oa "mouse-rat" kapa "Cre-recombinase" (Cre) e kopantsoeng le li-veisin tsa opsin tse itšetlehileng ka mefuta ea tsona. Mabapi le li-neurons tsa thabo ea "pyramidal" tse teng ho mPFC, morekisi oa CaMKIIα kapa Thy1 a ka sebelisoa ho hlahisa li-opsin ka liseleng tsena (Gradinaru et al., ; Van den Oever et al., ). Ha bana e le barekisi ba matla, ba loketse ho tsamaisa polelo ea mofuta oa opsin o behiloeng tlase nokeng ea morekisi. Libaka tsa Promoter tse sebelisetsoang ho lebisa li-interneuron tsa GABAergic hangata ha li khothatse haholo, ka hona ho feto-fetoha ha ts'ebetso ea maqhubu a mPFC hangata ho fihlelleha ho sebelisoa litoeba tsa transgenic tseo ho tsona morekisi ea ikhethang oa sele ea GABAergic a tsamaisang polelo ea Cre (Zhang et al., ). Mohlala, ho sebelisa li-interneuron tse potlakileng ka potlako tsa li-GABAergic, parvalbumin (PV) :: Lice litoeba tsa cre li sebelisoa haholo (Sohal et al., ; Sparta et al., ). Ha liphoofolo tsena tsa transgenic li amohela veter ea vaerase eo ho eona mofuta oa opsin o kentsoeng ka har'a mohala o bulehileng o buloang ka mokhoa o bulehileng, lisele tse hlalosang ka mokhoa o hlakileng li ke ke tsa fetohela sebopeho se bulehileng sa ho bala ho nolofalletsa polelo ea opsin e tsamaisoang ke morekisi ea sebetsang ka mokhoa o hlakileng (mohlala, elongation factor) 1cy; EF1α promoter) (Zhang et al., ).

etsoe Ka vivo liteko, leseli le ka tsamaisoa bokong ka sesebelisoa sa laser kapa sa LED se kopantsoeng le fiber e nyane ea sefahleho (~ 100-300 μm) e kentsoeng bokong 'me e etselitsoe lisele tsa opsin tse hlalosang (Sparta et al., ). Mofuta oa opsin o sebelisitsoeng le botebo ba lithane tse khantšitsoeng li bontša matla a waveluth le mohloli o nepahetseng oa leseli o hlokahalang. Ntle le ho feto-fetoha ha molumo oa opsin o hlalosang somata, ho qhekella ka mokhoa o ikhethileng hoa khoneha ka ho bonesa opsin e bonts'a likhakanyo tse sebetsang sebakeng se reretsoeng ho tsejoa (Zhang et al., ). Melemo e meng e kenyelletsa ho fetoha hape ka potlako le ho pheta-pheta ha photostimulation, ho hokahana le lirekoto tsa electrophysiological le tatomical trope tse sebelisang liprotheine tsa fluorescent tse sebelisitsoeng ho li-opsins (Gradinaru et al., ). Meeli ea bohlokoa e lokelang ho nahanoa ke chefo ea livaerase tsa vaerase le ho futhumala ho kotsi ha li-neuron nakong ea ho fetoha ha moea. Leha e na le meeli e fokolang, mekhoa ea optogenetic e na le bokhoni bo sa lekanyetsoang ba ho khetha mesebetsi ea neuronal ea MPFC ka litekanyetso tsa boits'oaro le litokisetso tsa boiketsetso tse bobebe (Yizhar et al., ). Ha boholo ba liteko tse phatlalalitsoeng tsa optogenetic tse ntseng li etsoa hona joale li entsoe ka litoeba le likhoto, re tla shebana haholo le ts'ebetso ea "methapo" ea "pent" ea methapo ea methapo.

Anatomy

Kahare ho mPFC, ho hlalositsoe libaka tse 'ne tse arohaneng ho theosa le sebaka sa ho kenella, ka ho re sebaka sa medial precentral (PrCm; se tsejoang hape e le sebaka sa bobeli sa bokapele (Fr2), sebaka sa pele sa "cortex" (ACC), "cortex" ea pele. PLC) le infralimbic cortex (ILC; Heidbreder le Groenewegen, ). Ntle le karohano ena, e thehiloeng haholo ho phapusing ea cytoar, mPFC e lula e arotsoe likarolo tsa dorsal (dmPFC), e kenyeletsang ACC le sebaka sa dorsal sa PLC, le karolo e kenang (vmPFC), e akaretsang ventral PLC, ILC le dorsal peduncular cortex (DPC), ho latela maemo a sebetsang le khokahano le libaka tse ling tsa boko (Heidbreder le Groenewegen, ). Molemong oa tlhahlobo ena, likarolong tse latelang re tla shebana haholo le bopaki ba sebopeho se hlahisitsoeng ka lisebelisoa tsa optogenetic, 'me re bue ka ho qaqea ho nepahala ha mPFC ha tlhahisoleseling ena e fumaneha, kapa ho seng joalo sheba ho dmPFC le vmPFC.

Boiphihlelo ba polokeho ea MPFC

Khokahano ea lehae ea mPFC e na le lisele tse hlasimolohileng tsa "pyramidal cell" (80-90% ea palo eohle ea batho) le inhibitory GABAergic interneurons (10-20% ea palo eohle ea batho), bobeli ba bona ba ka arohanngoang hape ka mefuta e fapaneng ea sele ho latela morphological, mmele le molek'hule (Ascoli et al., ; DeFelipe et al., ). Li-subtypes tse ithutoang hantle tsa GABAergic interneuron li kenyelletsa li-interisuratic tse lebisang tlhokomelo e potlakileng ea spiking parvalbumin (PV), le li-interenduron tse lebisang tlhokomelo ea somatostatin (SOM). Li-interneurons tsa PV li khahloa haholo ke lingaka, kaha lipalo tsa tsona li tsejoa li fokotsehile ho bakuli ba lefu la kelello (le tšohliloeng ka tlase) (Beasley le Reynolds, ; Lewis et al., ). Mefuta ka bobeli ea li-interneuron e fana ka taolo e matla holim'a potoloho ea lehae, kaha e khona ho hokahanya mosebetsi oa spiking oa lisele tsa pyramidal tse hlahisang li-neuronal oscillations (Kvitsiani et al., ). Khetho ea lifoto tse khethiloeng tsa maqhubu a PR2-expression PV le SOM ho mPFC ea litoeba e bontšitsoe ho hlahisa likarabelo tse fapaneng tsa potoloho (Kvitsiani et al., ). Li-neuron tsa Parvalbumin li ile tsa fumanoa li laola liphetho tsa li-neuron tse ka sehloohong tsa piramite, kaha li ne li sebetsa ka potlako, ka matla le ka seaparo se tšoanang ho thunya ea mantlha ea sele (Kvitsiani et al., ; Sparta et al., ). Ka lehlakoreng le leng, li-neuron tsa Somatostatin li ile tsa hlophisa phetoho eo li-neuron tsa mantlha tsa pyramidal li ileng tsa e fumana le phello ea ho thibella ha methapo ea kutlo ea li-neuron tsena e ne e fokola, e fetoha ebile e le telele ka nako e telele (Kvitsiani et al., ). Mekhoa ea Optogenetic e netefalitse tlatsetso ea bohlokoa ea GABAergic interneuron ea ho thunya ho oscillations ea gamma le boitšoaro ba maikutlo (Vertes, ; Cruikshank et al., ; Yizhar, ; Nyane le Carter, ). Li-neuron tsa "Pyramidal" kahara V (bona ka tlase) tsa mPFC li ka tšoauoa e le masapo a maholohali, lisele tse sebetsanang ka boqhetseke le lisele tse tšesaane tse its'oereng hantle (Dembrow le Johnston, ). Optogenetic modulation e senoletse hore lisele tse sebetsanang ka boqhetseke li khetholla li-subtypes ka bobeli mme li bonts'itse hore li-interneurons tsa PV li khetha ho etsa merero e meng e sa sebetseng ea "pyramidal neurons" (Lee et al., ). Li-subtypes tsa "cell" tsa Pyramidal li ka khetholoha ho latela polelo ea "dopamine D1 kapa dopamine D2 receptor (D1-R le D2-R), eo li-neurons tsa D1-R li kentsoeng taolo ea taolo ea lijo ka ts'ebetso ea optogenetic e khethiloeng ea sechaba sena ( Land et al., ).

Meralo le khokahano ea mPFC

Mokhatlo oa laminar oa rodent mPFC o fapane hanyane le oa libaka tse ling tsa cortical, tse nang le karolo e ikhethileng ea karolo ea IV (Uylings et al., ). Merero e metle ea li-cortices tsa granular ho ea libakeng tse subcortical e hlaha ho tloha kamoreng e tebileng ea V le VI, 'me likhokahanyo tsa granular cortico-cortico li entsoe haholo ke li-neurons tse karolong e holimo ea II le III (Douglas le Martin, ). MPFC ea rodent leha ho le joalo e haelloa ke mofuta oa phallo ea IV (Uylings et al., ). Ntle le moo, likarolo tse tebileng tsa MPFC tse tebileng le tse fetelletseng li fumana lipehelo tse telele ho tloha libakeng tsa cortical le subcortical le projeke ho ea ho tse ling (limbic) (Sesack et al., ; Gabbott et al., ; Hoover le Vertes, ).

Mokhoa oa laminar o na le liphetho tsa bohlokoa bakeng sa ts'ebetso ea matšoao ho mPFC. Likhakanyo tse fapaneng tse simolohang ho tsoa libakeng tse nang le maoto le mafolofolo li shebile likarolo tsa I le II / III (Romanki et al., ). Bakeng sa nako e telele, mathata a mahlale a sitisitse likhokahano tsa khokahano e sebetsang, joalo ka ha ho kopanngoa ha lesapo la mokokotlo le mokokotlo oa li-axonal ha ho hlile ha ho na khokahano e sebetsang 'me lirekoto tsa paired ha li lokele ho hlahlojoa likhokahano tse telele (Petreanu et al., ). Ntle le moo, lipehelo tse ngata tse telele tse thabisang li kenngoa ka meqomong e matla, e sitisang litekanyo ka tšusumetso ea motlakase. Ts'ebetso ea Optogenetic ea ChR2-e hlalosang libaka tsa presynaptic e bontšitse hore karolo ea II PLC pyramidal neurons e fumane lipallo tse sebetsang ho tsoa ho konteraka ea mPFC, midline thalamic nucleus (MTN), basolateral amygdala (BLA), le ventral hippocampus (HPC; Little and Carter, ). Li-fiber tsena li ile tsa kenella libakeng tse fapaneng tsa dendritic, tseo hangata li neng li boletsoe hampe ke anatomy feela, 'me khokahanyo e bontšitse leeme bakeng sa palo ea batho ba phallo ea bophahamo bo ikhethang (Little le Carter, ). Joalokaha bophahamo ba mokokotlo o khothalelitsoe ho hokahana le matla a nyakallo a morao-rao a morao-rao (EPSC; Humeau et al., ), khokahano ena e hlophisitsoeng hantle ebile e sebetsa hantle e beha boemo ba mPFC ho kopanya le ho fetisetsa tlhahisoleseling ho tsoa mehloling e ikhethileng. Ka bobeli dmPFC le vmPFC li hokahane haholo le thalamus (Gabbott et al., ; Vertes, ). Khokahano ea Thalamocortical e bohlokoa bakeng sa mekhoa e kopanyang ea maikutlo, kutloisiso le letsoalo (John, ; Alitto le Usrey, ). Ntle le ts'ebetso ea thalamic e amoheloang ke li-neurons tsa II (Little le Carter, ), li-neuron tsa thalamic tse arohanang le mokoloto oa mPFC I le tsona li khethollotsoe ka optogenetics (Cruikshank et al., ). Photostimulation ea thalamocortical projeke e qalileng ho tloha bohareng le paralaminar thalamic nuclei e ile ea khanna likarabo tse potlakileng le tse matla tsa mokokotlo oa li-interneuron tsa morao-rao tsa spiking, tse neng li nyakaletse haholo ho feta lisele tsa pyramidal (Cruikshank et al., ). Likhetla tsena li ne li khona ho tsamaisa phepelo ea lisele tsa mmele tsa II / III tsa phiramidi (Cruikshank et al., ). Ka lehlakoreng le leng, ts'ebetso ea pharmacological ea mokokotlo oa I Iocortical interneurons e sebelisang cholinergic agonists ha ea ka ea susumetsa tšireletso ea pele-pele (Christophe et al., ). Ntle le moo, likarabo tsa synaptic tsa li-interneurons tsa mPFC li ile tsa lula li ntlafalitsoe ka mokhoa o pheta-phetoang oa lifoto tsa thalamocortical (Cruikshank et al., ). Liphumano tsena tsa optogenetic li fana ka maikutlo a hore li-neurons tsa "thalamocortical proion neurons li khona ho tsamaisa phetisetso ka nako e telele (metsotso), e hlokahalang bakeng sa ts'ebetso ea memori e sebetsang (e tšohliloeng ka tlase).

