Ketso ea ho leka-lekanya ho hlasela ka ho lemalla lithethefatsi: mesebetsi e tobileng ea tsela e tobileng le e sa tobang ea spiny neurons (2011)

Front Neuroanat. 2011; 5: 41. Doi: 10.3389 / fnana.2011.00041. Epub 2011 Jul 18.

Lobo MK, Nestler EJ.

mohloli o moholo

Lekala la Fishberg la Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine New York, NY, USA.

inahaneloang

Striatum e bapala karolo ea bohlokoa ho loants'eng litlamorao tse bohloko le tse sa foleng tsa lithethefatsi tse lemalloang, ka lithethefatsi tsa tlhekefetso tse bakang liphetoho tsa nako e telele tsa limolek'hule le tsa cellular ho dorsal striatum le nucleus bokella (ventral striatum). Leha ho na le leruo la lipatlisiso mabapi le liketso tsa tlhekefetso ea lithethefatsi tse sebelisitsoeng hampe ho striatum, ho fihlela haufinyane, likarolo tse ikhethang tsa li-subtypes tse peli tse kholo tsa striatum tsa li-spiny neurons tse mahareng (MSNs) ho lemalleng lithethefatsi li ntse li le thata. Tsoelo-pele ea morao-rao litheknoloji tse ikhethang tsa mofuta oa sele, ho kenyeletsoa le litoeba tsa moqolotsi oa litaba tsa fluorescent, litoeba tsa transgenic, kapa kokota, le phetisetso ea liphatsa tsa lefutso tse fetisitsoeng ke vaerase, li tsoetse pele lebaleng ho fihlela kutloisiso e felletseng ea li-subtypes tse peli tsa MSN liketsong tsa nako e telele tsa lithethefatsi ea tlhekefetso. Mona re lekola tsoelo-pele ea ho hlalosa monehelo o ikhethileng oa limolek'hule le ts'ebetso ea li-subtypes tse peli tsa MSN mabapi le ho lemalla bokhoba.

Selelekela

Lithethefatsi tsa tlhekefetso li fana ka liphetoho tse ka bang teng ka sebopeho sa limolek'hule le tsa cellular ho dorsal striatum (dStr) le ventral striatum (nucleus accumbens, NAc), 'me liphetoho tse ngata li etsahala li-kati tsa spiny neurons (MSNs), li-neurons tsa projeke tsa mantlha ho dStr le NAc, e ak'haonte ea 90-95% ea methapo eohle ea kutlo libakeng tsena. Leha ho le joalo, bafuputsi ho fihlela haufinyane ba sa khone ho hlalosa ka ho hlaka karolo e ikhethang ea likarolo tse peli tsa MSN liketsahalong tse amanang le bokhoba. Li-subtypes tse peli tsa MSN li khethollotsoe ka ho ruisa ha tsona dopamine receptor 1 (D1) kapa dopamine receptor 2 (D2) le mefuta e meng e mengataGerfen le Monyane, 1988; Gerfen et al., 1990; Le Moine et al., 1990, 1991; Bernard et al., 1992; Ince et al., 1997; Lobo et al., 2006, 2007; Heiman et al., 2008; gensat.org) le ka likhakanyo tsa bona tse ikhethang ka tsela ea cortico-basal ganglia (tsela e tobileng; Gerfen, 1984, 1992). Mosebetsi oa pele o khothalelitse hore lithethefatsi tsa tlhekefetso li na le tšusumetso ho D1+ Li-MSN, ka tšebeliso ea litsebi tse ngata tsa dopamine receptor agonists le bahanyetsi ba fanang ka leseli la bohlokoa mabapi le likarolo tse sebetsang le tsa limolek'hule tsa MSN ka 'ngoe litloaelong tsa moputso oa lithethefatsi (Boithati, 2010). Leha ho le joalo, mekhoa ea hona joale ea mofuta oa sele, ho kenyelletsa litoeba tsa fluorescent tse hlahisang GFP tlasa D1 kapa D2 li-chromosomes tsa maiketsetso (BACs; Gong et al., 2003; Valjent et al., 2009; gensat.org), mehlala ea litoeu tse nang le maemo a joalo ka tšebeliso ea litoeba tse tsoang ho tetracycline-regigible indgenible transgenicChen le al., 1998; Kelz et al., 1999), le litoeba tsa transgenic tse hlalosang Cre-recombinase e sebelisang D1 kapa D2 Li-BAC, li-chromosome tsa maiketsetso (YACs), kapa litoeba tse kokotang (Gong et al., 2007; Lemberger et al., 2007; Heusner et al., 2008; Parkitna et al., 2009; Valjent et al., 2009; Bateup et al., 2010; Lobo et al., 2010; gensat.org) le phetiso ea mofuta o ikhethileng oa mofuta o amanang le vaerase (Cardin et al., 2010; Hikida et al., 2010; Lobo et al., 2010; Ferguson et al., 2011), li fane ka leseli le lecha le hlakileng mabapi le ho kenella ka tlase ha "molek'hule o mong le o mong oa MSN le taolo ea bona ka lithethefatsi tsa tlhekefetso (Lethathamo 1).

TABLE 1
www.frontiersin.orgLethathamo 1. Litlamorao tsa ho fetoloa hoa mofuta o khethehileng oa liphatsa tsa lefutso ho D1+ le D2+ Li-MSN ka mefuta ea bokhoba ba lithethefatsi.

Liphumano tsa morao-rao li tšehetsa sephetho sa karolo e etelletseng pele ea D1+ Li-MSN ha li hlahisa phello e matlafatsang le e khahlisang ea lithethefatsi tsa tlhekefetso, ka liphetoho tse matla haholo tsa limolek'hule tse hlahang li-MSN tsena. Mohlala, ho pepesehela ho li-psychostimulants ka matla ho etsa hore limolek'hule tse ngata tse saenneng ho kenyeletsa FosB, ERK, c-Fos, le Zif268 ho D1+ Li-MSN, ha li ntse li phetoa ka mokhoa o ikhethileng oa koae ΔFosB le li-converter GABA receptor le li-Channel tse ling tsa ion li ipeha ka mofuta ona oa sele.Robertson et al., 1991; Young le al., 1991; Berretta et al., 1992; Cenci et al., 1992; Moratalla et al., 1992; Hope et al., 1994; Bertran-Gonzalez et al., 2008; Heiman et al., 2008). Ntle le moo, ho senya kapa ho hlahisa limolek'hule tse ikhethang, tse kang ΔFosB, DARPP-32, kapa Nr3c1 (glucocorticoid receptor) ho D.1+ Li-MSN ka tloaelo li etsisa boits'oaro bo amanang le lithethefatsi bo bonoang ha liphetoho tsena li etsoa ka tsela e sa amaneng le sele, ha li ntse li senya mefuta e joalo ho D2+ Li-MSN hangata li baka karabelo e fapaneng (Fienberg et al., 1998; Kelz et al., 1999; Deroche-Gamonet et al., 2003; Zachariou et al., 2006; Ambroggi et al., 2009; Bateup et al., 2010). Leha ho le joalo, re ke ke ra fana ka tlhahiso ea bohlokoa ea D2+ Li-MSN ha li ikamahanya le lithethefatsi tsa tlhekefetso, hobane ho pepesetsoa hoa koae ho fetola polelo ea mofuta oa li-subtypes ka bobeli ba MSN (Heiman et al., 2008) le D2-receptor agonists le antagonists ba fana ka matla ho litla-morao tsa boitšoaro (Boithati, 2010). Ka sebele, lipatlisiso tsa morao-rao li bonts'a hore liphetoho tsa limolek'hule ho D2+ Li-MSN ka mokhoa o fetohang li fetola karabelo ea phoofolo ka lithethefatsi tsa tlhekefetso (Lobo et al., 2010). Liphumano tsa morao-rao li bonts'a tahlehelo ea TrkB (receptor ea BDNF) ho D2Li-MSN li hlahisa karabelo e tšoanang ea boitšoaro ho koae ka ho ba kantle ho TrkB ho tsoa ho NAc, ho bonts'a ka lekhetlo la pele karolo e ikhethileng ea tsela ea molek'hule ho D2+ Li-MSN ha li buisana le litlamorao tsa lithethefatsi tsa tlhekefetso.

Kamora nako, lingoliloeng tsa morao-rao li senola hore li-MSN tse peli li fana ka litlamorao ho boits'oaro bo amanang le lithethefatsi, moo ts'ebetso ea D e sebetsang1+ Li-MSN kapa thibelo ea D2+ Li-MSN li ntlafatsa maikutlo a phoofolo ho sehlahisoa sa tlhekefetso (Hikida et al., 2010; Lobo et al., 2010; Ferguson et al., 2011). Liphumano tsena li tsamaisana le likarolo tse hanyetsanang tsa li-MSN tse peli le litsela tsa tsona tse tobileng ho tsela e sa tobang ho basal ganglia ka boits'oaro ba motor (Alexander et al., 1986; Albin le al., 1989; Graybiel, 2000; Kravitz et al., 2010). Lingoliloeng tsena tsa morao-rao li lumellana le mohopolo o akaretsang oa hore dopaminergic neurotransication, e hlahisoang ke lithethefatsi tsohle tsa tlhekefetso, e thusa ts'ebetso ea glutamatergic ea D1+ Li-MSN ha li thibela ts'ebetso ea glutamatergic ea D2+ Li-MSN ka liketso tsa tsona ho D1 vs. D2 dopamine receptors (Setšoantšo 1). Thutong ena, re shebana le tsebo ea hona joale ea molek'hule o ikhethang o bonts'itsoeng ke li-subtypes tsena tse peli tsa MSN mabapi le likarolo tsa bona tse sebetsang le likarabo tsa lithethefatsi tsa tlhekefetso.