Likarolo tse tlase tsa mPFC le tsona li kopantsoe hape (Heidbreder le Groenewegen, ). Khokahano lipakeng tsa ILC le PLC e lekiloe ka mekhoa ea ho batla le morao tjena le lisebelisoa tsa optogenetic (Vertes, ; Ji le Neugebauer, ). Ji le Neugebauer ba bonts'itse hore ho nka lifoto tsa lisele tsa phiramide ea ILC ho fokotsitse tšebetso ea ho itšireletsa le ho tsosa lisele ho PLC lisele tsa piramite, mohlomong li kopantsoe ke phepelo ea pele ho nako (Ji le Neugebauer, ). Ka lehlakoreng le leng, ts'ebetso ea ho ikatisa le ea bohanyetsi ho ChR2 e hlalosang tšebetso e tebileng ea ILC pyramidal neuron e ile ea eketseha hodima ts'ebetso ea mahlo ea bongata bona ba neuronal, ntle le ho ama boitšoaro ba ILC ba inhibitory neuron spiking (Ji le Neugebauer, ). Ha morero oa ILC le PLC o fapana ka holim'a boko mme o na le likarolo tse fapaneng lipakeng tsa mekhoa e mengata, ho kenyelletsa boitšoaro bo tloaelehileng, polelo ea tšabo le boits'oaro bo matla (Killcross le Coutureau, ; Vertes, ; Van den Oever et al., ; Sierra-Mercado et al., ), mochine ona o ka lumella ILC ho thibela tlhahiso ea PLC, ha ka nako e tšoanang e ntse e kenya ts'ebetsong likarolo tsa eona tse ka sehlohlolong.

MPFC e sebetsa haholo ho likarolo tse ling tsa boko le bokhoni ba eona, bo bo nolofalletsang ho laola mesebetsi ea pono, boiketsetso, litho tsa letsoho le kelello (Miller le Cohen, ; Hoover le Vertes, ). Boithuto ba ho shebella bo bonts'itse phetoho ea dorsoventral hammoho le mPFC ho tloha libakeng tsa sepheo sa dmPFC ho ea ho li-legic target tsa vmPFC (Sesack et al., ; Hoover le Vertes, ). Merero ea Glutamatergic ea mPFC ho konokono ea nucleus accumbens (NAc) le khetla li hlalositsoe hantle mme li netefalitsoe ke mekhoa ea optogenetic (Britt et al., ; Suska le al., ). Ho khahlisang ke hore ka microinjection ea moetsi oa tšebeliso ea marang-rang ea ChR2 AAV ho Dlxi12b :: Cre mice, Lee et al. () e fane ka bopaki ba boteng ba li-neurons tsa mPFC GABAergic tse nang le lipakanyo tsa nako e telele ho NAc. Sena se bontša hore ha se li-neuron tsohle tsa GABAergic tse lulang mPFC ke li-Intneurons tsa lehae. Ntle le moo, likhakanyo tsa PLC tsa glutamatergic ho BLA li ithutile li sebelisa theknoloji ea optogenetics. Tsela ena e nahanoa e le ea bohlokoa bakeng sa ho kopanya ts'ebetso e phahameng ea kelello le likarabelo tsa maikutlo tsa kahare (Yizhar, ), ketsahalo e sa sebetseng khatellong ea maikutlo (e koahetsoeng ka lintlha tse ngata ka tlase). Nyane le Carter () optogenetically e lebelletse sekhechana sa PLC sa bobeli mme ea tsebahala lisele tse peli tse ikhethileng tsa "cell piramidal" tse kahare molekong ona tseo e ka bang projeke ea mPFC ea selekane kapa BLA. Li-neuron tsena tsa projeke ea PLC li ne li tšoana ka thepa ea 'mele le' mele, li etsa liteko tse thata tsa mosebetsi oa potoloho. Photostimulation ea contropateral mPFC kapa BLA ChR2-e hlalosang li-presynaptic tse emisitsoeng ka liteishene tsa lisele tsa mPFC kapa BLA tse hlahisang li-pyramidal neurons li bonts'itse hore BLA ho BLA-projeke ea neuron ea PLC e bonts'itse khokahano e matla ea synaptic. Khokahano ea ntlafatso ea synaptic tseleng ena e ne e hokahanngoa le letsoalo le matla la lesapo la mokokotlo, sepheo se seholo sa lesapo la mokokotlo le ho lebisoa ho tsona. Ntle le moo, litlatsetso tsa BLA li lebisitse lits'oants'o tse haufi le soma ea li-neuron tsa PLC-BLA, tse ileng tsa khona ho hlahisa li-EPSC tse matla ho feta likhakanyo tse lebisitsoeng ho dendrite (Little le Carter, ). Litabatabelo tsa PLC-BLA li boetse li shebile karoloana ea li-interneuron tsa GABAergic ho BLA, eo maemong a mang e ileng ea baka tšitiso ea phetoho ea phepo ea GABAergic (Hübner et al., ). Khokahano ena e ikhethileng pakeng tsa PLC le BLA e ka etsa hore puisano e tataisehang e sebetsanang le litekanyetso tse peli, e leng ea bohlokoa bakeng sa taolo e holimo-tlase ea ho araba maikutlo a susumetsang maikutlo.

Patlisiso tsena tsa pele li bonts'a menyetla e ikhethang ea optogenetics ea ho etsa lipatlisiso tsa potoloho ea mPFC maemong a lisele ka bonngoe, khokahanyo ea intra-mPFC le lipakanyo tsa nako e telele le tse amanang le tsona. Photostimulation litokisetsong tse ntle tsa selae ke mokhoa o nepahetseng haholo oa ho hokahanya likhokahano tse sebetsang le ho lekanya thepa ea synaptic lipakeng tsa palo e fapaneng ea methapo ea methapo. Leha ho le joalo, ho fumana hore na khokahano e itseng e kenella ka mokhoa o hlakileng ts'ebetsong e hlalositsoeng ea kelello, Ka vivo modulation ea mesebetsi ea neural ea hlokahala. Likarolong tse latelang, re tla tšohla lintho tse fumanoeng ho tsoa lipakeng tsa optogenetic ho liphoofolo tse tsamaeang ka bolokolohi.

Temoho

Mekhoa ea ho laola ka moetlo e ts'oaretse mPFC maemong a fapaneng a fapaneng a mesebetsi ea kelello, eo ho eona ho sebetsa le ho hopola nako e telele, ho ba hlokolosi le boits'oaro bo seng bo ntse bo rarollotsoe ke theknoloji ea optogenetics.

Ho sebetsa ts'ebetso ea ho hopola, ho falimeha le taolo ea nakoana

Ho hopola ho sebetsa ke ts'ebetso e rarahaneng ea ts'ebetso ea boko e bolelang poloko ea nakoana ea tlhahisoleseling (nako ea metsotsoana ho isa ho metsotso) e hlokahalang bakeng sa ts'ebetso ea kelello (Baddeley, ). MPFC e kentse letsoho ts'ebetsong ena kaha ho ile ha fumaneha hore ts'ebetso e nchafalitsoeng ea meriana le ts'ebetso ea ts'ebetso ea ts'ebetso ea PLC e senyehileng (Gilmartin le Helmstetter, ). Ts'ebetso ea mohopolo oa ho sebetsa e ka hlahlojoa ho sebelisoa ts'ebetso ea ho tšosa tšabo, eo ho eona ts'usumetso e nang le maemo e lateloang ke ts'usumetso e matla ntle le tšitiso kamora ho lieha metsotsoana e mmalwa. Li-neuron tsa pele li tsejoa ho bonts'a ho thunya ho sa khaotseng nakong ea ho lieha (Gilmartin le McEchron, ), ho fana ka maikutlo a karolo bakeng sa mPFC ho boloka kemiso ea tšusumetso e nang le boemo nakong ea ho lieha. Leha ho le joalo, bopaki bo bakang ho hloka hoa ts'ebetso ea methapo ea mPFC ho tiisa ho lieha ho fanoe feela ka ts'ebeliso ea optogenetic. Gilmartin et al. () e hlalositse ArchT ka li-neurons tsa PLC (e sebelisa papatso e se nang khetho ea CAG) ho lumella thibelo ka ho khetheha nakong ea ho lieha ha mosebetsi oa ho fumana tšabo. Ho joalo, Photoinhibition nakong ea ho lieha ho ithuta ha mokhatlo o lipakeng tsa tšusumetso e se nang letho, e netefatsang hore spark ea neuron ea PLC e ea hlokahala bakeng sa ts'ebetso ea ts'ebetso ea memori nakong ea ho ts'oara maemo a tšosang. Mosebetsi o fapaneng oa ho lekanya ts'ebetso ea mohopolo oa ho sebetsa ke mosebetsi o liehang ho fetoloa, oo ho oona liphoofolo li sebelisang mochine oa khatiso oa lever ka tebello e reretsoeng ho fumana moputso (Dunnett et al., ). Lits'oaetso tse tlisoang ke "Exitotoxic" le "inptivation" ea mPFC e senyehileng ka kotloloho e fumanehang le polelo ea mosebetsi o liehang oa ho fetoloa ka ho lieha ha nako, ho bontša hore ts'ebetso ea MPFC e bohlokoa ha tlhokahalo ea memori e sebetsa (Rossi et al., ). Manonyeletso a "ventral striatum" kapa "dorsal hippocampus", libaka tse hokahane haholo le mPFC, ha lia ka tsa lebisa ho fokotseng ts'ebetso ea phetoho e liehang. Habohlokoa, ts'ebetso ea ChR2-mediated activation ea li-interneurons tsa PV ho PLC ka boikhethelo nakong ea ho lieha e boetse e sitisa ts'ebetso e kholo mosebetsing ona (Rossi et al., ). Ka kopanelo, lithuto tsena li bonts'a hore ts'ebetso ea PLC e ea hlokahala bakeng sa ts'ebetso ea ho sebetsa ea memori mme e bonts'a hore ts'oaetso ea lifoto tsa li-interneurons tsa PV li ka etsisa litlamorao tsa lesion le sa foleng tsa kemiso ea meriana ka mokhoa o nepahetseng oa nakoana.

Ts'ebetso ea mohopolo ea sebetsang ea mPFC e fetoloa ke mekhahlelo e mengata ea monoamine, ho kenyelletsa le sistimi ea noradrenaline le dopamine (DA) (Rossetti le Carboni, ; Robbins le Roberts, ). Nakong ea mohopolo oa ho sebetsa ka nako, lintlha tsa extracellular noradrenaline li eketseha ho mPFC le ts'usumetso ea litheko tsa meriana ea alpha-2A adrenoreceptors ho PLC e ntlafalitseng ts'ebetso ea memori e sebetsang (Rossetti le Carboni, ; Ramos et al., ). U sebelisa optogenetics, ho ile ha fumaneha hore ts'ebeliso ea khanya ea ChR2 e hlalosang Noradrenergic e tsoang ho locus coeruleus e tsosetse ho thunya ho sa khaotseng, sehokelo sa cellular sa memori e sebetsang, ho PLC le ACC pyramidal neurons, e neng e kopantsoe ka ts'ebetso ea presynaptic alpha1 le postsynaptic alpha2 et al., ). Cortical noradrenaline ha e ea ameha feela tšebetsong ea mohopolo oa ts'ebetso, empa ho lumeloa hore e lumellana haholo le libaka tsa tlhokomelo, ho tsosa le ho tsosa (Berridge, ). Carter le al. () o sebelisitse ts'ebetso ea optogenetic ho tsosa phetiso ea noradrenaline hantle le ho ithuta tšusumetso ea eona tlhokomelong ea litoeba. Leseli la NpHR le hlalosang locus coeruleus noradrenergic neurons le ile la fokotsa ho tsoha nakong ea phoofolo 'me la baka phokotso ea li-extracellular noradrenaline level ho mPFC. Tumellanong le sena, tonic and phasic photostimulation of ChR2-expression locus coeruleus neurons e hlahisitse phetoho ea kapele ea ho robala le ho tsoha. Ho khahlisang ke hore ts'ebetso ea tonic e ekelitse ts'ebetso e akaretsang ea basebetsi, athe ts'ebetso ea phasic e bile le phello e fapaneng. Ho feta moo, ts'ebetso e matla ea maqhubu a phahameng (> 5 Hz) ea locus coeruleus neurons e hlahisitse boemo ba ho ts'oaroa ha boitšoaro. Carter le al. () bonts'a hore phello ena ea morao e kanna ea ts'oaroa ke ho putlama ha mabenkele a mPFC noradrenaline, joalo ka ha nako e telele ea photostimulation e fokotsehile maemo a feteletseng a Noradrenaline MPFC, 'me ho ts'oaroa ka boits'oaro ho amoheloe ho tlatselitsoe ke Noradrenaline reuptake inhibitors. Boithuto bona bo khahlisang bo bontša hore tokollo ea mantlha ea oradrenaline e entsoe hantle hore e susumetse tsoho, le liphapang tse poteletseng li bile le litlamorao tse kholo phetohong ea boroko le ho tsosa.

Ho hopola ho sebetsa hangata ho nkuoa ho emisa memori ea maikutlo a mabeli a arotsoeng ke ho lieha. Ho ts'oara nako kapa ho hopola nako ka nako e hlalositsoeng ka nako ea metsotsoana ho nahanoa hore ho kenyelletsa ts'ebetso ea nako e kahare ea nako, eo ho eona lipallo tsa mPFC le tsona li kentsoeng (Kim et al., ). Haholo-holo, phetisetso ea DA ho mPFC e kentse letsoho nakong ea nako ea nakoana e hlalositsoeng e sebelisang mosebetsi oa nako ea nako ea nakoana (Drew et al., ). Phuputsong ea morao tjena, phetisetso ea D1-R ho mPFC e bonts'itsoe e nkile karolo ea bohlokoa taolong ea nakoana ea motsamao o lebisang pakaneng (moputso) nakong ea nako e hlalositsoeng (Narayanan et al., ). Pharmacological blockade ea D1-R, empa eseng D2-R ho ILC le taolo ea nakoana ea tempro ea PLC mabapi le ho arabela mosebetsing oa nako e tsitsitseng oa nako. Ho ts'ehetsa karolo e tobileng ea D1-Rs, NpHR-mediated optical inhibition ea mPFC D1-R e hlalosang li-neurons tse sitisang ts'ebetso ea nako ea nakoana (Narayanan et al., ). Ka mokhoa o makatsang, chR2-Mediated susumetsang ea li-neuron tsa D1-R nakong ea 10 s ea nako e telele ea 20-s e ntlafalitsoeng e arabela feela ho 20 s. Ho ipapisitse le bopaki bona, bangoli ba pheha khang ea hore sisteme ea mPFC D1 e laola taolo ea nakoana ea boits'oaro bo lebisitsoeng ho e-na le tšebeliso ea nako ea nako.

Leha ho na le tsoelo-pele e ntle lilemong tsa morao tjena, ho sa na le ho hongata ho lokelang ho ithutoa mabapi le ts'ebetso ea methapo ea kutlo ea kelello le mesebetsi e amanang le eona ka ho bapisa ho kenella ha mPFC optogenetic mesebetsing e fapaneng ka har'a phoofolo e le 'ngoe. Sena ke sa bohlokoa ho, mohlala, ho lekola ho tšoana le ho se tšoane ha mPFC mekhatlo e laolang nako le nako ea ho sebetsa ha memori. Ho thunngoa ka nepo ha mPFC D1 neurons mediates taolo ea nakoana ea sepheo se lebisitsoeng ho arabela, empa hore na (ts'ebetso e tsitsitseng) ea bongata bona ba neuronal le eona e hlokahala bakeng sa ts'ebetso e ntle ea ts'ebetso ea mohopolo e sa ntseng e lokela ho ithutoa (Narayanan et al., ; Gilmartin et al., ). Ntle le moo, le ha mekhoa ea ho sebelisa hampe e bontša hore sistimi ea mPFC cholinergic e na le karolo ea bohlokoa mohopolong oa tšebetso (Chudasama et al., ), kahare ho mPFC, tsamaiso ea methapo ena ha e so ka e tobisoa ka kotloloho ke theknoloji ea optogenetics.

Ho ithuta, ho hopola le ho timela

MPFC e nahanoa hore e fana ka taolo ea kelello mabapi le maemo a arabelloang le boiphetetso bo khotsofatsang ka ho kopanya leseli mabapi le maemo le liketsahalo tse nang le boiphihlelo (Euston et al., ). Paradigm ea boemo bo tšosang ke mofuta oa phoofolo o sebelisoang haholo ho ithuta ho ithuta le ho hopola, hammoho le ho fela hoa mehopolo e fumanoeng ea tšabo (LeDoux, ; Milad le Quirk, ; Maren et al., ). Karolo e ikhethileng ea li-subareas tsa mPFC e se e thehiloe polelo ea maemo a tšabo ea maemo a tšosang, ka libaka tse kenellang hare ho kenyeletsa ho kenyeletsa le polelo ea memori ea tšabo le libaka tse kenang ka hare ho naha ho kenya letsoho ho kopaneng le ho hlahiseng mohopolo oa ho timela (Petros et al., ; Lekhotla et al., ). Liphumano tsena li tšehetsoa ke liso, inactivations ea meriana le Ka vivo Lirekoto tsa spike (Morgan le LeDoux, ; Milad le Quirk, ; Lekhotla et al., ). Leha ho le joalo, lipatlisiso mabapi le tlatsetso ea nakoana ea likarolo tse itseng tsa potoloho ea mPFC li sa tsoa qaloa haufinyane. U sebelisa optogenetics, Courtin et al. () e thehile hore phasic inhibition ea dmPFC PV interneurons e ts'ehetsa polelo ea ts'abo, joalo ka ha e lekotsoe ka boitšoaro bo sa tsitsang ho paradigm ea maemo a tšosang. Ba bonts'a pele hore ts'ebetso ea karoloana e nyane ea li-interneuron tsa GABA e thibetsoe nakong ea tlhahiso ea ts'usumetso e nang le maemo e amanang le ho tsitsipana maoto. Ka mor'a moo, ts'ebeliso ena e ile ea bonoa e le li-interneurons tsa PV, kaha ChR2- le ArchT-mediated optical modulation of PV neurons, ka ho latellana, polelo e tlatselletsang kapa e tsitsitseng ea tšabo e nang le maemo. Ho makatsang ke hore, thibelo ea "optic" ea "neurons" ena e boetse e tsosa boitšoaro ba leqhoa pele ho boemo bo nang le tšabo le polelo e khutliselitsoeng ea tšabo kamora thupelo ea ho timela (Courtin et al., ). Ba fumane hore karabelo ea PV ea neuron e laoloang ke tšabo e kopantsoe le ho khutlisetsa likarolo tsa "theta phase oscillations" mPFC le disinhibition ea lisele tsa "pyramidal" tse kenang ho BLA, le ho ts'ehetsa karolo ea morero oa mPFC-BLA taolong ea maikutlo. Phuputso ena e boetse e bonts'a sechaba sa bobeli sa li-interneuron tsa inhibitory tse bonts'itseng ts'ebetso e eketsehileng nakong ea maemo a tšabo. Bangoli ba hakanya hore tšebeliso ena e kanna ea thibela li-interneurons tsa PV mme ea amohela tlhahiso ho tsoa libakeng tsa boko (mohlala, hippocampus, BLA) e tsamaisang polelo ea tšabo (Courtin et al., ), mohopolo o khahlisang o sa ntseng o lokela ho rarolloa ke lipatlisiso tsa nako e tlang. Ho felisoa ha tšabo e nang le maemo ho amana le ts'oaetso e fokotsehileng ea phetisetso ea mPFC ho lisele tsa BLA pyramidal, empa ha ea ka ea ama tlhahiso ea lisebelisoa tsa GABAergic BLA le lisele tse kopaneng, joalo ka ha ho bonts'oe ho sebelisa optogenetics (Cho et al., ). Ka lebaka leo, ho leka-lekana / ho sitisoa (E / I) tseleng ena ho ka fetoloa, ho rata inhibition mme ho fella ka khatello ea karabelo e nang le tšabo (Cho et al., ). Lithuto tsena tsa optogenetic li netefatsa karolo ea dmPFC ho khanna likarabo tsa tšabo le ho nchafatsa tlatsetso ea nakoana ea litlatsetso tsa li-interneurons tsa GABAergic ka boitšoaro bona. Boithuto bo khahlisang ke Lee et al. () e bonts'itse hore ts'ebetso ea lifoto tsa lipakanyo tsa nako e telele tsa Gabaergic mPFC ho NAc e entse hore ho qojoe libaka tsa 'nete, ho fana ka maikutlo a hore tsela ena e nyane e ka laola ho arabela ho susumetsang ha maikutlo.

Boitšoaro ba tloaelo

Mekhoa e metle e hlalosoa e le mekhoa ea boits'oaro e sa nahaneleng liphetoho meralong ea sephetho. Boitšoaro ba tloaelo bo laoloa ka mokhoa o fapaneng ke li-mPFC subareas; athe PLC e khothaletsa ho tenyetseha, ts'ebetso ea ILC e thibela maemo le ho ntlafatsa boits'oaro bo bobe (Killcross le Coutureau, ). Liphuputso tse fetileng li bonts'itse hore lesion le ts'ebetso ea meriana ea ILC e etsa hore ho be le phetoho ea ho araba ka mokhoa o hlakileng (Coutureau le Killcross, ). Taolo ea nakoana ea li-neuron tsa ILC ho tloaelo ea boits'oaro e netefalitsoe le ho ntlafatsoa ke phetoho e pheta-phetoang ea optogenetic. Photoinhibition e khuts'oane ea lisele tsa piramite ea ILC e thibetse sebopeho le polelo ea boits'oaro, empa karabelo e latelang ea boits'oaro e ne e itšetleha ka nako ea thibelo (Smith et al., ; Smith le Greybiel, ). Lithutong tsena, boits'oaro bo tloaelo bo ile ba hlahlojoa ka lithupelo tsa koetliso ho fumana moputso mosebetsing oa T-maze o khahliloeng. Kamora ho phenya-phenya, likhoto li ile tsa hana ho amohela moputso. Liphoofolo li ile tsa tsoela pele ka mokhoa o tataisoang ke sepheo ha lisele tsa piramite ea ILC li ne li khutsisoa ka mokhoa o phethahetseng nakong ea ho theha tloaelo, empa hang ha mokhoa ona o hlahisitsoe ka botlalo, ts'ebetso ea lifoto e ile ea tsosa mokhoa o mocha. Ho feta moo, ha ts'ebetso ea lifoto e phetoa nakong ea ts'ebetso e ncha, liphoofolo li ile tsa hlahisa tloaelo ea pele (Smith et al., ). Phetoho ena e potlakileng lipakeng tsa boits'oaro bo tloaetseng e bonts'a hore esita le mekhoa ea semiautomatic e taolong ea cortical ha e ntse e etsoa. Sebaka sa sepheo sa ILC se pakeng tsa phetoho lipakeng tsa mekhoa ha se so ka se bonoa, empa likhakanyo tsa tšebetso ea methati li khahlisa haholo, hobane mokhoa o tšoanang oa ts'ebetso ea spike o ile oa bonoa libakeng ka bobeli kamora hore tloaelo e theoe (Smith le Graybiel, ). Ho latela bopaki bona, bangoli ba khothalelitse hore nts'etsopele ea ts'ebetso ea tloaelo e lekantsoe ke tekanyo ea ts'ebetso ea sensorimotor striatal le tšebetso ea ILC e tsotellang. Ho khahlisang ke likarolo tse ikhethang feela tsa ILC tse ileng tsa etsa mosebetsi oa ho chesa litlhapi ka har'a dorsolateral striatum (Smith le Graybiel, ), e totobatsa tlhokeho ea ho sebelisa mananeo a ho hlophisa ka mokhoa o khethehileng oa tsela hore a ithute ho potoloha ka botlalo.

Mathata a kelello

Optogenetics e fane ka leseli le lecha la ts'ebetso ea mPFC bokong bo phetseng hantle, empa e boetse e sebelisitsoe ho hlakisa lintho tsa neural circry tse kenyelletsang liketsahalo tse amanang le lefu (Steinberg et al., ). Likarolong tse latelang, re tla tšohla hore na makhopo a optogenetic a netefalitse joang, 'me maemong a mang a ntlafalitse likhopolo tsa hona joale tse ikemiselitseng ho hlalosa tlatsetso ea potoloho ea mPFC likhatisong tse fapaneng tsa mafu a kelello, ho kenyelletsa khatello ea maikutlo, schizophrenia le tšebeliso ea lithethefatsi.

ho tepella maikutlo

Mathata a maholo a khatello ea maikutlo (MDD) ke e 'ngoe ea mafu a kelello a atileng haholo, a hakanngoang ho ama hoo e ka bang 5% ea baahi ba lefatše mme ka hona a nkuoa e le sesosa se etelletseng pele sa bokooa lefatšeng ka bophara (Mokhatlo oa Lefatše oa Bophelo, ). Mekhoa e meholo ea tlhahlobo ea Mathata a ho Ferekana e kenyelletsa maikutlo a sithabetsang le anhedonia (ho fokotsa bokhoni ba ho thabela thabo) tse phehellang nako e telele le tse amang boiphihlelo bo bong le bo bong ba bophelo ba letsatsi le letsatsi (American Psychiatric Association, ). Ntle le moo, ts'oaetso ea MDD e kenyelletsa litlamorao tsa somatic, joalo ka ho ferekanya takatso ea lijo (ho theola boima ba 'mele kapa phaello), boroko (boroko kapa hypersomnia), hammoho le maemong a tšebetso ea psychomotor (ho ruruha kapa ho khutla ha mokokotlo). Ho fokotseha hoa kelello ho khetholloang ke ho sitisoa ke ho hopola lintho le ho etsa liqeto, ho lahleheloa ke khatello ea maikutlo le ho tsepamisa maikutlo ho boetse ho nkuoa e le karolo ea mantlha ea ho ntšetsapele mmuso o nyahamisang (Murrough et al., ). Mantsoe a mangata a kopantsoeng le khatello ea maikutlo a tsamaeang le khatello ea maikutlo a hlahisoa ke ts'ebetso e sa sebetseng libakeng tse ngata tsa boko le lipotoloho, ho kenyelletsa le moputso oa boko, litsi tsa botsamaisi le tsa botsamaisi bo phahameng.