Tšoantšiso 1
www.frontiersin.orgSetšoantšo sa 1. Lithethefatsi tsohle tsa tlhekefetso li eketsa ho bonts'a dopamine ho striatum, e ka khethollang ka mokhoa o fapaneng ts'ebetso ea glutamatergic ho li-subtypes tse peli tsa MSN. Haholo-holo, koae e sebetsa ho phepelo ea dopamine ho thibela phetisetso ea dopamine liteisheneng tsa methapo ea methapo ea methapo ea methapo ea methapo. Ts'ebetso ea Gs/olf hammoho le D1 li-receptors li ntlafatsa tšebetso ea PKA le li-alter Ca2+ le K+ boitšoaro ho ntlafatsa "boemo bo holimo" ba li-glutamate ho li-MSN tsena. Ka lehlakoreng le leng, ts'ebetso ea Gi/Go D2-receptors e fokotsa tšebetso ea PKA le li-alter Ca2+Na+, le K+ boits'oaro ba ho fokotsa "glutamate" ea boemo bo phahameng. Sena se khutlisetsa li-MSN tsena sebakeng sa tsona sa ho phomola.

Dopamine Receptor Signaling ho D1 vs. D2 Li-MSN

Joalokaha ho se ho hlokometsoe, lithethefatsi tsohle tsa tlhekefetso li kenya ts'ebetso ea dopaminergic ho li-NAc le likarolo tse amanang le bokong ba leoto (Volkow et al., 2004; Bohlale, 2004; Nestler, 2005). Mohlala, li-psychostimulants tse kang cocaine kapa amphetamine li sebetsa ka kotloloho tseleng ea moputso oa dopaminergic ka ho kena-kenana le transporter ea dopamine: cocaine e thibela transporter ebe amphetamine e khutlisa transporter, liketso tseo ka bobeli li fella ka ho theha dopamine ka sehokela se ka etsang hore dopamine e theohe tlaase. li-receptor ho li-neurons tse hlotsoeng (Setšoantšo 1). Li-MSN tse peli li khethollotsoe haholo ka ho ruisa ha bona D1 vs. D2Barekisi ba lithuto le ha lithuto tsa RT-PCR li sa sebetse li senola hore D1+ Li-MSN li bontša maemo a tlaase a D2-e amohelang, joaloka3 le D2+ Li-MSN li bontša maemo a tlaase a D1-e amohelang, joaloka5 (Surmeier et al., 1996). Li-MSN tse peli li hloka ho ts'oaroa ha glutamatergic ho tsamaisa mosebetsi oa neural; dopamine ka mokhoa o fapaneng e fetolela likarabo tsena tse sebetsang ka ho susumetsa li-subtypes tse ikhethang tsa dopamine: ka ho feto-fetoha ka mokhoa o hlakileng oa ho kenella ha glutamatergic ka D1 receptor signaling ka Gs kapa Golf, e hlohlelletsang marang-rang a adenylyl a lebisang tšebetsong ea PKA, athe dopamine hampe e kenya phetoho ena ka D2-receptor e bonts'a ka Gi le Go e thibelang cymbase ea adenylyl e bakang tšebetso ea PKA e fokotsehileng (Surmeier et al., 2007; Gerfen le Surmeier, 2011). 'Nete ke hore setsi se seng le se seng sa marang-rang se fana ka litlamorao tse matla litseleng tse ngata tse tlase tsa noka. Phomolong, li-subtypes tse peli tsa MSN hangata ha li na letho, li ho seo bafuputsi ba se bitsitseng boemo bo tlase. Ts'ebetso e thabisang ea glutamatergic synaptic e ka lokolla li-MSN ho tloha boemong bona ba tlase mme ea li fetisetsa boemong bo senyehileng haholoanyane (mmuso-o moholo). Dopamine ka mokhoa o fapaneng e feto-fetoha le phetoho e nyakallisang ea glutamatergic ho boemo bo phahameng. D1 ts'ebetso ea PKA e ntlafatsa Cav1 L-mofuta Ca2+ tšebetso ea seteraete, e fokotsehile somatic K+ ts'ebetso ea seteishene, 'me e theola Cav2 Ca2+ liteishene tse laolang ts'ebetso ea Ca2+ its'epahalle, boits'oaro bo nyane K+ (SK) liteishene, ho fella ka hore ho be le spark e ngata li-MSN tsena (Surmeier et al., 2007; Gerfen le Surmeier, 2011). Ho fapana le hoo, D2 ho supa ho thibela phetoho ea boemo ba mmuso, ka ho etsa joalo ho thibela spiking e matla, ka ho fokotsa Cav1 L-mofuta oa Ca2+ ts'ebetso ea seteishene le Nav1 Na+ tšebetso ea seteishene ha a ntse a eketsa K+ marang-rang (Surmeier et al., 2007; Gerfen le Surmeier, 2011;; Setšoantšo 1). Liphetoho tse fapaneng joalo ho li-MSN tse peli li fana ka maikutlo a hore ho eketseha ha dopamine ho hlahisoang ke lithethefatsi tsa tlhekefetso ho lokela ho matlafatsa ts'ebetso ea glutamatergic ea D1+ Li-MSN le ho fokotsa ts'ebetso ea glutamatergic ea D2+ Li-MSN. 'Nete ke hore likarabo tse joalo li fapane haholo ebile li rarahane ka mabaka a sa utloisisoeng hantle. Sehlooho sena se tla tšohloa ka tlase.

Karolo ea li-receptor tsa dopamine tlhekefetsong ea lithethefatsi e rarahane ebile hangata ha e khonehe (Boithati, 2010). Ho na le lingoliloeng tse ngata tse mabapi le karolo ea D1 le D2-receptor agonists le bahanyetsi ba ho fetolela thepa e ruisang le ho itaola lithethefatsi tsa tlhekefetso, leha ho le joalo, liphetho li fapana ho latela mofuta oa agonist / antagonist o sebelisitsoeng, mofuta oa ho fana (systemic vs. brain mkoa o ikhethang), le nako ea nako ea kalafo (Boithati, 2010). Liphetho tse joalo li soabisoa hape ke litlamorao tse sa amaneng le litšebeletso, joalo ka monehelo oa pre-synaptic D2Barekisi ba tsoang ho VTA kapa boteng ba D1 li-receptors libakeng tse ling tse ngata tse nang le maoto, le tlhokeho ea maemo a agonists / antagonists li sebelisitsoe hammoho le polelo ea D1-ka tšoana le D2Li-receptors tse kang li-subtypes ka bobeli tsa MSN joalokaha ho boletsoe pejana. Ka kakaretso, ho nahanoa hore D1 li-receptors li bapala karolo ea mantlha mehloling e meholo ea meputso ea lithethefatsi tsa tlhekefetso, athe D2Barekisi ba bapala karolo ea bona molemong oa ho batla lithethefatsi (Boithati le al., 1996; Boithati, 2010). Lithuto le D1 receptor le D2litoeba -receptor knockout fana ka leseli le itseng mabapi le karolo ea li-receptors tsena ho li-MSN tse peli. D1 knockout litoeba li hlahisoa ka mokhoa o phollotsoeng oa liphatsa tsa lefutso tsa pele (IEGs) c-Fos le Zif268 ha li araba koae, karabelo e fokotsehileng mesebetsing e amanang le psychostimulant empa e se na liphetoho lipakeng tsa mofuta oa cocaine e nang le maemo a phetoho (CPP) - tekanyo e sa tobang moputso oa lithethefatsi, le ho fokotsa ts'ebetso ea k'hok'heine le litekanyetso tsa ethanol (Miner et al., 1995; Drago et al., 1996; Crawford et al., 1997; El-Ghundi et al., 1998; Caine et al., 2007). D2 litoeba tse tsoang lefatšeng le leng le leng li ile tsa fokotsa litlamorao bakeng sa opiate le cocaine hammoho le tšebeliso ea ethanol e fokotsehileng empa ha ho na phokotso ea ho tsuba koae (Maldonado et al., 1997; Cunningham et al., 2000; Risinger et al., 2000; Caine et al., 2002; Chausmer et al., 2002; Elmer et al., 2002; Welter et al., 2007). Lintlha tse joalo li tšehetsa likarolo tsa bohlokoa bakeng sa D1 le D2- Barekisi ba li-MSNs tse peli maemong a mangata a tlhekefetso ea lithethefatsi, leha ho le joalo, li-knockout ha li bue ka mokhoa o hlakileng mme li etsahala kapele ho nts'etsopele, ka hona motho a ke ke a ahlola likarolo tse ling tsa boko le mefuta ea lisele le lintlha tsa nts'etsopele ho hanana le boits'oaro bona. Qetellong, maemo a theohileng a D2/D3 receptors in striatum, joalo ka ha ho bonoa ke monahano oa kelello, e se e le letšoao le tloaelehileng la ho lemalla bakuli ba batho haholo-holo nakong ea ha motho a khaotsa (Volkow et al., 2009). Liroko tse amohelang phetiso ea lefutso e fetisoang ka bongata2Barekisi ba mananeo a NAc a bonts'a koae le ho itšebelisa ka "Thanos et al., 2004, 2008). Lithuto tsena ha lia etsoa ka mokhoa o ikhethileng oa sele, ka hona re ke ke ra tseba hore na phello ea D e ka ba efe2-receptor overexpression e susumetsang D1+ Li-MSN. Pokello ena ea data e hatisa tlhokahalo ea ho fetela lits'ebetsong tse khethiloeng haholoanyane, ho kenyeletsoa mofuta oa sele, mofuta o ikhethileng, esita le litla-morao tse ikhethileng tsa li-dopamine receptors ho hlakisa likarolo tsa bona tsa ts'ebetso ho li-subtypes tse peli tsa MSN tšebelisong ea lithethefatsi.