Ha mPFC e nkuoa e le setsi sa potoloho e khothalletsang ts'ebetso ea kelello e hlophisehileng haholoanyane mme e fana ka taolo e holimo-tlase holim'a lits'ebetso tse amanang le tsamaiso ea li-limbic system tse amanang le eona (Clark et al., ; Ho phatloha le al., ; Treadway le Zald, ), ho khothaletsoa ho ba le karolo ea bohlokoa ho bosholu bo botle le boloi bo amanang le khatello ea maikutlo. Ho batho, linaha tse sithabetsang li hokahane le ts'ebetso e ka pele e nyarosang (hyper- kapa hypo-activation) le morphology, eo ho nahanoang hore e kenya letsoho ts'ebetsong ea ho hopola likhopolo, taolo e mpe ea maikutlo (anhedonia, e amang hampe), khethollo e lebisang tlhokomelo le ho etsa liqeto tse sa sebetseng ( Southwick et al., ; Fales et al., ; Beevers et al., ; Diner et al., ). Ho pepeseha ha khatello ea maikutlo, ho amanang le ho qala le ho hola hoa boemo bo sithabetsang, ho nkuoa ho le kotsi bakeng sa ts'ebetso ea mPFC. Ts'ebetso e nepahetseng ea mPFC ea hlokahala bakeng sa ho feto-fetoha ha maemo a phetoho a susumetsang khatello ea maikutlo le ho fana ka taolo holim'a libaka tse sebetsanang le khatello ea khatello ea maikutlo (Amat et al., ; Czéh et al., ;; Arnsten, ; Dias-Ferreira et al., ; Treadway et al., ). Lilemong tsa morao tjena, lebokose la lisebelisoa tsa kalafo bakeng sa ho phekola khatello ea maikutlo le atolositsoe ka tšusumetso e tebileng ea kelello (DBS) ea PFC. Lithuto tsena tsa morao-rao li bontšitse hore tšusumetso e sa feleng ea subgenual cingrate cortex (Cg25), e lekanang le motho ka mokhoa oa rodent vmPFC (Hamani et al., ; Chang et al., ), e khutlisetsa bofokoli bo sebetsanang le khatello ea maikutlo ea cortical le ho fokotsa matšoao ho bakuli ba tepelletseng maikutlo ba nang le khatello ea maikutlo (Mayberg et al., ). Boithuto ba morao-rao ba phetolelo bo netefalitse ho kenya letsoho ha mPFC likarabo tse kang tsa khatello ea maikutlo, joalo ka ha moea o matla o fokotsang motlakase oa rat oa PLC o fokolisang boitšoaro bo nyarosang o bontšitsoeng tekong e qobelloang ea ho sesa (FST; Hamani et al., ), e ikamahanya le maemo a susumetsang, a sebetsang ho maemo a phephetsang. Ka mokhoa o ts'oanang, kamora khatello ea maikutlo e sa reroang e sa lebelloang, vmPFC DBS e fokotseng anhedonia e amanang le khatello ea maikutlo, joalo ka ha e hlahlojoa ke teko e ikhethang ea ho rata litheko le ho imoloha boikarabellong ba sechaba ho litoeba tse atamelaneng le khatello ea maikutlo ea khatello ea khatello ea sechaba (Hamani et al., ; Veerakumar et al., ). Ha ba kopantsoe hammoho, ho theosa le lilemo lipatlisiso tsa bo-ralitaba le tsa bophelo ba pele li ile tsa ama mPFC e le mokena-lipakeng oa bohlokoa oa "lipontšo tsa khatello" (Koenigs le Grafman, ), e ileng ea tsosa takatso ea ho etsa lintho ka mokhoa o hlakileng le ho hlakisoa ha liphallelo tsa mPFC le litlatsetso tse hlakileng mabapi le nts'etsopele ea pherekano le karabelo e khahlanong le khatello.

Teko ea pele ea optogenetic e ileng ea lekola ka kotloloho karolo ea ts'ebetso ea mPFC maemong a tepelletseng maikutlong e netefalitse hore ts'ebetso ea li-neuron tsa vmPFC e khutlisa matšoao a kang a nyahamisang bathong ba tlokotsing ea litoeba (Covington et al., ;; Setšoantšo Figure1) .1). Phuputsong ena, bangoli ba sebelisitse paradigm e sa feleng ea ho hloloa ha sechaba, mohlala oa khatello ea maikutlo o nang le sefahleho se phahameng, o nahanang ebile o haha ​​'nete (Nestler le Hyman, ) ho khetholla litoeba mabapi le ho tiisetsa / ho ba kotsing ea khatello ea sechaba. Photostimulation ea vmPFC e fumanoe ho sebelisoa vaerase ea herpes simplex (HSV) veter coding bakeng sa ChR2 e tsamaisoang ke morekisi oa IE4 / 5, e neng e lebisitse ho ChR2 ho li-neurons tsa MPFC ka tsela e sa ikhetheleng (Covington et al., ). Ka ho khetheha, ILC le PLC ea litoeba tse bakang khatello ea maikutlo e ile ea hlohlelletsoa ka mokhoa o ts'oanang le oa paramente ea DBS eo pele e neng e fokotsa matšoao a sithabetsang, a etsisa ho thunya ha cortical (Hamani et al., ). Photostimulation e tsosolositse lintlha tse ngata tsa tšebelisano ea sechaba le ho fokotsa li-anhedonia, joalo ka ha ho bontšitsoe ho khetha ho noa tharollo ea sucrose ka metsi, ntle le ho fetola maemo a matšoenyeho kapa ts'ebetso ea memori ea sechaba (Covington et al., ). Hantle haholo, mananeo a mPFC a setso a lebisitse tlhokomatsong e hanyetsanang. Mohlala, lesapo la mPFC la generic le ile la lebisa ponahalong ea boits'oaro bo sithabetsang, ho kenyelletsa ho hloka thuso ho ithutoang (Klein et al., ), athe inactivation e potlakileng ea bongaka ea ILC e hlahisitse karabelo e felisang khatello ea maikutlo, joalo ka ha e hlahlojoa ke FST (Slattery et al., ). Liphumano tsena tse hanyetsanang li ka tsoa ho qeto e fapaneng ea nakoana ea mekhoa le / kapa libaka tse fapaneng (tse ka tlase) tse hlahlobiloeng, mohlala, mPFC kaofela (Klein et al., ) vs. vmPFC (Covington et al., ) kapa ILC (Slattery et al., ). E le optogenetic activation ea vmPFC ke Covington et al. () e ne e sa qaqisa subtype e itseng, tataiso ea litlamorao tsa ts'usumetso maemong a potoloho e lula e sa rarolloe. Lintlha tsena li ka bonts'a phapang ea ho nka karolo ha mPFC ho bonoang lithutong tsa batho, tse tšehetsang tšebetso e fokolisitsoeng kapa e eketsehang ea libaka tse ikhethileng polelong ea khatello ea maikutlo.

Setšoantšo sa 1  

Bopaki ba optogenetic ba ho kenya letsoho ha mPFC ho boits'oaro bo joalo ba khatello le matšoenyeho. Flash e putsoa: photoinhibition; putsoa e putsoa: khanya ea litšoantšo; ↑ = litlamorao tsa pro-nyenyefatso / matšoenyeho; ↓ = litlamorao tsa khatello ea maikutlo / khatello ea maikutlo. 1Covington ...

Phuputsong e ileng ea latela, Kumar et al. () sehokelo sa "V" pyramidal se ikhethileng seleng e ikhethileng ea PLC ho hlahloba tlatsetso ea tikoloho ena e tlase ea mPFC ho matšoao a kang khatello ea maikutlo. Ho fihlela sena, ho ne ho sebelisoa li-moses tsa Thy1 :: Chr2 litsoelesa ChR2 liseleng tse nang le liphokojoe tse etselitsoeng meaho e meng ea maoto, ho kenyeletsoa sebaka sa "ventral tegmental" (VTA), BLA le NAc. Ho hlohlelletsa hoo e ka bang kahare ho liphoofolo tsa Naïve ho entse karabelo e matla joalo ka litlatsetso, joalo ka ha ho bonts'itsoe ho fokolisang matla ho FST. Ka hona, liphoofolong tse tlas'a mofuta o sa feleng oa tlhaselo ea sechaba, tšusumetso e sa feleng ea lisele tsa pyramidal ea PLC e bakile phello e telele ea ho tšoenyeha ka nako e telele litekong tse phahameng tsa maze (EPM), tlhahlobo ea mantlha ea ho lekola matšoenyeho. Ntle le litlamorao tsa boits'oaro ba ts'usumetso ea PLC, bangoli ba tlaleha ts'ebetso e kopantsoeng ea oscillatory ho lintlafatso tsa PLC tse loantsoeng le li-limbic (VTA, BLA le NAc), ba fana ka bopaki ba litlamorao tse theohileng tsa ts'ebetso ea sele ea piano ea piramite libakeng tse tlasa boikarabello bakeng sa ts'ebetso e amanang le ts'ebetso e amanang le moputso. . Habohlokoa, liphetoho tse tšoanang ho tšebetso ea li-neuronal potolohong ena li hlokometsoe ho bakuli ba sithabetseng maikutlo (Sheline et al., ) hape e ka ba tlas'a litlamorao-li-antidepressant-mPFC DBS bathong (Mayberg et al., ). Ho khahlisang, ho fapana le ts'ebetso ea vmPFC, ts'usumetso ea lisele tsa piramite ea PLC ha e ea ka ea khutlisa mokhoa o hlakileng oa tlhaselo ea boiketlo ba sechaba (Kumar et al., ). Phapang ena e kanna ea hlahisoa ke likarolo tse fapaneng tsa tšusumetso ea maqhubu a sebelisitsoeng kapa mefuta e fapaneng ea sele le li-mPFC tse pakiloeng. Habohlokoa, joalo ka ha fiber ea optic litekong tsena e ne e lebisitsoe ho ChR2 + somata ho mPFC, likhakanyo tse hlakileng tse hlahisitseng litlamorao tse kang tsa antidepressant li ntse li lokela ho khethoa ke sepheo se tobileng sa morero.

Warden et al. e hlahlobe karolo ea li-efferents tsa mPFC ho boits'oaro bo nyahamisang, ka ho shebella merero ho "dorsal raphe nucleus" (DRN) le hamorao habenula (LHb; Warden et al., ), libaka tse ikhethileng haholo ho MDD (Sartorius et al., ; Lisa Smith ; Albert et al., ; Mahar et al., ). Morero oa mPFC-DRN o khahla haholo, hobane phello ea antmepressant ea vmPFC DBS ka likhoto e tsamaisana le liphetoho tsa sebopeho le tšebetso ho serotoninergic DRN neurons (Veerakumar et al., ) mme e felisitsoe ka botlalo ho latela ho putlama ha serotoninergic ho la DRN (Hamani et al., ). Ho liphoofolo tsa naïve, ts'ebetso ea ts'ebetso ea optogenetic ea mPFC-DRN e ipiletsang ka ho bonesa ha li-terminals tsa mPFC ho DRN e khothalelitse ts'ebetso ea ts'ebetso ho FST (Warden et al., ). Ho fapana le moo, khanya ea sethepu sa mPFC ho LHb e kentse ts'ebetso ho FST, athe leseli la vmPFC pyramidal cell e ne e se letho. Haufinyane tjena, menyetla ea vmPFC-DRN tseleng e tepelletsang joaloka naha e sithabetseng e ile ea hlahlojoa ho sebelisoa paradigm e sa feleng ea Chiminis et al., ). Liphoofolong tsa naïve, ts'ebetso e pheta-phetoang ea ChR2-Mediated ea vmPFC-DRN e eketsehile ho qoba sepheo sa sechaba, e bonts'a mofuta oa phenotype o nyahamisang. Tumellanong le sena, Arch-mediated photoinhibition ea tsela e ts'oanang e ile ea thibela nts'etsopele ea ho tlosa setjhaba ho liphoofolo tse tlisoang ke ho hloloa hoa sechaba (Challis et al., ). Bangoli ba fana ka bopaki ba hore li-neuron tsa vmPFC li hlile li lebisa li-neurons tsa GABAergic ho DRN, tse ka 'nang tsa thibela li-neurot tsa serotonergic, tse hlalosang litlamorao tse bohloko tse ba boneng. Leha ho le joalo, datha ea bona ha e lumellane le litlamorao tse khahlanong le khatello ea maikutlo, tse fumanoang ho FST kamora ho hlohlelletsa tsela ea vmPFC-DRN (Warden et al., ). Sena se fana ka maikutlo a hore tsela ea mPFC-DRN e ka ameha ka mokhoa o fapaneng ho laola tšebelisano ea sechaba le boits'oaro bo bobe, boits'oaro bo habeli bo hlahisa liteko tsena tsa liteko. Ntle le moo, litlhaloso tse fapaneng li ka hlalosoa ka phello e fapaneng ea phello e mpe (Warden et al., ) vs. pheta-phetisetso ea katloso ea morao-rao ea tsela ea vmPFC-DRN (Challis et al., ) ponong ea boitšoaro bo sithabetsang maikutlo. Le ha ho le joalo, liteko tsena li bonts'a liphallelo tsa MPFC ho bokhoni ba ho ikamahanya tlasa maemo a phephetso (proactive vs. passive reacaction) kapa maikutlo (a nkang liqeto tse nkang liqeto) maemo a phephetsang, a sitisoang haholo ke khatello ea maikutlo (Gotlib et al., ; Derntl et al., ; Volman et al., ; Cruwys et al., ). Vialou et al. () e bonts'itse hore ts'ebetso ea PLC-NAc le PLC-BLA li kenella ka mokhoa o fapaneng phapang ea khatello ea maikutlo le boits'oaro bo amanang le ho tšoenyeha. Ba fumane hore khatello ea maikutlo e sa feleng ea khatello ea maikutlo ea defeatFosB ho PLC, e neng e hokahanngoa le polelo ea "cholecystokinin B" (CCKB) le kenyelletso ea khatello ea maikutlo e teng liphoofolong tse fuoang khatello ea khatello ea mantlha (Vialou et al. , ). Ho ts'ehetsa sena, ts'ebeliso ea lehae ea ngaka ea CCK agonist (CCK-8) ho PLC e khothalelitse tšusumetso ea phenotype le ChR2-mediated optical stimulation of PLC glutamatergic terminals in the NAc thibela CCK-8 infititility defendedits of social (Vialou et al. , ). Ho kenella ha CCK-8 ho PLC le hona ho hlahisitse phello ea ho tšoenyeha ho EPM mme phello ena e khutlisitsoe ke ho nka lifoto tsa PLC-BLA, empa eseng PLC-NAc, tsela. Ha re li nka hammoho, lintlha tsena li bonts'a bohlokoa ba ho khetha merero ea mPFC ka boomo ho khetholla karolo ea bona taolong e tlase ea taolo ea likarolo tse tlase maemong a sithabetsang le (mal) ho arabela ka mokhoa o ikhethileng ho khatello ea maikutlo (Lobo et al., ; Yizhar, ; Shenhav le Botvinick, ).