Qetellong, ho tlalehiloe haufinyane hore D2-GFP homozygote BAC transgenic litha e hlahisa maemo a phahameng a polelo ea D2-receptor in striatum and sensitivity e ntlafalitsoeng ea boits'oaro le dopamine ho supa ho D2 agonists. Ho feta moo, homozygotes le hemizygotes li bonts'a likarabo tse sa nepahalang tsa boitšoaro ho koae (Kramer et al., 2011). Boithuto bona bo totobatsa tlhoko ea ho etsa sebopeho se hlakileng sa D1 le D2 moqolotsi oa litaba oa fluorescent le mela ea mokhanni oa Cre. Leha ho le joalo, boholo ba data bo bokelletsoeng thupelong ena bo sebelisitse homozygotes, e seng mokhoa o nepahetseng oa tlhahlobo ho tloha 5-10% ea ho kenella ha transgene ho fella ka liphetoho tse kenyellelitsoeng (Meisler, 1992); ka hona, mofuta oa hemizygote ke mofuta o tšepahalang ka ho fetisisa oa tlhahlobo. Ntle le moo, thuto ena ha ea ka ea sebelisa li-littermate wildtype control empa e sebelisitse li-control tse ka morao (Swiss Webster) e fumanoeng ho Taconic, ha mela ea bona ea transgenic e fumanoe ho tsoa ho GENSAT le MMRRC. Qetellong, sehlopha se seng se bonts'itse likarabo tse tloaelehileng tsa cocaine locomotor ho D2-GFP hemizygotes (Kim et al., 2011). Kahoo, lithuto tsa nako e tlang li sebelisa li-control tse nepahetseng le li-genotypes tse nepahetseng li tlameha ho etsoa ho supa ka botlalo mela e mengata e fapaneng ea mofuta oa sele e fumanehang.

Glutamate le GABA Signaling ho D1 vs. D2 Li-MSN

Li-neurons tsa mahareng tsa "spiny" li fumana ho kenngoa ha glutamatergic ho tsoa libakeng tse ngata tsa boko ho kenyeletsa preortalal cortex, amygdala, hippocampus, le tlhahiso ea GABAergic e tsoang lipakeng tsa lehae mme mohlomong le lipeeletso tse kopaneng tse tsoang ho li-MSN tse ling. Ts'ebetso ea thabo le matla a thibelo ea mathata a marang-rang a li-MSN ha ho na pelaelo ea bohlokoa bakeng sa ho laola mmuso o lemaletseng lithethefatsi, 'me hona joale ho na le lingoliloeng tse ntseng li eketseha ka mekhoa e rarahaneng eo lithethefatsi tsa tlhekefetso li fetisang lefu la neurotamatergic neurotransication haholo-holo ho NAc (Pierce et al., 1996; Thomas et al., 2001; Beurrier le Malenka, 2002; Kourrich et al., 2007; Bachtell le Boithati, 2008; Bachtell et al., 2008; Conrad et al., 2008; Kalivas, 2009; Wolf, 2010). Le ha ho nahanoa hore li-MSN li teng ka har'a maemo a thibeloang tlas'a maemo a tlase a ts'ebetso ea ho khanna ea glutamate ea mefuta ena e 'meli ea cell, ho na le leseli le fokolang mabapi le taolo e ikhethileng e etsahalang ho D.1 vs. D2 Li-MSN.

OFosB oxpxpression ho D1+ Li-MSN (bona ka tlase bakeng sa lintlha tse ling) li ntlafatsa litlamorao tse khahlisang tsa koae le ho eketsa maemo a Ca2+-unermeptable glutamate receptor subunit, GluR2, ho NAc. Ntle le moo, phetiso ea lefutso e fetisitsoeng ke vaerase ea GluR2 ho NAc ka ho tšoanang e ntlafatsa litlamorao tsa cocaine (Kelz et al., 1999). Leha ho le joalo, ha ho tsejoe hore na ho kenngoa ha GluR2 ho bonoa ho arabela ΔFosB overexpression ho D1+ Li -MSN li boetse li bua ka li-neuron tsena, 'me bongata ba vaerase ea GluR2 ha bo khethoe ke mofuta oa cell, ka hona re ke ke ra fana ka sephetho se tobileng mabapi le ts'ebetso ea GluR2 ho li-MSN tsena tse peli moputsong oa lithethefatsi. Heusner le Palmiter (2005) e hlahlobile karolo ea boitšoaro ba NMDA glutamatergic boits'oarong ba koae ka ho hlahisa subunit ea NR1, e nang le phetoho pore e fokotsang calcium flux, ka boikhethelo ho D1+ Li-MSN. Sehlopha sena se bontšitse hore ho haella ha boitšoaro ba NMDA ho D1+ Li-MSN li thibela ts'ebetso ea k'hok'heine ea k'hok'heine le k'hok'heine ea koae, e totobatsang tlhokahalo ea ho saena ha NMDA ho D1+ Li-MSN bakeng sa litlamorao tse khahlisang le tse khahlang tsa koae.Heusner le Palmiter, 2005). Ntle le moo, haufinyane tjena ho fumanoe hore o khenekisa subunit ea NR1 ho D1+ Li -MSN li bonts'a maikutlo a amphetamine mme mokhoa ona oa phenotype o pholositsoe ka ho khutlisetsa subunit ea NR1 ho D1+ Li-MSN ka ho khetheha ho NAc (Beutler et al., 2011). Kamora nako, ho kokota ha setsi sa mGluR5, re sebelisa tšitiso ea RNA, ho D1+ Li-MSN ha li na tšusumetso ho litheko tsa pele tsa moputso oa cocaine empa li fokotsa ho khutlisetsoa hoa cueine ka lebaka la ho batla koae (Novak et al., 2010). Ha data tsena li senola likarolo tse qobellang bakeng sa lets'oao la glutamatergic ho D1+ Li-MSN, mosebetsi oa nako e tlang oa hlokahala ho ithuta lits'ebetso tsa glutamatergic ho D2+ Li-MSN. Patlisiso ea nako e tlang e boetse e lokela ho lekola hore na ho feto-fetoha ha methapo ea li-glutamate receptor ho li-subtypes tse peli tsa MSN ho ama joang liphetoho tse bonoang li -aptaptic tse bonoang ho NAc kamora lithethefatsi tsa tlhekefetso (Dietz et al., 2009; Russo et al., 2010), haholo liphetoho tse hlokometsoeng tse hlokometsoeng kamora ho pepesetsoa hoa koae ka mokhoa o ikhethileng ho D1+ Li-MSN (Lee le al., 2006; Kim et al., 2011) e kanna ea amahanngoa le keketseho ea maqhubu a manyenyane a monate a liphihlelo tsa postynaptic tse hlokometsoeng ho D1+ Li-MSN (Kim et al., 2011). Ho khahlisang, tlhahiso ea ΔFosB ho D1+ Li-MSN li amana ka kotlolloho le liphetoho tse joalo tsa dendritic ka mor'a cocaine e sa foleng.Maze et al., 2010).

Ho fapana le glutamate, ho na le khaello ea lipatlisiso mabapi le ts'ebetso ea GABA ho li-MSN tse peli ka mefuta ea ho lemalla, ho makatsang ha ho nahanisisa ka li-ethanol le benzodiazepines ho ntlafatsa litlamorao tsa GABA mme li-MSN tse peli li fumana lipehelo tse matla tsa GABAergic joalo ka ha ho boletsoe kaholimo. Ho boetse ho na le bopaki bo bongata bo supang thibelo e ntlafalitsoeng ho NAc bonyane kamora ho pepesetsoa ha koae e sa foleng.White et al., 1995; Batho et al., 1998; Zhang et al., 1998; Thomas et al., 2001; Beurrier le Malenka, 2002). Heiman et al. (2008) ba etsa lipatlisiso tsa liphatsa tsa lefutso tse phahameng ho li-MSN tse peli kamora ho pepesetsoa ha koae hape, ka ho khahlisang, ke ts'ebetso e fetotsoeng ea tlhaho haholo ho D.1+ Li-MSN li ne li saena GABA. Haholo-holo ho ne ho e-na le ts'ebetso e matla ea GABAA receptor e tsamaisa Gabra1 le Gabra4 hammoho le GABAB receptor subunit Gabrb3, 'me sehlopha sena se fumane hore cocaine e sa foleng e eketsa khafetsa maqhubu a manyane a mahlaseli a "gabaergic mini inhibitory postynaptic currents" (mIPSCs) ho D1+ Li-MSN (Heiman et al., 2008). Ka lehlakoreng le leng, sehlopha se seng haufinyane se bonts'itse hore cocaine e sa foleng e baka karabelo e fapaneng le khaello e fokotsang khafetsa le bophahamo ba li-MIPC ho D1 + MSNs (Kim et al., 2011). Leha ho le joalo, sehlopha sa morao-rao se bontsitse ho fokotseha ha lereho ho D1+ Li-MSN ka mor'a koae e sa foleng ea cocaine, e ka ba sesupo sa molumo oa ntlafatso oa GABA ebile e lumellana le tlhahlobo ea tšimo ea inhibition e ntlafalitsoeng ho NAc kamora ho pepesetsoa koae e sa foleng. Ho feta moo, liphapang tse joalo lipakeng tsa lihlopha tsena ka bobeli li ka bakoa ke nako ea ho pepesetsoa koae le ho khaotsa. Ka kakaretso, ho na le tlhoko ea ho ithuta ts'ebetso ea glutamatergic le GABAergic ho li-MSN tse peli ho arabela lithethefatsi tsa tlhekefetso mme tšimo e se e na le lisebelisoa tse ka etsang hore mofuta o joalo oa mofuta oa sele le mofuta o ikhethang o khonehe.

Tse Ling tse amohelang Receptor ho D1 vs. D2 Subtypes tsa MSN

Li-MSN tse peli li ruisitsoe ka mokhoa o fapaneng li-receptor tse ling tsa G-protein tse kenyelletsoeng ho kenyelletsa li-receptor tsa dopamine. D1+ Li-MSN li bontša maemo a holimo a acetylcholine muscarinic receptor 4 (M4; Bernard et al., 1992; Ince et al., 1997) le D2+ Li-MSN li ruisitsoe ho adenosine receptor 2A (A2A; Schiffmann et al., 1991; Schiffmann le Vanderhaeghen, 1993) le li-receptor X tse nang le protheine ea GNUMX (Gpr6; Lobo et al., 2007; gensat.org). M4 e kopantsoe le Gi / o, e neng e tla hlahisa karabelo e fapaneng, ha e bapisoa le D1 li-receptors, ho D1+ Li-MSN ka ho thibela tšebetso ea cAMP / PKA. Ka 'nete, D1+ MSN khetha M4 Ho kokota ho bontšitse maikutlo a ntlafalitsoeng a boitšoaro ho cocaine le amphetamine (Jeon et al., 2010). Ntle le moo, lithuto tsa morao-rao tse sebelisang receptor ea moetsi li hlahisoa feela ke lithethefatsi tsa maiketsetso (DREADDs) li bonts'itse ts'ebetso ea DREADD Gi / o-e kopantsoeng le motho M4 receptor (hM4D) ho D1+ Li-MSN li fokolisitse maikutlo a boitšoaro ho amphetamine, ka karabelo e fapaneng e bonoang ho D2+ Li-MSN (Ferguson et al., 2011). Lintlha tse joalo li senola karolo e phehisang ea M4 li-receptors ho D1+ Li-MSN ts'ebelisong ea lithethefatsi. Joalo, ho tloha hM4D receptor e na le monyetla oa ho thibela li-MSN tsena, tlhaiso-leseling e fana ka leseli mabapi le phello ea mesebetsi e fetotsoeng ea li-MSN tsena ka ts'ebeliso e mpe ea lithethefatsi, e tla buisanoa ka tlase ka tlase.

Ka bobeli A2A le Gpr6 li kopantsoe le Gs/Golf protheine, e hlahisang karolo ea bona ho hanyetseng D2-receptor ho D2+ Li-MSN. Ka sebele, tšusumetso ea A2A li-receptors li bontšitsoe hore li fokotsa nts'etsopele le polelo ea maikutlo a koae (cocaine sensitization)Filip et al., 2006), e sitisa ho qala ts'ebetso ea "cocaine"Knapp et al., 2001), le ho hanyetsa ho khutlisetsoa hoa koae e batlang e khothalelitsoe ke koae, D2Tšusumetso e mpe, kapa likhakanyo tsa boemo ba koae (Bachtell le Boithati, 2009). Joalokaha Gpr6 le eona e ruisitsoe ho D2+ Li-MSN (Lobo et al., 2007), karolo ea eona ea ts'ebetso ea ts'ebetso ea striatum e lokela ho hlahlojoa. Ho fihla joale, e bontšitsoe hore e susumetsa ho ithuta ho matla (Lobo et al., 2007) empa karolo ea eona mefuteng ea tlhekefetso ea lithethefatsi e ntse e sa tsejoe.

Cannabinoid receptor 1 (CB1) e hlahisoa ka mokhoa o hlakileng ho pholletsa le tsamaiso ea methapo e kholo (Mackie, 2008), ka hona ho thata ho qolla karolo e hlakileng ea libaka tse ikhethang tsa boko le mefuta ea lisele ho buisanang le tlhekefetso ea Δ9-tetrahydrocannabinol (THC). Haufinyane, ho tlosoa hoa CB1 ho tloha D1+ Li-MSN li fumanoe li ama likarabo tsa boitšoaro ka tsela e nang le boinyenyefatso ho THC, ho kenyelletsoa le litlamorao tse senyehileng ho hypolocomotion ea THC, hypothermia, le analgesia (Monory et al., 2007). E ka ba ho khahlisang ho lekola ts'ebetso ea cannabinoid receptor ho D2+ Li-MSN ho tloha ha li-MSN tsena li bontša khatello ea maikutlo e telele ea nako e telele (eCB-LTD), e hlokang dopamine D2-receptor activation (Kreitzer le Malenka, 2007).

Li-receptor tsa glucocorticoid, Nr3c1, le eona e hlahisoa ka mokhoa o pharaletseng ho CNS le periphery. Secretion ea khatello ea maikutlo e bakoang ke khatello ea maikutlo e ka baka boitšoaro bo bobe bo ka kenyeletsang le ts'ebeliso e mpe ea lithethefatsi (Frank le al., 2011). Haholo-holo, ho senya tlhahiso ea glucocorticoid ho D1+ Li-MSN ka ho hlakola Nr3c1 li fokolitse tšusumetso eo litoeba tsena li li bontšang ho itšebelletsa koae, 'me sena se lumellana le data e fetileng moo Nr3c1 e ileng ea hlakolwa ho tsoa bokong bohle (Ambroggi et al., 2009). Lintlha tsena li tsamaisana le liphumano tse ling tse hlalositsoeng tlhahlobisong ena, li bonts'a karolo ea mantlha ea D1+ Li-MSN ha li sebelisana le litlamorao tse ngata tsa lithethefatsi tsa tlhekefetso.

Kamora nako, haufinyane re sa sitisitse ho saena ha BDNF ho li-MSN tse peli ka ho hlakola li-receptor tsa eona tsa TrkB ho khetha karolo e 'ngoe le e' ngoe ea MSN. Re hlokometse litla-morao tse fapaneng le boits'oaro bo khahlisang koae: ts'ebetso ea cocaine-e kenyellelitseng koae le ho kenngoa ha cocaine CPP ho matlafalitsoe kamora ho hlakoloa ha TrkB ho D.1+ Li-MSN, empa tsa emisoa ka mor'a ho tlosoa ho D2+ Li-MSN (Lobo et al., 2010). Ho khahlisang, ho tlosoa ha TrkB ho tloha D2+ Li-MSN li etsisa litlamorao tsa ho tlosoa ka ho felletseng ha TrkB ho tsoa ho NAc le pherekano ea ho supa ha BDNF ho tsoa ho VTA (Horger et al., 1999; Graham et al., 2007, 2009; Bahi et al., 2008; Crooks et al., 2010). Liphumano tsena li bonts'a lekhetlo la pele karolo e hlahelletseng ea sebapali sa 'mino se bonts'ang ho D2+ Li-MSN ha li buisana le litlamorao tsa lithethefatsi tsa tlhekefetso. Karolo e ka sehloohong ea D2+ Li-MSN ha li buisana ka litlamorao tsa BDNF litloaelong tse nang le boikoetliso ba koae, ha ho makatse ha ho nahanoa ka bobeli ba TrkB mRNA le protheine e ruisitsoe ho D2+ Li-MSN (Lobo et al., 2010; Baydyuk et al., 2011). Liphetoho tsa boits'oaro bo bonoang litali tsena li ne li tsamaisana le tšebetso e ntlafalitsoeng ea neuronal ho D2+ Li-MSN ho ea kokota ka khetho ea TrkB. Liphumano tsena li re khothalelitse ho sebelisa theknoloji ea optogenetic ho theha mosebetsi oa MSN ka mokhoa o ikhethileng moputsong oa koae (bona ka tlase).