Ntle le phetisetso ea likhakanyo tsa tšebetso, optogenetics e boetse e sebelisitsoe ho kena lipakeng le mPFC e amanang le litaba tsa DA (Chaudhury et al., ; Friedman et al., ; Gunaydin et al., ). Ho khetha ka boomo moqomo oa VTA-mPFC DA, Chaudhury et al. () li-microinjected a khutlisetsa marangrang a pseudorabies a fetisang vaerase bakeng sa Cre mPFC le ChR2 e thehiloeng ho CR kapa NpHR ho VTA. Photoinhibition ea tsela ea VTA-mPFC tseleng e fokotsitse tšebelisano ea litheko ho litoeba tse neng li etelletse tlasa taolo ea maemo a tlase sechabeng (Chaudhury et al., ). Ho khahlisang, ba fumane hape hore sekhahla sa ho thunya ha li-neurons tsa VTA DA setsing seo ho mPFC se fokotsehile haholo ho litoeba tse senyehileng tse ileng tsa ba le khatello ea khatello ea sechaba. Ha re le hammoho, sena se bontša hore ho lokolloa ha DA ho mPFC ho ka thibela nts'etsopele ea khatello ea maikutlo e ka etsahalang. Channelrhodopsin-2-Mediation activation ea VTA-mPFC tsela ha e-ea ka ea ama nts'etsopele ea ts'ebetso ea phenotype e latelang ho ts'oaroa ha tlhabollo ea maemo a tlase sechabeng (Chaudhury et al., ). Leha ho le joalo, ho ts'oaroa khafetsa ha ChR2-e hlalosang VTA-mPFC neurons ho khutlisitse tšireletso ea sechaba ho sechaba se nang le khatello ea maikutlo se latelang ho hloloa ho sa feleng sechabeng (Friedman et al., ). Litlamorao tse hanyetsanang li se li bonoa ke chR2-mediated stimulation of the VTA-mPFC DA way in naïve mice, e sa bonts'eng phetoho litšebelisanong tsa sechaba, empa ho fapana le moo e bonts'itse keketseho ea boits'oaro bo ts'oanang le ho tšoenyeha le boits'oaro ba sebaka (Gunaydin et al., ). Ka bobeli, lithuto tsena li bonts'a hore tataiso ea litlamorao tsa boits'oaro e latela boemo ba phoofolo. Liphoofolong tse nang le khatello ea maikutlo, liphetoho lipuisanong tsa mPFC tse amanang le DA li lekane ho matlafatsa ts'oaetso ea ho ba le ts'oaetso kapa ho khutlisa boitšoaro bo sithabetsang.

Taolo ea optogenetic ea mPFC le libaka tsa boko tse hokahaneng e tsoetse pele haholo kutlwisiso ea rona mabapi le ts'ebetso ea methapo ea khatello ea maikutlo (Lammel et al., ). Haholo-holo mehato ea bohlokoa e se e entsoe ho arola monehelo oa merero e hlakileng ea mPFC lits'ebetsong tse ikhethang tsa boits'oaro bo nyahamisang, joalo ka boits'oaro ba sechaba, matšoenyeho le boits'oaro bo amanang le moputso. Ho khahlisang, lithuto tsena li boetse li senotse mekhoa ea ho iphelisa, ho kenyeletsa anatomical (VTA-mPFC DA projection) le litselana tsa methapo (CCK), tse ka bonts'ang ts'ebeliso e ntle ho loants'a bothata bona bo fokolisang. Nakong e tlang, profiling ea liphatsa tsa lefutso le liprotheine tse hlahisitsoeng ho mPFC holim a ts'usumetso ea optogenetic e ka fana ka temohisiso mokhoeng oa limolek'hule tse etsang hore ho be bonolo ho sebetsana le maemo a sithabetsang mme e ka bula menyetla e mecha ea ho kena lipakeng tsa bongaka (Lobo et al., ).

Leha ho bile le tsoelo-pele ena e entsoeng ka lisebelisoa tsa optogenetic, litaba tse 'maloa tse amanang le tleliniki ha li e-so rarolloe. Ha maikutlo a sithabetsang a tšoauoa ke polelo ea motho ka boeena ea phenotypic, a nang le matšoao a fapaneng, tlhahlobo e le 'ngoe ea boits'oaro bo nyahamisang le ho tšoenyeha a sebelisa mekhoa e bonolo ea boits'oaro (FST, EPM, precrose prefer) e ka fokotsa boleng ba phetolelo ea liphetho tsena (Belzung et al., ), ho pheha khang bakeng sa nts'etsopele le ts'ebeliso ea mehlala e nang le bonnete bo ntlafalitsoeng ba ho ithuta boemo bo sithabetsang. Taba ea bohlokoa ke hore manonyeletso a amang ts'ebelisano pakeng tsa liphoofolo le liphoofolo ha a hlile a bonts'a mofuta o nyahamisang, empa e ka ba sesupo sa mekhoa e tšehetsang boitšoaro ba sechaba ka kakaretso. Kahoo, li-circuits tsa MPFC tse khethiloeng li kanna tsa ba le karolo maemong a mang a kelello a bonts'ang liphoso tsa maemo a bophelo, mohlala, likotsi tsa autism, mathata a ho tšoenyeha le lefu la kelello (sheba ka tlase; Yizhar, ; Allsop et al., ). Ntle le moo, ho latela ts'ebetso ea ho bala (mohlala, socialility kapa anhedonia), ho kenella ha optogenetic ho ka ba le phello e khethollang (Albert, ), ho hatella ho eketsehileng karolo ea karolo ea likarolo tse ikhethang tsa potoloho maemong a rarahaneng a boits'oaro. Qetellong, tšebeliso ea lipotoloho tse potolohang khatello ea maikutlo tse bakang khatello ea maikutlo, e leng sesosa se kotsing ea ho tiisetsa bothata bona, e lutse e le sebaka se sa nkoang mabapi le ho qhekella ha optogenetic, empa e na le ts'episo e kholo ea ho hlakisa merero ea nova e ka sebelisetsoang kalafo. ea lefu lena le atileng la mafu a kelello.

Schizophrenia

Schizophrenia e tšoauoa ka kelello e holisang haholo (ho hopola, ho hlokomela), ho khothaletsa matšoao a ho se sebetse hantle le ho se sebetse hantle (ho ama hampe, ho anhedonia), hammoho le puo e sa hlophiseheng le boits'oaro bo bobe ba koloi (American Psychiatric Association, ). Pharmacotherapy ea morao-rao e shebana le matšoao a fokolang feela, ha boholo ba liphekolo li sa lekanngoe ho laola bofokoli bo amanang le psychosis mme ba sa khone ho hlokomela sesosa sa mantlha sa bokooa, ke hore, ho fokotseha hoa kelello (Ross et al., ; Cho and Sohal, ). Ha pathogenesis ea schizophrenia e ntse e sa hlaka ebile e ka 'na ea kenyelletsa potoloho e rarahaneng ea neural, li-optogenetic disgment tsa methapo e ka tlase ea neural le neuroadaptations li tla re thusa ho utloisisa bothata bona ba kelello bo seng bo sa phekolehe (Peled, ; Cho and Sohal, ).

Boholo ba bofokoli ba kelello bo tsamaisanang le schizophrenia, bo kang ts'ebetso e sa sebetseng hantle le mohopolo oa episodic le taolo e senyehileng ea motlakase, bo lekantsoe mosebetsing oa PFC o sa sebetseng, bo fella ka khokahano e fetotsoeng le libaka tse ka tlasa sebaka, joalo ka amygdala, striatum le hippocampus ( Ross et al., ; Meyer-Lindenberg, ; Arnsten et al., ). Ho na le likhopolo tse ngata mabapi le phetoho ea mPFC e bakang matšoao a ho fetoha ha maikutlo, ho kenyelletsa molumo o fetotsoeng oa dopaminergic, phetoho molemong oa tekano ea E / I le ts'ebetso e sa tloaelehang lethathamong la lipapali tsa gamma (Meyer-Lindenberg, ; Lisman, ). Mekhoa ea Optogenetic e se e qalile ho sebetsana le melemo ea likhopolo tsena ka ho fana ka leseli la ho qhekella ka mekhoa e ka tlase ea matšoao a heterogenible a schizophrenia, haholo ts'ebetso ea tlhaiso-leseling le tlatsetso ea tlhahisoleseling e amanang le bothata bona (Wang le Carlén, ; Touriño et al., ).

Karolo e kopanetsoeng ea dopamine e filoe hypothesized ho kenya letsoho kholisong ea lefu la kelello. Haholo-holo, ho nahanoa hore phetisetso e eketsehang ea DA tsamaisong ea mesolimbic le tšebetso e tšoanang ea DA akhaonteng ea mPFC bakeng sa tlhahiso ea matšoao a schizophrenic (Brisch et al., ; Cho and Sohal, ). Ntle le moo, ts'ebetso e sa lekanyetsoang ea li-cortical D1-Rs le D2-Rs, tse nang le litlamorao tse hanyetsanang tsa thabo ea neuronal (Beaulieu le Gainetdinov, ), e nkuoa e le ea bohlokoa bakeng sa ts'ebetso ea litaba e senyehileng le ponahatso ea matšoao a matle le a mabe ho schizophrenia (Seamans le Yang, ; Durstewitz le Seamans, ; Brisch et al., ). Ho kenya letsoho ha D2-R ho ts'ehetsoa ke taba ea hore li-antipsychotic tsohle tse ntseng li sebelisoa ho phekola matšoao a nepahetseng a schizophrenia, thibela mosebetsi oa D2-R (Cho le Sohal, ). Ntle le moo, li-D2-R tsa pele li na le karolo e tebileng lits'ebetsong tsa kelello tse sitisoang ke lefu la kelello, ho kenyelletsa le mohopolo oa ho sebetsa le ho kenella ha sensorimotor, joalo ka ha ho reriloe ke litheko tsa phetoho e kholo le tlhabollo ea meriana (Ralph et al., ; Seamans le Yang, ; Durstewitz le Seamans, ). Optogenetic modulation ea D2-R e hlahisang li-neurons ka har'a mPFC e fane ka leseli le lecha ts'ebetsong ea D2-Rs le tlatsetso ea bona ho matšoao a schizophrenia. Ts'usumetso ea Intra-mPFC ea moqapi oa ChR2 ea itšetlehileng ka C2-R :: creice e ile ea etsa hore polelo ea ChR2 e hlahisoe ke lisele tsa "pyramidal" tse kenang thalmus (Gee et al., ). Lirekoto tsa litheko tsa boiketsetso li bonts'itse hore, motheong oa pele, quinpirole ea D2-R e bile le phello e fokolang ho liente tsa hona joale ho li-neuron tsa D2-R, leha ho le joalo, ts'oarelo e kholo ea kamora ho putlama e etsahetse ha ts'ebetso ea quinpirole e etelletsoe pele ke ts'ebetso ea optogenetic ea konteraka ea D2-R- ho hlahisa li-neurons tsa projeke ea mPFC, ho baka ho fokotseha hoa matla le ho phahloha ha li-millisecond tse makholo (Gee et al., ). Kaha ho na le ho qaqisoa ha polelo ea D2-R ho cortico-thalamic projeke ea ho haha ​​V neurons, D2-R-Mediated after-depolarization e kanna ea ntlafatsa tlhahiso ho meaho e ka tlase. Tlas'a maemo a bophelo, joalo ka tlhahiso e fetisitsoeng ea D2-R e bonoang ho schizophrenia (Seman le Kapur, ), tlhahiso ena e ntlafalitsoeng ea matšoao e ka ntlafatsa boemo ba lerata ho mPFC, ka hona, e fetohela tlhahiso-leseling ea tlhahisoleseling libakeng tse subcortical le ka ho ntlafatsa ts'ebetso ea psychosis. Ha boemo ba lerata ka har'a mPFC bo nahanoa hore bo eketseha ho bakuli ba schizophrenic (bo tšohliloeng ka tlase), ho fokotsa D2-R-Mediated after-depolarization e ka ba motheo oa neurophysiological bakeng sa phello e molemo ea li-antipsychotic ho matšoao a schizophrenia. Patlisiso e ngoe hape u sebelisa Ka vivo mefuta e tla tlameha ho netefatsa hore na D2-R e kentsoe kamora ho depolarization e kentse letsoho ts'ebetsong ea kelello e hlokometsoeng ho schizophrenia.