Lintlha tsa Transaction ho D1 vs. D2 Li-MSN

Bopaki bo qobellang ka ho fetisisa bakeng sa karolo e matla ea D1+ Li-MSN tlhekefetsong ea lithethefatsi li tsoa ho lingoliloeng tse lekolang ho kenngoa ha limolek'hule tsa maqhubu a intracellular signaling. Joalokaha ho boletsoe kaholimo, tekanyetso e matla ea li-psychostimulants e susumetsa polelo ea IEG, ho kenyelletsa c-Fos, Zif268 (Egr1), le FosB haholo-holo ho D.1+ Li-MSN ho NAc le dStr (Robertson et al., 1991; Young le al., 1991; Berretta et al., 1992; Cenci et al., 1992; Moratalla et al., 1992; Bertran-Gonzalez et al., 2008). Ho kenella hona ho hloka hore ts'ebetso ea D e sebetse1 li-receptors, le boleng ba mofuta oa selefouno ea IEG ha li arabela cocaine e mpe haholo bo sa tsoa tiisoa ba sebelisa D1-GFP le D2Litoeba tsa mohatisi -GFPBertran-Gonzalez et al., 2008). Ho khahlisang, netefatso ea tlhahiso ea cocaine ea c-Fos haholo-holo ho D1-GFP ho pholletsa le striatum e kenyellelitsoe ntho e nyane ho D2-GFP MSNs feela ho dStr e netefalitsoe ho sebelisa paradigm e itšetlehileng ka maemo (litoeba li kentsoe sebakeng sa lipalesa ka ntle ho kharebe ea bona). Ho feta moo, thuto e fetileng e sebelisang in situ nyalatso ea litoeba e boetse e bonts'a ho kenella ha c-Fos ho D1+ le D2+ Li-MSN ho dStr, leha ho le joalo lithutong tsena tsa baemeli ba barupuli ba bonts'a palo e kholo ea D1+ c-Fos tse molemo li-neurons (Ferguson et al., 2006). Ho khahlisang, thuto ena e senola haholo tlhahiso ea c-Fos ho D2+ Li-MSN ka har'a dStr ka mor'a ho lahleheloa ke ERK1, e tsamaellanang le liphetho tsa rona tsa ntlafatso ea c-Fos e ntlafalitsoeng ho D2+ Li-MSN ka ho khetheha ka har'a khetla ea NAc ka mor'a ho senyeha ha lets'oao la BDNF le tsejoang ho ntlafatsa ts'ebetso ea ERK (Lobo et al., 2010). Leha ho le joalo, likarabo tse fapaneng tsa boitšoaro ba koae li ile tsa bonoa thutong ka 'ngoe, tse ka bonts'a ho kenella ha c-Fos ho D2+ Li-MSN ho dStr vs. NAc shell. Qetellong, lingoliloeng tse fetileng li sebelisa in situ hybridization / immunohistochemistry ho likhoto li bontšitse li-psychostimulants tse matla li ka hohela c-Fos ka mokhoa o ts'oanang ho li-MSN ka bobeli ha moriana o fanoa tikolohong ea lipalesa (Badiani et al., 1999; Uslaner et al., 2001a,b; Ferguson le Robinson, 2004) le taolo e sa fetoheng ea amphetamine ho tlalehoa hore e susumetsa c-Fos ho D2+ Li-MSN (Mattson et al., 2007). Liphetho tsena tse fapaneng e ka ba sesupo sa mekhoa ea liteko e sebelisitsoeng (in situ hybridization vs. GFP reporter litoeba) kapa e ka ba ka lebaka la mofuta oa liphoofolo o sebelisitsoeng joalo ka liteko tsa morao-rao tse sebelisitseng likhoto.

Haufinyane, bafuputsi ba hlahisitse mofuta oa "cocaine" o itšetlehileng ka methapo ea kutlo, 'me ba bonts'a hore li-neurons tsa c-Fos + li ruisitsoe ho D.1+ MSN gene, prodynorphin (Pdyn), empa e na le maemo a tlase a D2 Le A2A, ka bobeli D2+ Mefuta ea MSN (Guez-Barber et al., 2011), e fana ka maikutlo a hore li-neuron tsa c-Fos + tse hlahisitsoeng li na le D1+ Li-MSN. Ntle le moo, sehlopha sena se kile sa bonts'a hore li-c-Fos tse hlalosang li-MSN li bohlokoa molemong oa ts'usumetso e itšetlehileng ka maemo, kaha li-neurons tsena li felisa mokhoa ona oa boitšoaro (Koya et al., 2009). Le ha data e fetileng e bonts'itse hore ts'oaetso ea cocaine e itšetlehileng ka c-Fos e etsahala ho D1+ le D2+ Li-MSN ka likhoto, liphetho tsa morao-rao li lumellana le liphetho tsa ha ho tlosoa hoa c-Fos ka mokhoa o khethollang ho D1+ Li-MSN li blunts sensitization ea cocaine-e kenyellelitsoeng ho litoeba ho litoeba (Zhang et al., 2006). Ntle le moo, sehlopha sena se fumane hore ho tlosoa ha c-Fos ho D1+ Li-MSN li hlakisa liphetoho tsa mokokotlo oa dendritic hangata tse hlahisoang ke koae ho NAc, e bonts'a karolo ea c-Fos ho hanyetsanang liphetoho tsena tsa polasetiki ea synaptic. Kamora nako, sehlopha ha se a bona phetoho ho kenyeng k'hok'heine ea koae, empa ea fumana hore tahlehelo ea c-Fos ho D1+ Li-MSN li thibetse ho felisoa ha koae ea koae. Lintlha tse joalo li bonts'a karolo e matla ea phetoho ea c-Fos ho D1+ Li-MSN, leha ho le joalo, motho a ke ke a ahlola litlamorao ho boemo ba boits'oaro ka hore o buelloa ke efe kapa efe ea likarolo tse ling tsa 'mele tse hlalosang D tse hlalosang D1 mokamoli.

IEG e 'ngoe e ithutileng haholo lithutong tse peli tsa MSN ke FosB. Ho pepeseha ka matla k'hok'heine e hohola FosB ho D1+ Li-MSN (Berretta et al., 1992), athe ho pepeseha ho sa feleng ho hlohlelletsa ΔFosB, sehlahisoa se tsitsitseng sa mofuta oa FosB se hlahisoang ke ho hlahisa mefuta e meng hape (Hope et al., 1994; Nestler et al., 2001; Nestler, 2008), ho D1+ Li-MSN (Nye et al., 1995; Moratalla et al., 1996; Lee le al., 2006). Liphumano tse tšoanang li bonoa le lithethefatsi tse ling tse ngata tsa tlhekefetso hammoho le meputso ea tlhaho e kang lijo, thobalano le mabili a matha. Mohlala, ho tsamaea ka wheel wheel, e leng moputso oa tlhaho (Iversen, 1993; Belke, 1997; Lett et al., 2000), induces ea ΔFosB ho D1+ Li-MSN empa eseng D2+ Li-MSN (Werme et al., 2002). Ho fumana leseli le sebetsang mabapi le karolo ea ΔFosB ho li-MSN tse peli, sehlopha sa rona se hlahisitse mela ea NSE-tTa, e bitsoang 11A le 11B, e lebisang polelo ea transgene ho D1+ kapa D2+ Li-MSN, ka ho latellana (Chen le al., 1998; Kelz et al., 1999; Werme et al., 2002). Litoeba tsa Line 11A li harelane ka mola oa Tet-Op ΔFosB li bonts'a likarabo tse ngata ho litlamorao le ho khahlapetsoa hoa koae (cocaine)Kelz et al., 1999), e lumellanang le tlhahiso ea ΔFosB ho D1+ Li-MSN (Nye et al., 1995; Moratalla et al., 1996). Ho feta moo, litoeba tsena tse tšoanang li bonts'a moputso o eketsehileng oa morphine (o lekantsoe ke CPP) hammoho le morphine analgesia le ntlafatso ea mamello ea morphine, athe litoeba tsa 11B Tet-Op ΔFosB ha li bontše phetoho moputsong oa morphine. Tlhatlhobo e feteletseng ea mohanyetsi ea matla oa ΔFosB e hlahisa litlamorao tse fapaneng le tse bonoang ke ΔFosB, leha mohlala ona oa mouse o sa khetholle D1 vs. D2 Li-MSN (Peakman et al., 2003). Ka kopanelo, lintlha tsena li ts'ehetsa karolo ea ho kenya ΔFosB ho D1+ Li-MSN e le sebapali sa bohlokoa sa limolek'hule meahong e khotsofatsang ea lithethefatsi tsa tlhekefetso (Zachariou et al., 2006). Ntho ena e boetse e bonoa mekhoeng e meng ea moputso, haholo lebelo la mabili: 11A Tet-Op ΔFosB litoeba li bonts'a mokhoa o fetisisang oa maqhubu, athe 11B Tet-Op ΔFosB litoeba li fokotsehile ha li tsamaea ka mabelo (Werme et al., 2002). Ho fumana hore ΔFosB ho kenyelletsa D1 Li-MSN li khothaletsa moputso ho tsamaisana le liphumano tsa morao-rao tsa hore mofuta o joalo oa khetho ea sele le ona o khothaletsa likarabo tsa ho sebetsana ka katleho le khatello ea maikutlo e sa feleng (Vialou et al., 2010). Kamora nako e telele, "cocaine e sa foleng" ea D1+ Li-MSN li bontšitsoe hore li tsamaisana le keketseho e telele ea nako e telele ea methapo ea methapo ea mokokotlo ea dendritic (Lee le al., 2006) mme haufinyane ΔFosB ho NAc e bonts'itsoe e hlokahala ebile e lekane ha ho tsamaisana le methapo ea methapo ea methapo tikolohong ena ea boko (Maze et al., 2010). Lintlha tse joalo li tšehetsa karolo ea ΔFosB ho D1+ Li-MSN ha li buisana ka likarolo tse khahlisang tsa lithethefatsi tsa tlhekefetso le meputso ea tlhaho hammoho le liphetoho tse tsamaellanang le tsona. Lintlha li boetse li fana ka tlhahiso ea hore induction ea ΔFosB ho D2+ Li-MSN li fana ka liphetho tse mpe ho susumetso e ntle. Ho tloha ka ΔFosB kenyelletso ka D2+ Li-MSN li bonoa ha li araba khatello ea maikutlo e sa feleng le ho pepeseha ha lithethefatsi tsa antipsychotic (Hiroi le Graybiel, 1996; Perrotti et al., 2004), lithuto tse ling tsa liketso tsa morao-rao lia hlokahala.