Khopolo-taba ea tekano ea E / I e fana ka maikutlo a hore ho phahama ka tekanyo ea cortical E / I, e kopantsoeng ka methapo ea methapo ea methapo kapa phokotseho ea maqhubu a thibelo ea kutlo, e theolang matšoao a boits'oaro le a kelello a lefu la kelello. ; Wang le Carlén, ). Marang-rang le litlamorao tsa boitšoaro bo fetotsoeng ba E / I e fetotsoeng ho MPFC e rarollotsoe ka ts'ebetso e tsitsitseng ea ts'ebetso opsin (SSFO), phetoho ea ChR2 ka nako e fokotsitsoeng haholo ea deactivation (~ 30 min) (Yizhar et al., ; Yizhar, ) holim'a ho chechisoa ke khanya e le 'ngoe ea leseli le leputsoa, ​​ka tsela eo, fokotsa mokhoako oa ho thunya ho ka bang teng ka methapo ea kutlo ea SSFO. Ho nka lifoto ka bokhutšoanyane ha li-neuron tsa "NFPO" tse hlalosang mantsoe ka piramite ho ile ha eketsa tekano ea E / I, ts'ebetso ea ts'ebetso ea tlhahisoleseling sethaleng sa cellular le ts'ebetso e phahameng ea maqhubu a sephiri, e ts'oanang le lipontšo tsa tliliniki ea schizophrenia (Yizhar et al., ) (bona karolo e ka tlase). Boemong ba boitšoaro, manong ana a ne a lekane ho felisa tšebelisano 'moho le ho sitoa ho fumana mohopolo ka tšabo. Ts'ebetso e ntlafalitsoeng ea E / I ka kotloloho ea pono ea mantlha ha e fetole boitšoaro ba batho, bo amanang le ho hlaka ha mPFC ho loants'eng mefokolo ena ea boits'oaro. Ho khahlisang, ho nyenyefatsoa ha li-neurons tsa SSFO tse hlalosang mPFC GABAergic PV ha hoa ka ha ama tšebelisano ea sechaba le maemo a tšabo (Yizhar et al., ), leha e le hore e fokotse haholo ts'ebetso ea spiking le synaptic. Leha ho le joalo, liphoso tsa boiketlo ba sechaba tse hlokometsoeng kamora ho kenella ha lifaele tsa lisele tse hlalosang mantsoe tsa SSFO li ile tsa pholosoa ka karolo e itseng ke ts'ebetso ea ts'ebelisano ea li-neuron tsa ChR2 tse hlalosang PV (Yizhar et al., ). Joalokaha ho hlalositsoe pejana, thibelo ea li-neurons tsa MPFC PV e ka baka khaello e matla ea ho hopola mesebetsi (Rossi et al., ), hape e hatisa bohlokoa ba molumo o monate oa tlhompho ea cortical. Haholo, tekano e phahameng ea E / I kahare ho mPFC e boetse e nahanoa hore e kenya letsoho ho dysfunction ea sechaba e amanang le mathata a autism spectrum (Yizhar et al., ), ka hona, liphumano tsena li ka supa mochine oa pathophysiological o sebetsanang le mathata a akaretsang a boitšoaro ba sechaba. Leha ts'ebeliso ea li-aids tsa SSFOs ho hlalosa litholoana tsa bosholu ba mPFC E / I maemong a seloko le ts'ebelisanong ea sechaba, ho fetoloa hoa tekano ea E / I ho schizophrenia le autism ho bakoa ke ts'ebetso ea methapo ea methapo ea methapo. Ka hona, ho bakuli, tekano ea E / I e phahamisoa bakeng sa nako e fetang hole nako ea nako ea deactivation ea li-SSFO tse fumanehang hona joale. Litlamorao tse "mpe haholo" tsa phetoho ho tekano ea E / I ho liphoofolo tse tloaelehileng tsa tlholeho li lokela ho hlalosoa ka hloko. Seo ho buuoang ka sona, mananeo a optogenetic a sebelisang li-SSFO ka lekhetlo la pele a bonts'itse karohano e matla ea phapang ea phetoho ho mPFC E / I ho leka-lekana ts'ebetsong ea netweke le boits'oaro. Ntle le moo, li-SSFO li ka sebelisoa ho lekola hore na E / I e lekantsoe ke mafu a mang a mafu a kelello, ho kenyelletsa autism, khatello ea maikutlo le tšenyo, mohlomong ho kopanya etiology ea mathata ana (Tye le Deisseroth, ).

Tsela ea boraro e ikemiselitseng ho hlalosa bofokoli ba kelello ba bakuli ba schizophrenia e kenyelletsa sebopeho sa gamma, 30-80 Hz neuronal oscillations tse etsang mosebetsi oa bohlokoa ho hokahanyang tšebetso ea methapo kahare le pakeng tsa libaka, tse tsebahalang hore li hlokahala bakeng sa ho hopola, ho lemoha le ho ela hloko. (Lewis et al., ; Wang le Carlén, ), hape e bohlokoa mesebetsing e meng e mengata ea boko. Ho bakuli ba schizophrenia, litlolo tse sa tloaelehang tsa gamma li 'nile tsa bonoa khafetsa,' me li lumellana le liphetoho phepong ea mohopolo le taolo ea kelello (Uhlhaas et al., ; Uhlhaas & Singer, ). Ha ts'ebetso ea neuron ea PV e sa sebetse hantle, ts'ebetso ea subhibtimal inhibitory e lebisa ho desynchronization, e kenya letsoho morerong oa gamma o fetotsoeng mme ka mokhoa o loketseng ho sebetsa ho senyeha ha memori ho amanang le schizophrenia (Lewis et al., ). Tumellanong le maikutlo ana, motsoako oa GABA le phumano ea lehae li fokotsoa ka mokhoa o tsitsitseng ho PFC ea bakuli ba schizophrenia mme phetoho ena e kopantsoe ka ho khetheha ke li-neurons tsa PV, e bolelang ts'ebetso e fetelletseng ea palo ena ea maqhubu a mahareng (Lewis et al., ). Ka mokhoa o ts'oanang, ho fokotsoe ha ts'ebetso ea PV ho PFC ea bakuli ba schizophrenic ho tlalehiloe (Beasley le Reynolds, ). Lithuto tsa optogenetic li netefalitse bohlokoa bo bohlokoa ba li-interneurons tsa Port ea Cortical ho khanna li-oscillations tsa gamma (Cardin et al., ; Sohal et al., ). Sohal et al. () e bonts'itse hore ho nka lifoto tsa ChR2-lisele tse buoang tsa PFC pyramidal elicited gamma oscillations Ka vivoleha ho le joalo, NPHR-Mediated inhibition ea PV + e kenelletseng ka nako e le 'ngoe e hatelletse matla a gamma, e fana ka tlhahiso ea hore lisele tsa pyramidal li qalelle ts'ebetso ea methapo ea methapo ea PV. Habohlokoa, ha ho beha li-neuron tsa "pyramidal" ho kenella khafetsa sebopeho sa "gamma-frequency, phetiso ea" miccircuit "e ile ea ntlafatsoa ka ho fokotsa lerata la potoloho le ho holisa matšoao a potoloho, ho kenyelletsa le lipontšo ho li-interneurons tsa lehae (Sohal et al. ). Parvalbumin interneuron e tsamaisoa ke li-gamma-mediated neuronal synchrony tse itšetlehileng ka ts'ebetso ea li-receptor tsa NMDA, joalo ka ha ho etselitsoe ho hlakoa ha NMDA receptor ho PV neurons ho sitisoa ha indogenetic ea ts'ebetso ea li-oscillations tsa gamma mme ho felletse ka ho fokotseha hoa khethollo ea kelello, e tšoanang le bofokoli ba schizophrenic (Carlén et al. ). Hammoho, modumo ea optogenetic e khethiloeng ea tšebetso ea maqhubu a PV e netefalitse hore ts'ebetso ena ea neuronal subtype e tsamaisa oscillations ea gamma, eo ka tatellano e khothalletsang ts'ebetso ea tlhahisoleseling e potlakileng le e lebisitsoeng; “ho chorisa” ha karabelo ea maikutlo ho liphihlelo tsa sensory (Wang le Carlén, ). Liphetoho likhethong tsa motsoako oa kelello le tsona ho nahanoa hore li tlasa maemo a mang a kelello, ho kenyeletsa ho ferekana ha kelello le ho ruruha ha mmele, le lefu la ho akheha (Uhlhaas le Singer, ; Sheline et al., ). Kahoo, boiteko bo reretsoeng ho hlakisa haholoanyane liphetoho tsa potoloho le tsa limolek'hule tse tlatsetsang molatong o fetisisang oa li-oscillation tsa neuronal li bohlokoa haholo.

Ha ho kopantsoe hammoho, manolo a pele a lipono tsa lipampiri tsa mPFC a netefalitse bonyane likhopolo tse seng li ntse li le teng tse ikemiselitseng ho hlalosa lits'ebetso tsa neuropathological tse tlasa schizophrenia. Ts'ebetso e ntlafalitsoeng ea thabo, mohlomong ka lebaka la ho hlaseloa ha D2-R, e hlahisang phetisetso ea tlhahiso ea methapo ea methapo le ho senyeha ha tlhahisoleseling ea cortical e tlatsetsa matšoao a amanang le bothata bona. Ha ho fanoa ka mofuta oa "schizophrenia" o rarahaneng le o rarahaneng, ho ka ba thata ho etsisa sebopeho se felletseng sa phoofolo ea mofuta oa liphoofolo. Leha mananeo a optogenetic bokong ba methapo a bohlokoa haholo bakeng sa ho fana ka tataiso e ncha lefapheng lena la lipatlisiso, boleng ba phetolelo ea mekhoa e hlokometsoeng e ntse e le phephetso e hlokang ho rarolloa nakong e tlang.

lemalla ntho e

Batho ba lemaletseng ts'ebeliso ea lithethefatsi ba bontša boitšoaro bo botle bo sa thibeloang ho pheta-pheta ho batla lithethefatsi, ho e sebelisa le ho hlaphoheloa ts'ebelisong ea lithethefatsi leha ho le joalo hangata ho bile le litlamorao tse mpe (Hyman, ). Tšebeliso ea lithethefatsi ke qetello ea letoto la liphetoho tse tsoang ho tšebeliso ea lithethefatsi ea hedonic ho ea tloaelo le ho qobelloang, e tsamaellanang le liphetoho tsa nako e telele lijaneng tsa neural (Robinson le Berridge, ; Kalivas le Volkow, ). Litefiso tse phahameng tsa ho oela hape ke bothata bo boholo kalafong ea bokhoba, kaha batho ba lemaletseng ts'ebeliso ea lithethefatsi ba lula ba le kotsing ea ho khutla le kamora nako e telele (likhoeli le lilemo) ea ho khaotsa (Kalivas le O'Brien, ). Tlokotsi ena e phehellang e nahanoa hore e bolokiloe ke mehopolo e kopaneng le e phehellang ea likamano tsa litla-morao tsa lithethefatsi le litloaelo tsa tikoloho (Hyman et al., ). Ho potoloha ha boko ho tšehetsang bokhoba ba tahi ho rarahane ho rarahane, empa bopaki bo bongata bo bonts'a hore mPFC e na le karolo ea bohlokoa tlatsong le pheellong ea boits'oaro bo bobebe (Kalivas, ). Haholo-holo, mPFC e kentsoe tlhokomelong ea ts'ebetso ea ts'usumetso e ntle ea ho khothaletsa ts'ebeliso e mpe ea lithethefatsi, polelo ea mehopolo e amanang le lithethefatsi le ho khutlela morao ho ho batla lithethefatsi (Van den Oever et al., ; Hogarth et al., ; Peters et al., ). Mekhoa ea Optogenetic e netefalitse ts'ebetso ea bohlokoa ea mPFC mehlaleng ea liphoofolo le ho fana ka leseli le lecha ka monehelo oa nakoana oa litlatsetso tsa mPFC le merero ho NAc ho qobella ho nka lithethefatsi le boits'oaro ba ho batla lithethefatsi.

Bopaki bo tsoang liphuputsong tse entsoeng ka neuroimaging bo bontša hore hypofunction ea mPFC e baka tahlehelo ea taolo ea ho fokotsa ts'ebeliso ea lithethefatsi tsa batho (Goldstein le Volkow, ). Khopolo ena ea morao-rao e sa tsoa sebetsoa ka ho sebelisa optogenetics litekong tse ntseng li tsoela pele ho iphekola ka koae leha e le moputso oa koae ka ho khothaletsoa ho matlafatsang. Chen et al. () e bonts'itse hore nako e telele ea ho itlhompha ka koae e fokotsa ts'ebetso ea neuron ea PLC, mme e bile le phello e matla ho litheko tse hananang le boikhohomoso. Ho khutlisetsa ts'ebetso ea piramite ea PLC ka ts'usumetso ea optogenetic ho fokotsa ho kenella ha k'hok'heine ha e le khahlanong le likhoto (Setšoantšo se bontšang (Figure2A) .2A). Ho fapana le moo, ha li-neuron tsa PLC li ne li khutsisoa ka mokhoa o khahlisang, likhoto tse sa hanyetsaneng li ile tsa ikoetlisa ka mokhoa oa ho iphekola ka koae ka ho sisinyeha ha leoto. Boithuto bona bo bontša hore ha tšebeliso ea koae e entsoe ka litlamorao tse mpe, hypoactivity ea lisele tsa phiramide ea PLC e thusa ho lahleheloa ke taolo ea thibelo ea tšebeliso ea khatello ea koae.

Setšoantšo sa 2  

Bopaki ba optogenetic bakeng sa ho kenya letsoho ha mPFC ho boits'oaro bo eketsang. Flash e putsoa: photoinhibition; boputsoa bo buluu: khanya ea khanya. ↑ = Ho nka litlhare / ho batla litlolo tse ntlafalitsoeng; ↓ = Ho fokotsa / ho batla lithethefatsi. Manolo a optogenetic a bontša ...