Limolek'hule tse Ling Tse Ikhethileng tsa D1 vs. D2 Li-MSN

Molek'hule e le 'ngoe e bonts'ang hantle e ithutoang hantle ho li-MSN tse peli maemong a ts'ebeliso e mpe ea lithethefatsi ke kinase ea protheine, ERK (extracellular sign amanang kinase). Phihlello e mpe kapa e sa foleng ea cocaine induces phosphorylated ERK (pERK), sebopeho se sebetsang sa protheine, ho NAc le dStr ho D1+ Li-MSN li sebelisa D1-GFP le D2-GFP BAC transgenic mokoeteliBertran-Gonzalez et al., 2008) mme karabelo ena e kopantsoe ka D1 receptors (Valjent et al., 2000; Lu et al., 2006). Sehlopha sena se boetse se bonts'itse hore pMSK-1 (phospho-MAP le khatello ea maikutlo e entsoe kinase-1) le histone H3, lipolao ka bobeli tsa ho saena hoa PERK, li kenelletse ka matla pERK e nang le D.1+ Li-MSN ka mor'a ho pepesetsoa koae ka ho feteletseng le ka boinyenyefatso li eketsehile kamora ho ts'oara koae (Bertran-Gonzalez et al., 2008). pERK e boetse e ts'oaroa ke karabelo ho morphine e sa foleng, haholo, pERK e qalile ka mokhoa o matla ho D1+ Li-MSN 'me ka mokhoa o itekanetseng o thehiloe ho D2+ Li-MSN ka har'a khetla ea NAc ka mor'a ho ikhula ho araba kamano e ikhethileng e amanang le morphine (Borgkvist et al., 2008). Karolo e sebetsang ea pERK bokhobeng ba lithethefatsi e ntse e tlameha ho tsejoa. Phekolo ea pharmacological e nang le inhibitors ea ERK e bontšitsoe hore e fokotsa moputso oa koae, leha ho le joalo, ho kokota ha moputso oa ERK1 potentiates potocaates cocaine, ho fana ka maikutlo a hore pele li-ERK inhibitors li ka ama ERK2. Haufinyane tjena, re bonts'itse ts'ebetso ea optogenetic ea D1+ Li-MSN ho NAc, e eketsang likarabo tse khotsofatsang tsa phoofolo ho koae, e ka fokotsa pERK1 ka bobeli le pERK2. Boithuto ba nako e tlang bo theolang polelo ea ERK ka mokhoa o ikhethileng oa sele e hlokahala ho sebetsana ka botlalo le karolo e sebetsang ea ERK ea ho supa li-MSN tse peli tlhekefetsong ea lithethefatsi.

DARPP-32 ke molek'hule e 'ngoe e tšoaeang e ithutoang haholo ho arabela lithethefatsi tsa tlhekefetso. Hoa tsebahala hore li-psychostimulants tse mpe li lebisa ho PKA phosphorylation ea DARPP-32 ho threonine 34 (T34), e e etsa hore e be sebopeho se nang le matla sa protheine phosphatase 1 (PP-1), e laolang boemo ba phosphorylation ba liprotheine tse ngata tse sebetsang. lintlha tsa sengoloa, li-ionotropic receptors, le liteishene tsa ion (Greengard et al., 1999). Leha ho le joalo, ho fihlela haufinyane tjena, ho ne ho sa hlaka hore na ke subtype ea MSN e sebelisang phetoho ena ea biochemical. Greengard et al. (1999) hlahisa meetso ea khokahano ea "BAC transgenic" e lumellang tlhahlobo ea phosphorylation ea DARPP-32 ho D1+ kapa D2+ Li-MSN ka ho hlahisa mefuta e mengotsoeng ea DARPP-32 u sebelisa D1 kapa D2 Li-BAC tse lumellang immunoprecipitation ea DARPP-32 ho tsoa ho subtype ka 'ngoe ea MSN. Lithuto tsena li bonts'itse hore kalafo ea cocaine e hlobaetsang e eketsa phosphorylation ea T34 ho D1+ MSNs le induces phosphorylation ea threonine 75 (T75) ke Cdk5, e thibelang ho saena ha PKA, ka boikhethelo ho D2+ Li-MSN (Bateup et al., 2008). Kamora nako sehlopha sena se bonts'itse hore ho tlosoa ha DARPP-32 moqhekeng ka mong oa MSN o sebelisa D1-Cre le D2Likhoto tsa transgenic tsa Bre li hlahisa sephetho se fapaneng sa ts'ebetso ea koae e khothalletsoang ke koae.Bateup et al., 2010). Ho lahleheloa ke DARPP-32 ho tloha D1+ Li-MSN li fokolisitse litlamorao tsa cocaine, e lekanang le tlhaiso-leseling ea nakong e fetileng e neng e hlahloba kakaretso ea DARPP-32Fienberg et al., 1998), athe tahlehelo ea DARPP-32 ho tloha D2+ Li-MSN li ntlafalitse likarabo tsa koae. Lintlha tse joalo li fana ka bopaki bo hlakileng ba likarolo tse fapaneng tsa DARPP-32 ho li-MSN tse peli ho arabela lithethefatsi tsa tlhekefetso mme li bonts'a bohlokoa ba mekhoa e ikhethang ea mofuta oa sele ho utloisisa ka botlalo phano ea mefuta ena e 'meli ea li-neuronal tšebelisong ea lithethefatsi.