Ho kenella hoa meriana litabeng tsa liphoofolo tsa batho ba batlang lithethefatsi tse nang le maemo a bonts'a hore dmPFC le vmPFC li kenya letsoho pontšong ea boitšoaro bona bo ikhethileng (Peters et al., ; Van den Oever et al., ). Le ha ts'ebetso ea dmPFC e nahanoa e khanna likarabo tse batlang lithethefatsi, vmPFC e nts'etsapele kapa e thibela likarabo tse batlang lithethefatsi ho latela mofuta oa lithethefatsi tse pele tse neng li sebelisoa le ts'ebetsong ea linako tsa ho timela pele ho paki e batlang lithethefatsi.t (McLaughlin le Bona, ; Peters et al., ; Roger et al., ; Koya et al., ; Lisa Smith ; Lubber et al., ). Ebile, lintlha tse 'maloa tsa bopaki li fana ka maikutlo a hore ILC e buella ho kopanya le ho hlahisa mohopolo oa ho timela (Petros et al., ; LaLumiere et al., ), ka lebaka leo, thibelo ea sebaka sena kamora ho ithuta ho timelitsoeng ho etsa hore motho a arabe karabo ea pele ea koae. Phokotso ea optogenetic ea vmPFC e atolositse lipatlisiso tsena ka ho bonts'a lisele tsa vmPFC pyramidal ehlile li kenya letsoho ho hlahiseng le ho felisoa hoa maemo a batlang koae ea cocaine, empa ka nako e its'epahalletseng (Van den Oever et al., ;; Setšoantšo Figure2B) .2B). Channelrhodopsin-2-mediation activation of vmPFC cell pyramidal cell activates extination of cocaine conditioned place preference (CPP) memory fela fa photostimulation e ne e tsentswe dibeke tsa 3 morago ga moo, mme e seng letsatsi la 1 morago ga seemo. Tumellanong le tlhokomeliso ena, NpHR-Mediated inhibition ea li-neuron tsena e thibetse ho fela ha memori ea CPP 3 libeke kamora ho ba maemong. Ho makatsang ke hore, Photoinhibition e ikhethile ka mokhoa o ikhethileng oa memori ea cocaine ea letsatsi la 1. Ka kopanelo, manolo a optogenetic a lisele tsa phiramide a supa tokisetsong ea nakoana ea potoloho e laolang polelo ea mehopolo e amanang le koae le karolo e arohaneng ea vmPFC taolong ea cocaine e nang le maemo e batlang e sa sebetse nako.

Boithuto ba optogenetic bo netefalitse hore ts'ebetso ea PLC ea hlokahala bakeng sa ho khutlisetsa mokhoa o batlang oa koae ho liphoofolo tse tima. Hoa tšoana le ho qaptjoa ha meriana, ts'ebetso ea li-neuron tsa PLC (e sebelisang morekisi ea sa khethang) e fokotsitseng ho khutlisetsoa hoa k'hok'heine ea cocaine (Stefanik et al., ). Ntle le moo, sehlopha se tšoanang se bonts'itse hore tsela ea BLA-PLC e kenella ka matla ho khutlisetsoeng hoa koae ka ho ts'oaroa ha lithibelo tsa ponts'o ea BLA ho PLC (Stefanik le Kalivas, ). Thibelo ea Optogenetic ea dmPFC pyramidal neurons e boetse e khantšelitse khatello ea maikutlo e bakiloeng ke lijo tse fumanehang habonolo tse batloang ke likhoto (Calu et al., ), e fana ka tlhahiso ea hore mekhoa e fapaneng e qobelle potoloho ea dmPFC ho etsa hore mosebetsi oa ho fumana moputso o khutlisetsoe hape. Ntle le moo, sena se bontša hore ts'ebetso ea PLC e khanna ho khutlisetsoa hoa koae le ho batla moputso oa tlhaho, athe ts'ebetso e eketsehileng ea li-neuron tse ts'oanang e hatella cocaine e qobelloang (Chen et al., ). Ts'ebetso e hanyetsanang ea PLC e ka itšetleha ka ho ba teng kapa ho se be teng ha koae litekong tse sebetsang. Sena se ts'ehetsoa ke ho bona hore Photoinhibition ea lisele tsa phiramide ea PLC e ntlafalitse ts'ebetso ea boikoetliso 'me ea boela ea khutlisetsoa ha ho ts'oaroa koae ka likhoto tse fuoeng kemiso e phahameng ea tšebeliso ea koae (Martín-García et al., ). Li-interneurons tsa GABAergic ha li so ka tsa fetoloa le mefuteng ea bokhoba ba ho lemalla, empa karolo ea lipuisano tsa PV thutong le ho feliseng ha tlhaho e sa tsoa hlahlojoa. Channelrhodopsin-2-Mediation activation ea li-interneurons tsa PLC PV ha e a ka ea ama ho nkuoa ha tsamaiso ea boithatelo ba moputso, empa e potlakisitse ho felisoa ha moputso o batlang ka ho thibela ts'ebetso ea netweke ea PL (Sparta et al., ). Hore na ts'ebetso ea PLC PV e boetse e ama ho felisoa hoa ho batla lithethefatsi e lula e le sehlooho sa lipatlisiso tsa nako e tlang.

Ka ho kopanya tlatsetso ho tsoa mehloling e joalo ka BLA, VTA le HPC le ho fetisa tlhahiso e thabisang ho NAc, mPFC e nahanoa hore e fana ka taolo holim'a potoloho ea makoloi ho laola ho araba lithethefatsi le ts'usumetso e amanang le lithethefatsi. (Kalivas et al., ). Libaka tsa Dorsal tsa MPFC li rera haholo ho dorsolateral striatum le NAc konokono, athe libaka tse kenang ka hare ho naha li shebile haholo dorsomedial striatum le NAc khetla (Voorn et al., ). Pliteko tsa tlhahlobo e kotsi li hlile li ts'oarelletsa tsela ea mantlha ea dmPFC-NAc le tsela ea khetla ea vmPFC-NAc tseleng ea lithethefatsi le cueine e kentsoeng cocaine le heroin. (McFarland et al., ; LaLumiere le Kalivas, ; Peters et al., ; Bossert et al., ), empa ka mokhoa ona litlamorao tse tseleng tse sa tobang li ke ke tsa hlakoloa. Photoinhibiton ea liteishene tsa preCaptic tsa PLC ka hara NAc konokono e kentsoe k'hok'heine ea mofuta oa cocaine e ntlafalitsoeng (e leng Stefanik et al., ), ho netefatsa hore projeke ea monosynaptic glutamatergic e tsoang ho PLC ho isa ho NAc ea mantlha e na le karolo e tebileng karabong ena ea boitšoaro. Bopaki ba optogenetic bakeng sa ho kenya letsoho ha tsela ea khetla ea mPFC-NAc e fanoe ke phetoho ea optic ea li-terminals tsa ILC lipapatsong tsa kelello tsa NAc tse fumanoeng ho liphoofolo tse ileng tsa pepesetsoa koae (Suska et al., ). Sena se senotse hore tlhahiso ea presynaptic ea liteishene tsa MPFC khetla ea NAc e matlafalitsoe kamora hore matsatsi a mabeli a (a 1) le ho pepesetsoa nako e telele (matsatsi a 45) ho pepesehela koae, empa e le kamora ho pepesoa khang ena. ka mor'a nako e itseng. Matlafatso ea presynaptic e bakiloe ke keketseho ea menyetla ea tokollo ea glutamate, ho fapana le ho eketseha ha boholo ba tlhahiso ea glutamatergic kapa palo ea libaka tse sebetsang tsa tokollo (Suska et al., ). Ho khahlisang, ho pepesetsoa ha koae ha hoa ka ha ama phetisetso ea presynaptic ho projekeng ea khetla ea BLA-NAc (Suska et al., ), ho fana ka tlhahiso ea hore tlhahiso ho tsoa ho mPFC e ratoa haholo ke ho kenya letsoho ha BLA kamora tsamaiso ea koae. Phuputsong e ntle ke Ma et al. () e bonts'itsoe hore boikoetliso ba koae bo kentse ts'ubuhlellano e khutsitseng tseleng ea mPFC-NAc. Ho khahlisang, li-synapses tse khutsitseng tseleng ea khetla ea ILC-NAc e holofalitsoe ke ho hira GluA2-e se nang li-AMPA-Rs (e bonoang ka letsatsi 45 ea ho ila), athe li-synapses tse khutsitseng tseleng ea PLC-NAc ea mantlha e hira GluA2-e nang le AMPA-Rs. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors e haelloang ke setsi sa GluA2 li-calcium permeable, li na le ts'ebetso e kholo ea ts'ebetso ea kemiso, li bonts'a ts'ebetso ea kapele ea ts'ebetso ea liea-kemiso mme ka tsela eo e kenya letsoho ho potlakisa ho saena ha li-typaptic, homeostatic synapticaling e khutsoanyane le nako e telele ea polasetiki (bakeng sa tlhahlobo e ntle haholo bona Isaac et al., ). Optogenetically e bakile khatello ea maikutlo ea nako e telele (1 Hz bakeng sa 10 min) e hlahisitse li-synapses tse khutsitseng litseleng ka bobeli, empa sena se ka ntlafatsoa (khetla ea ILC-NAc) kapa sa fokotsoa (motheo oa PLC-NAc) se latelang sa koae se batlang ho sebelisa koae (Ma et al., ), e tšehetsa likarolo tsa dmPFC le vmPFC tse tšehetsang tšebetso ena.

Boholo ba sele ea mantlha ho NAc e na le GABAergic medium spiny neurons (MSNs) e ka arotsoang ka palo ea D1-R le D2-R e hlalosang palo, hammoho e le ~ 90-95% ea li-neuron tsohle tsa (NNL al., ). Polelo e khethiloeng ea ChR2 ho palo e 'ngoe le e' ngoe ea batho ba NAc MSN e bontšitse hore ts'ebetso ea li-neuron tsa D1-R e ntlafalitse thuto ea moputso oa koae ka paradigm ea CPP, athe ts'ebetso ea li-neuron tsa D2-R e bile le litlamorao tse fapaneng (Lobo et al., ). Photostimulation ea liteishene tsa mPFC mokokotlong oa NAc e hlohlellelitse polelo ea ΔFosB ho li-neuron tsa D1-R, athe khetla ea NAc, polelo ea ΔFosB e kentsoe ka bobeli ho li-D1-R le D2-R subtypes (Lobo et al., ). Sena se fana ka maikutlo a hore kabo ea lietsahala tsa MPFC ho li-neuron tsa NAc e fapana bakeng sa khetla le mantlha (Lobo et al., ). Leha ho le joalo, sena se tla hloka hore se netefatsoe ke lirekoto tsa seleng e felletseng. Kameho e sebetsang ea mPFC ho li-projeke tsa NAc D1-R MSNs e bontšitsoe ke Pascoli et al. () ea bonts'itseng mokhoa oa ho nka lifoto tsa "frequency frequency" (1 Hz) o ile a khutlisa mokhoa o mong o sa kopaneng le koae oa "cocaine-induction" o kopantsoeng le "cxineine-indenti" o kopantseng cocaine-indeptic in D1-R neurons le sensomization ea locomotor. Haufinyane tjena, sehlopha sona seo se sebelisitse li-optogenetics ho senola boteng ba li-AMPA-R tse haellang tsa GluAX ho projeke ea ILC-NAc D2-R MSN khoeli ka mor'a ho itlhokofatsa ka koae (Pascoli et al., ). Photostimulation ea tsela ena ho 13 Hz, empa eseng 1 Hz, e khutlisitse liphetoho tsa synaptic kamora ho itaola le ho hlakola ho ts'oaroa hoa koae. Bangoli ba boletse hore ts'usumetso ea 13-Hz e hlokahala bakeng sa phello ena hobane sena se tsosa khatello ea maikutlo ea nako e telele ea mGluR, mohato o sebetsang oa ho tlosa synaptic GluA2 e haellang ea AMPA-Rs (Lüscher le Huber, ). Leha ho le joalo, ho fumana hona ho hanana le se boletsoeng ke Ma et al. (); (e tšohliloe ka holimo). Phapang ka ho khetheha ha potoloho (modumo oa optogenetic ea li-proion ho li-neuron tsa D1-R vs. likhakanyo ho li-neurons tsohle tsa NAc shell MSN) le ho "regocaine" ea koae li ka hlalosa litlamorao tse hanyetsitsoeng tse fumanoeng lithutong tsena.

Ntle le ho nka karolo ho tloheleng ho batla lithethefatsi, tsela ea mPFC-NAc e kenyelelitsoe ts'ebetsong e qobelloang ea joala e sa qobelloeng.. Photoinhibition ea dmPFC-NAc konokono ea mantlha e fokotse tšebeliso ea joala e kentsoeng ka tšusumetso ea maikutlo a fapaneng a maikutlo le mekhoa e fapaneng ea ho ja (Seif et al., ). Ts'ebeliso ea joala e ne e sa sitisoe ke ts'oaetso ea lifoto ha e sa phuthoa ka sephetho se seng, e fana ka maikutlo a hore tsela ena e tlare ho hlophisa likarolo tse hanyetsanang le bokhoba ba joala, tseo ho tsona hangata ho tsamaeang le likhohlano kapa phephetso (Tiffany le Conklin, ). Leha ho le joalo, liphetho tsena li hanana le ho fumana hore ts'oaetso ea Photoinhibition ea PLC e ntlafatsa tšebeliso ea koae e hananang le koae (Chen et al., ), ho fana ka tlhahiso ea hore PLC e ka laola ka mokhoa o fapaneng mokhoa oa ho itlopa joala le ts'ebeliso ea koae.

Ho kenya letsoho ha tsela ea mPFC-NAc ho fumana moputso le boitaolo ba lithethefatsi ho boetse ho fumanoe ka mekhoa ea optogenetic. Stuber et al. () e fumane hore ts'ebetso ea ts'ebetso ea "activation activation" ea mPFC-NAc (20 Hz) ha e ts'ehe ts'ebetso ea ts'ebetso ea boits'ebetso (likarabo tse sebetsang tse bakileng ts'usumetso ea leseli tse isitsoeng ho li-terminals tsa mPFC tsa Prescaptic ho NAc), leha e le taba ea ts'ebetso ea opereishene ea projeke ea mPFC e hlahisitse EPSC ho NAc. Phuputso e ileng ea latela e bontšitse hore liphoofolo li fumana mokhoa oa ho itšunya-tšunya oa tsela ea khetla ea mPFC-NAc ha maqhubu a ho hlohlelletsa a eketsoa ho 30 Hz (Britt et al., ). Ka hona, ho haptjoa ha glutamatergic ho tsoa ho MPFC ho NAc ho kanna ha tsosa spiking ea li-MSN le ho matlafatsa boits'oaro ka ts'ebetso e matla ea mPFC kapa ha maemo a DA ho NAc a phahame ka ho tšoana. Sebaka sa ts'usumetso se hlakileng ka har'a mPFC e kanna ea ba sa bohlokoa haholo ho fihlela sephetho sena, ho nahanoa hore ILC e nahanoa hore e na le projeke e matla ho khetla ea NAc ho feta PLC (Voorn et al., ). Joalo ka liphuputsong tse boletsoeng kaholimo polelo ea ChR2 e ne e sa rereloa ho ea ka kotloloho ho PLC kapa ILC, e ntse e tlameha ho tsejoa hore na phapang e teng ka har'a potways ea litsela tse peli tsa ho tsosa spiking ho li-NAc shell tsa MSN le ho matlafatsa boitšoaro ba ho batla moputso.

Tumellanong le mekhoa ea setso ea ho kena lipakeng, litlatsetso tsa ts'ebetso ea mPFC litabeng tsa bokhoba ba litheko li netefalitse karolo e tebileng ea karolo ena ho laola tšebeliso ea lithethefatsi le boits'oaro ba lithethefatsi le ho tšehetsa karohano e sebetsang tsamaisong ea dorsal-ventral ea mPFC. Ntle le moo, phetolo ea tsela e khethehileng e fane ka leseli le lecha mabapi le karolo ea BLA-PLC le mPFC-NAc. Ka ho khetheha, ts'usumetso ea optic ea li-terminal tsa PLC le li-axon tsa ILC maemong a kelello a hlobaetsang ho hlophisoa ha mantlha ea NAc mme khetla e bontšitse li-cocaine tse kenyellelitsoeng tseleng e ikhethang ea cocaine e ka khutlisetsoang morao ka ho sebelisa mekhoa e hlalositsoeng ea photoactivation frequency (Pascoli et al., , ; Ma et al., ). Sena se ka fana ka menyetla bakeng sa phetoho e kopantsoeng le DBS-mediated ea li-neuroadaptations tse tlisoang ke lithethefatsi ho lithethefatsi. Leha ho le joalo, joalo ka ha ts'usumetso ea motlakase e ama ts'ebetso ea li-neuronal ka mokhoa o sa khethang, ts'ebetso ea ho fetolela ho DBS e lula e lokela ho atameloa ka hloko mme e hloka lithuto tse ling.

Lipolelo tse qetellang

Ts'ebeliso ea morao-rao ea mahlale a optogenetic ho etsa lipatlisiso tsa li-neuroscience e tebisitse leseli mabapi le ts'ebetso ea mefuta e fapaneng ea potoloho bokong, mme e se e bile le karolo e kholo kutloisisong ea rona ea mPFC circry maemong a bophelo bo botle le a mafu. Manolo a optogenetic a etsa hore lipatlisiso tsa maemo a tsamaiso ea Causal mabapi le boits'oaro bo fapaneng ba boits'oaro ba methapo ho liphoofolo tse tsamaeang ka bolokolohi li lumelle ho kopanngoa ha Ka vivo 'me Ex vivo lirekoto tsa electrophysiological, tse neng li sa khonehe ka mekhoa ea setso ea ho kenella. Leha ho le joalo, ka mashome a lilemo, mokhatlo o moholo oa lipatlisiso o kenyelletsang mekhoa ea lesion, pharmacological le electrophysiological e fane ka tsebo ea bohlokoa mabapi le ho nka karolo ha mPFC lits'ebetsong tse fapaneng tsa kelello. Ho kopanyoa ha data ho fumanoeng ka mekhoa ena ea setso ea ho kenella le liphetoho tsa optogenetic li tla tsoela pele ho ba tsa bohlokoa bakeng sa kutloisiso ea rona ea mPFC circry le ho theha meetso e kopaneng ea ts'ebetso ea mPFC

Phapang e kholo ho arohaneng ha li-circonal tsa neuronal tse thusitsoeng ke theknoloji ea optogenetics ke ho laola ka ho toba merero ea neuronal kahare le lipakeng tsa boko. Mabapi le potoloho ea mPFC, sena se lebisitse kutloisisong e ntle ea khokahano ea intra-mPFC, karolo ea merero e kopanetsoeng le e sebetsang ea mPFC lits'ebetsong tsa kelello le mathata a kelello, le ho fihlela ho sibolloa ha palo e ncha ea sele ea GABAergic e nang le sebaka se selelele. monahano oa NAc (Lee et al., ). Ho feta moo, ka lebaka la khokahano e ntle ea li-optogenetics le Ex vivo physology ea boko slice, phapang e khethiloeng ea koae e hlahisitsoeng ho COC le lipalo tsa ILC ho NAc li hlakisitsoe (Ma et al., ), ho bonts'a bokhoni ba ho senyeha ha mekhoa ea mPFC e ikhethileng e sebelisang optogenetics.

Leha ho entsoe khatelo-pele e kholo, lintlha tse 'maloa li fumane tlhokomelo e nyane mme maemong a mang li hloka hore ntlafatso ea tekheniki e sebetsanoe hantle litekong tsa nako e tlang. Mabapi le palo ea baahi ba GABAergic interneuron ho mPFC, polelo ea opsin ho fihlela joale e se e lebisitsoe ho li-interneurons tsa PV, e siea karolo ea mefuta e meng e mengata ea lisele tsa GABAergic (mohlala, SOM +, lisele tsa calretinin, joalo-joalo) e sa imeloang. Ha mela le lipallo tsa "trans-driver" e ntse e eketseha, sena se bula mekhoa e mecha ea ho lekola karolo ea likarolo tse ling tsa mPFC ts'ebetsong ea kelello le mafu a kelello. Habohlokoa, lithuto tsa pele tsa "optogenetic" li bonts'itse boteng ba litlatsetso kahare ho GABAergic le palo ea batho ba seleng ea piramite e ka khetholloang feela ho latela mesebetsi ea bona e fapaneng nakong ea maemo a hlalositsoeng a boitšoaro (Little le Carter, ; Lekhotla et al., ). Mohlala, li-interneurons tsa PV li hokahantsoe le ts'ebetso ea ho sebetsa ea memori (Rossi et al., ), polelo ea likarabo tsa tšabo (Courtin et al., ), ho boloka tekano e nepahetseng ea E / I (Yizhar et al., ; Kvitsiani et al., ), le khokahano ea li-oscillations tsa gamma (Sohal et al., ; Sohal, ). Letšoao la "optogenetic tagging" la "neurons" le bonts'ang mosebetsi o eketsehileng nakong ea boits'oaro bo itseng e tla ba mohato oa bohlokoa o latelang ho qhekella ho se kenye letsoho hoa litho tsena tse ikhethileng tsa neuronal ho bontša ts'ebetso ea boitšoaro (Cruz et al., ). Polelo ea Opsin e tsamaisoang ke morekisi oa mofuta oa pele oa pele c-fos, letšoao le sebelisoang ka ho pharaletseng la tšebetso ea li-neuronal, ka li-neurons tsa hippocampal tse neng li sebetsa nakong ea maemo a ts'abo li bontša hore ena ke sepheo se ka fumanoang (Liu et al., ). Ho qaqisa data ea optogenetic hangata ho sitisoa ke ho sa tsejoe ka ho khetheha ha li-opsin ho li-subPions tsa MPFC. Ha ho ntse ho totobala ka ho hlaka hore libaka tsa dorsal le ventral tsa mPFC li na le mesebetsi e fapaneng 'me ka linako tse ling e hanyetsana (Heidbreder le Groenewegen, ; Van den Oever et al., ), ho tsamaisoa ha litheko tsa opsin ho tsoa maemong ana a hlalositsoeng ho bohlokoa haholo. Ntle le moo, tsoelo-pele ea tekheniki e lumellang ho lebisoa ha li-opsin ho likarolo tse ling kahare ho mPFC e ka ba ea bohlokoa bo boholo ha ho fanoa ka tšebeliso e rarahaneng ea li-neuronal- le subregion-e hlalositsoeng ka kutlo ea neuronal ea li-neuron tsa mPFC (Groenewegen et al., ; Voorn et al., ; Hoover le Vertes, ).

Hajoale, li-FDA tse ngata tse amohetseng litlama tsa bongaka li shebile li-protein tsa G-protein tse bokellaneng bokong (Lee et al., ). Kahoo, ho ntlafatsa temohisiso karolong ea nakoana ea li-receptor tsena ho linaha tse ikhethang tsa boits'oaro ho tla thusa haholo kalafong ea mafu a kelello ka rialo, le litlhare tse khethehileng tse khethiloeng. Moralo oa li-opsin o kenyang chimera ea opsin e kentsoeng sebakeng sa boteng sa G-protein e kopaneng receptor (optoXR), e etsa hore ho hlongoe lipotso ho kenyelletsoang ha protocol ea G-protein e kopantsoeng ho bonts'a li-cascades tse nang le qeto e phahameng ea spatiotemporal (Airan et al., ). Ho fihlela hajoale, li-optoXR ha li so sebelisoe ho ithuta ho kenya letsoho likhakanyo tse ikhethang tsa letšoao la ts'ebetso ea potoloho ea mPFC, empa li ka ba molemo haholo ho hlaloseng karolo ea phetoho e bonts'itsoeng ea protheine ea G-protein ho mafu a mafu a kelello (Hearing et al., ; Luján et al., ). Ntle le moo, nts'etsopele e ncha lefapheng la theknoloji ea chemogenetic (mohlala, DREADD: Designer Receptors Expusiveely activated by Designer D drug) e tla kenya letsoho hape ho arohaneng ha potoloho ea mPFC le ho tsebahatsoa ha lipehelo tse ka rekisoang (Sternson le Roth, ).

Tšebeliso ea li-optogenetics bathong bakeng sa kalafo ea mathata a methapo ea kutlo e builoe ka mokhoa o pharaletseng (Peled, ; Kumar et al., ; Touriño et al., ) Leha ho le joalo, ts'ebeliso ea bongaka ea theknoloji ea optogenetics ke, tsebong ea rona, ha e sa khonehe. Ho atolosa mekhoa ea optogenetic ho mefuta e fetang litoeba e sebelisitsoe feela ka mokhoa o sireletsehileng, ka mokhoa o sireletsehileng le ka mokhoa o nepahetseng ho rhesus macaque, tekanyo eo eseng ea motho (Han et al., ; Diester et al., ; Han et al., ; Cavanaugh et al., ; Gerits et al., ; Jazayeri et al., ). Boithuto bo eketsehileng le liteko tsa tleliniking li tla hlokahala ho hlahisa ka mokhoa o sireletsehileng le ho sebelisa li-opsin ka bokong ba motho. Kahoo, ntle le ts'episo e phahameng ea kalafo ea bongaka, hajoale optogenetics e lokela ho nkuoa e le lebokose le matla la lisebelisoa tsa ho hlapolla methapo ea methapo mefuteng ea liphoofolo ea matšoao a amanang le lefu le ho fumana le ho nchafatsa lipheo tsa kalafo ea meriana le ea DBS.

Khohlano ea polelo ea thahasello

Bangoli ba bolela hore lipatlisiso li ne li etsoa ka ho se be le likamano leha e le life tsa khoebo kapa tsa lichelete tse ka nkoang e le khohlano e ka 'nang ea e-ba le thahasello.

lumela hore baa fokola

Mariana R. Matos e tšehelitsoe ke EU MSCA-ITN CognitionNet (FP7-People-2013-ITN 607508). August B. Smit, Sabine Spijker o tšehelitsoe karolo e 'ngoe ke thuso e fuoang NeuroBasic Pharmaphenomics Consortium. Danai Riga ka karolo e tšehelitsoe ke Letlole la ho netefatsa maikutlo la NCA (Sabine Spijker). Michel C. Van den Oever o tšehelitsoe ke chelete ea ZonMw VENI (916.12.034) le thuso ea Hersenstichting Nederland (KS 2012 (1) -162).

Lintho tse ling tse eketsehileng

The Supplementary Material bakeng sa sehlooho sena se ka fumaneha Inthaneteng ka: http://www.frontiersin.org/journal/10.3389/fnsys.2014.00230/abstract

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