Mosebetsi oa Modulating oa D1 kapa D2 Li-MSN

Ho feto-fetoha ka kotloloho mosebetsi oa li-subtypes tse peli tsa MSN haufinyane ho fane ka leseli la lipale mabapi le karolo ea molek'hule le tšebetso ea D.1 le D2 Li-MSN ke temallo. Re sebelisitse lisebelisoa tsa optogenetic hammoho le seteraete se nang le maemo (e leng, se itšetlehileng ka mofuta oa) oa adeno-a amanang le adeno ("AAV)" se neng se hlahisa mocha oa "blue" activated cation channel, chrXododin-2 (ChR2). Re kentse vector, kapa taolo, ho NAc ea D1-Cre kapa D2-Cre BAC transgenic mice ebe e tsosa sebaka se kentsoeng ka leseli le bolou ho khetha ka hloko D1+ vs. D2+ Li-MSN maemong a CPP a cocaine. Re fumane tšebetso eo ea D1+ Li-MSN li khona ho kenyelletsa CPP ea koae, empa ts'ebetso ea D2+ Li-MSN li thibela tšebetso ena (Lobo et al., 2010). Joalokaha ho hlokometsoe pejana, re hlokometse litlamorao tse tšoanang tsa boitšoaro ha TrkB e tlosoa ka mokhoa o ikhethileng ho tsoa ho li-subtypes tsena tsa MSN: ts'ebetso ea CPP ea cocaine le ts'ebetso ea locomotor kamora ho tlosoa ha TrkB ho D1+ Li-MSN, le phokotso ea cocaine CPP le ts'ebetso ea locomotor kamora ho tlosoa ha TrkB ho D2+ Li-MSN. Ketso e ka 'nang ea tloaeleha ea TrkB ea ho kokota le ho hlohlelletsoa ha optogenetic ho D2+ Li-MSN ke mosebetsi oa bona o eketsehileng, kaha ho tlosoa ha TrkB liseleng tsena ho eketsa thabo ea bona ea motlakase. Joalokaha ho boletsoe pejana, re fumane le phokotso e matla ea pERK kamora ho tlosoa ha TrkB ho D1+ Li-MSN. PERK ke sepheo se tsebahalang sa ho theoha ha letšoao la BDNF, ka hona, litlamorao tsa boitšoaro bo boletsoeng kamora ho tlosoa ha TrkB ho D1+ Li-MSN le ts'ebetso ea optogenetic ea ts'ebetso ea lisele tsena e kanna ea ba ka lebaka la liphetho tse fetohang mosebetsing oa pERK. Leha ho le joalo, ho hlokahala mosebetsi oa nako e tlang ho fumana lintlha tse hlakileng, tse arolelanoang tsa limolek'hule tse laolang litlamorao tsa boits'oaro tse bonoang kamora ho sitisoa hoa ho saena hoa BDNF le taolo ea optogenetic ea li-subtypes tsena tse peli tsa neuronal.

Lihlopha tse ling li sebelisitse lisebelisoa tse fapaneng ho fetolela tšebetso ea li-MSN tse peli mehlaleng ea tlhekefetso ea lithethefatsi. Hikida et al. (2010) sebelisa veA ea AAV ho hlahisa tetracycline-replication transaction factor (tTa) o sebelisa ntho P (a D1+ MSN gene) kapa enkephalin (a D2+ Barekisi ba mofuta oa MSN). Lierekisi tsena li ile tsa kenngoa ka har'a NAc ea litoeba, moo tetanus toxin light chain (TN) - chefo ea baktheria e kholisang protheine e amanang le li-synaptic, VAMP2 - e ne e laoloa ke ts'ehetso ea phetiso ea tetracycline ho e ngoe le e ngoe. Tlhokomelo ea MSN. E lumellana le mokhoa oa rona oa optogenetic, datha tsena li bonts'a karolo ea D1+ Ts'ebetso ea MSN ho ntlafatsa cocaine CPP le mosebetsi oa locomotor oa koae, kaha e felisa phetiso ea synaptic ho D1+ Li-MSN li fokolisitse litlamorao ka bobeli ba boitšoaro. Ho fapana le lithuto tsa optogenetic, bangoli ha baa ka ba fumana liphetoho lipapaling tsa koae ka mor'a ho felisa phetiso ea synaptic ho D.2+ Li-MSN, empa li hlokometse tšebetso e fokotsehileng ea koae ka lebaka la liphatlalatso tse peli tsa pele tsa koae. Ho khahlisang, sehlopha sena se bonts'itse ts'ebetso ea D2+ Li-MSN li nkile karolo e tebileng ho hanana le boits'oaro bo fapaneng.

Joalokaha ho boletsoe pejana, Ferguson et al. (2011) sebelisa li-vepes tsa herpes simplex virus (HSV) ho hlalosa GPCR ea enjine (a Gi / o-motsoana oa batho oa mokokotlo oa M4 moetsi oa li-receptor o etsoa feela ke sethethefatsi sa moqapi, hM4D) e hlahisoang ke motsoako o mong oa meriana o sebelisang k'homphieutha ea ts'ephalin le dynorphin ho khetha D1+ kapa D2+ Li -MSN ho dStr. Bangoli ba bonts'a hore ho senya nako e telele ho ferekanya D2+ Ts'ebetso ea MSN ho dStr e nolofalitse maikutlo a amphetamine, athe ho fokotseha hoa thabo ea D1+ Li-MSN li sitisitse ho phehella ha maikutlo a amphetamine. Qetellong, ho felisoa D2+ Li-MSN ho NAc ka nako ea batho ba baholo ba sebelisang diptheria toxin receptor li matlafatsa phello e thabisang ea amphetamine (Durieux et al., 2009). Lintlha tse joalo li lumellana le liphetho tsa rona tsa optogenetic, 'me hammoho li sebetsa likarolo tse fapaneng tsa D1+ vs. D2+ Li-MSN taolong ea lithethefatsi, li na le D1+ Li-MSN li khothaletsa karabelo ea moputso le ho khahla likarabo ho li-psychostimulants le D2+ Li-MSN li nyenyefatsa boitšoaro bona.

Litaelo tsa nakong e tlang

Tšimo e hatetse pele haholo ho utloisisa karolo e khethiloeng ea D1+ le D2+ MSN subtypes ho NAc le dStr ho arola litlamorao tsa lithethefatsi tsa tlhekefetso. Haholo-holo, lisebelisoa tse sa tsoa etsoa tse nolofalletsang ho qhekella ho khethehileng ha mefuta ena ea lisele ho bapala karolo ea bohlokoa ho fumana boholo ba tlhaiso-leseling ena. Mehato e latelang ke efe? Kaha liphetoho tse ka sehlohlolong tsa limolek'hule tsa lithethefatsi ha li ts'oanehe, empa li matla haholo, ho bohlokoa ho nts'etsapele bokhoni ba ho sebelisa hampe limolek'hule tse bontšang thahasello ho D.1+ vs. D2+ Li-MSN ka mokhoa o nepahetseng oa nakoana. Lisebelisoa tsa li-DREADD le lisebelisoa tsa optogenetic li ka thusa ka mokhoa ona oa ho qhekella nakong ena. Li-ligands tsa DREADD li ka tsamaisoa ka linako tse fapaneng ho pholletsa le litekanyetso tsa boitšoaro ba lithethefatsi ho etsa karolo ea khetho ea ho saena li-receptor ho li-MSN tse peli mefuteng ea lithethefatsi. Lisebelisoa tsa optogenetic ka ho khetheha li fana ka mokhoa o matla haholo oa ho laola ka nakoana ts'ebetso ea neuronal empa G-protein-coupled receptor signaling e sebelisang OptoXRs (Airan et al., 2009), glutamatergic signing (Volgraf et al., 2006; Numano et al., 2009), GABAergic signaling, esita le limolek'hule tse ling tsa maqhubu a hlakileng (Wu et al., 2009; Hahn le Kuhlman, 2010). Qetellong, ho kanna ha khonahala ho holisa bokhoni bona ho tsamaiso ea optogenetic ea tšebetso ea mongolo. Ka mokhoa o ts'oanang, lisebelisoa tsa optogenetic li etsa hore ho be le nako ea pele ea ho ithuta tšusumetso ea lisebelisoa tse ikhethileng ho striatum le ho bona hore na liphallelo tse joalo li ka baka mekhoa e khethiloeng ho D.1+ vs. D2+ Li-MSN (Higley le Sabatini, 2010). Bokhoni ba ho laola thepa e joalo ea lets'oao le ea limolek'hule tse nang le tharollo e kholo ea nakoana e tla lumella mehato e meholo ho etsoa kutloisisong e batsi ea li-subtypes tse peli tsa MSN, le li-subtypes tse ling tsa cell ho NAc le dStr, ka ho nka nako ea nako le likarolo tse fapaneng tsa lithethefatsi temallo.

Tlhōlisano ea Tlhaloso

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.

References

Airan, RD, Thompson, KR, Fenno, LE, Bernstein, H., le Deisseroth, K. (2009). Ho nepahala ha nakoana taolong ea vivo ea lets'oao la intracellular. Nature 458, 1025-1029.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Albin, RL, Monyane, AB, le Penney, JB (1989). Anatomy e sebetsang ea mathata a basal ganglia. Trends Neurosci. 12, 366-375.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Alexander, GE, Delong, MR, le Strick, PL (1986). Mokhatlo o lumellanang oa lipotoloho tse arohaneng tse hokahanyang basal ganglia le cortex. Annu. Moruti Neurosci. 9, 357-381.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Ambroggi, F., Turiault, M., Milet, A., Deroche-Gamonet, V., Parnaudeau, S., Balado, E., Barik, J., Van Der Veen, R., Maroteaux, G., Lemberger , T., Schutz, G., Lazar, M., Marinelli, M., Piazza, PV, le Tronche, F. (2009). Khatello ea kelello le ho lemalla: glucocorticoid receptor ho dopaminocepts neurons e nolofalletsa motho ea batlang koae. Nat. Neurosci. 12, 247-249.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Bachtell, RK, Choi, KH, Simmons, DL, Falcon, E., Monteggia, LM, Neve, RL, le Self, DW (2008). Karolo ea polelo ea GluR1 ho li-nucleus e bokella li-neurons ho sensitization ea cocaine le boitšoaro bo batlang koae. EUR. J. Neurosci. 27, 2229-2240.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Bachtell, RK, le Self, DW (2008). Ho pepesetsoa ha koae ho hlahisang liphetoho tsa nakoana ho li-nucleus accumbens AMPA receptor-mediated boitšoaro. J. Neurosci. 28, 12808-12814.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Bachtell, RK, le Self, DW (2009). Litlamorao tsa adenosine A2A receptor ho susumetsa boitšoaro bo batlang cocaine ho likhoto. Psychopharmacology (Berl.) 206, 469-478.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Badiani, A., Oates, MM, Letsatsi, HE, Watson, SJ, Akil, H., le Robinson, TE (1999). Phetoho ea tikoloho ea polelo ea amphetamine-induction c-fos ho D1 le D2 striatal neurons. Behav. Resin ea Boko. 103, 203-209.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Bahi, A., Boyer, F., Chandrasekar, V., le Dreyer, JL (2008). Karolo ea ho bokella li-BDNF le TrkB ho sensorization ea cocaine e kenyellelitseng k'hok'heine, khetho ea sebaka se ikhethileng, le ho khutlisetsoa likhotong. Psychopharmacology (Berl.) 199, 169-182.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Bateup, HS, Santini, E., Shen, W., Birnbaum, S., Valjent, E., Surmeier, DJ, Fisone, G., Nestler, EJ, le Greengard, P. (2010). Likarolo tse fapaneng tsa "li-neurons" tsa "spiny" tse fapaneng li laola ka ho fapana mekhoa ea boits'oaro bo tsamaeang ka maoto. Proc. Natl. Acad. Sci. usa 107, 14845-14850.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Bateup, HS, Svenningsson, P., Kuroiwa, M., Gong, S., Nishi, A., Heintz, N., le Greengard, P. (2008). Tekanyetso e khethehileng ea mofuta oa selefouno ea phosphorylation ea DARPP-32 ka li-psychostimulant le li-antipsychotic drug. Nat. Neurosci. 11, 932-939.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Baydyuk, M., Nguyen, MT, le Xu, B. (2011). Ho fokotseha ho sa feleng ha letšoao la TrkB ho lebisa ho khethollo ea morao ea ho qala ha nigrostriatal dopaminergic degeneration. Exp. Neurol. 228, 118-125.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Belke, TW (1997). Ho matha le ho arabela ho matlafatsoa ke monyetla oa ho matha: phello ea nako ea ho tiisa. J. Ntlo. Anal. Behav. 67, 337-351.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Bernard, V., Normand, E., le Bloch, B. (1992). Tšoaetso ea phenotypical ea li-neurons tsa "striatal neurons" tse hlalosang mefuta ea "mino" ea "receptor" ea "mescarinic". J. Neurosci. 12, 3591-3600.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Berretta, S., Robertson, HA, le Graybiel, AM (1992). Li-dopamine le li-agonists tsa glutamate li hlohlelletsa polelo e tobileng ea neuron ea protheine e kang ea Fos ho striatum. J. Neurophysiol. 68, 767-777.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Bertran-Gonzalez, J., Bosch, C., Maroteaux, M., Matamales, M., Herve, D., Valjent, E., le Girault, JA (2008). Mekhoa e hanyetsang ea ts'ebetso e tšoaeang ts'ebetso ea dopamine D1 le D2 receptor-e bontšang striatal neurons ha e arabela cocaine le haloperidol. J. Neurosci. 28, 5671-5685.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Beurrier, C., le Malenka, RC (2002). Inhibition e ntlafalitsoeng ea phetiso ea synaptic ka dopamine ka har'a li-nucleus tsa "nucleus" nakong ea maikutlo a boitšoaro ho cocaine. J. Neurosci. 22, 5817-5822.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Beutler, LR, Wanat, MJ, Quintana, A., Sanz, E., Bamford, NS, Zweifel, LS, le Palmiter, RD (2011). Ts'ebetso e lekantsoeng ea NMDA receptor ho dopamine D1 receptor (D1R) - le D2R-e hlalosang li-spiny neurons tse bohareng li hlokahala bakeng sa sensorization ea amphetamine. Proc. Natl. Acad. Sci. usa 108, 4206-4211.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Borgkvist, A., Valjent, E., Sstrong, E., Herve, D., Girault, JA, le Fisone, G. (2008). Ho lieha, moelelo- le dopamine D1-ts'ebetso e itšetlehileng ka ts'ebeliso ea ERK ho litoeba tsa morphine-sensitised. Neuropharmacology 55, 230-237.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Caine, SB, Negus, SS, Mello, NK, Patel, S., Bristow, L., Kulagowski, J., Vallone, D., Saiardi, A., le Borrelli, E. (2002). Boikarabello ba li-receptor tsa dopamine D2-cocaine ho itlhokofatsa: lithuto le litoeba tsa D2 receptor mutant le nova ea D2 receptor antagonists. J. Neurosci. 22, 2977-2988.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Caine, SB, Thomsen, M., Gabriel, KI, Berkowitz, JS, Khauta, LH, Koob, GF, Tonegawa, S., Zhang, J., le Xu, M. (2007). Ho haelloa ke ts'ebetso ea koae ho dopamine D1 li-receptor. J. Neurosci. 27, 13140-13150.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Cardin, JA, Carlen, M., Meletis, K., Knoblich, U., Zhang, F., Deisseroth, K., Tsai, LH, le Moore, CI (2010). Ts'usumetso e tsitsitseng ea optogenetic le ho rekota ha li-neuron ho vivo li sebelisa polelo e khethehileng ea selefouno ea Channelrhodopsin-2. Nat. Protoc. 5, 247-254.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Cenci, MA, Campbell, K., Wictorin, K., le Bjorklund, A. (1992). Striatal c-fos induction ka koae kapa apomorphine e etsahala ka mokhoa o ikhethileng ho li-neurons tse hlahisoang ho fihla ho nigra e kholo ho rat. EUR. J. Neurosci. 4, 376-380.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Chausmer, AL, Elmer, GI, Rubinstein, M., Low, MJ, Grandy, DK, le Katz, JL (2002). Ketsahalo ea locomotor e hlahisoang ke cocaine le khethollo ea koae ho dopamine D2 receptor mutant mice. Psychopharmacology (Berl.) 163, 54-61.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Chen, J., Kelz, MB, Zeng, G., Sakai, N., Steffen, C., Shockett, PE, Picciotto, MR, Duman, RS, le Nestler, EJ (1998). Liphoofolo tsa Transgenic tse nang le polelo e sa bonahaleng e lebisitsoeng ho mofuta oa bokong. Mol. Pharmacol. 54, 495-503.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Conrad, KL, Tseng, KY, Uejima, JL, Reimers, JM, Heng, LJ, Shaham, Y., Marinelli, M., le Wolf, ME (2008). Ho hlophisoa ha li-accumbens GluR2-ntseng e haelloa ke li-AMPA li-mediates incubation ea takatso ea koae. Nature 454, 118-121.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Crawford, CA, Drago, J., Watson, JB, le Levine, MS (1997). Liphello tsa kalafo e pheta-phetoang ea amphetamine mosebetsing oa locomotor oa "dopamine D1A" defence mouse. Neuroreport 8, 2523-2527.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Crooks, KR, Kleven, DT, Rodriguiz, RM, Wetsel, WC, le Mcnamara, JO (2010). Ho tšoaea TrkB hoa hlokahala bakeng sa ho susumetsa boits'oaro le sebaka se ikhethileng se khetholloang ke ente e le 'ngoe ea koae. Neuropharmacology 58, 1067-1077.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Cunningham, CL, Howard, MA, Gill, SJ, Rubinstein, M., Low, MJ, le Grandy, DK (2000). Khetho ea sebaka sa maemo a leholimo ea feberu e fokotsehile ho litoeba tsa deptamine D2. Pharmacol. Likokoana-hloko. Behav. 67, 693-699.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Deroche-Gamonet, V., Sillaber, I., Aouizerate, B., Izawa, R., Jaber, M., Ghozland, S., Kellendonk, C., Le Moal, M., Spanagel, R., Schutz, G., Tronche, F., le Piazza, PV (2003). Glucocorticoid receptor e le sepheo se ka bang teng sa ho fokotsa ts'ebeliso e mpe ea koae. J. Neurosci. 23, 4785-4790.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Dietz, DM, Dietz, KC, Nestler, EJ, le Russo, SJ (2009). Lisebelisoa tsa limolek'hule tsa polasetiki ea psychostimulant. Pharmacopsychiatry 42 (Suppl. 1), S69-S78.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Drago, J., Gerfen, CR, Westphal, H., le Steiner, H. (1996). D1 dopamine receptor-defence mouse: taelo ea cocaine e kenyellelitsoeng ho liphatsa tsa lefutso tsa kapele-pele le tlhahiso ea P ho striatum. Khopolo-taba 74, 813-823.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Durieux, PF, Bearzatto, B., Guiducci, S., Buch, T., Waisman, A., Zoli, M., Schiffmann, SN, le De Kerchove D'Exaerde, A. (2009). D2R striatopallidal neurons inhibit bobeli mekhoa ea locomotor le litheko tsa lithethefatsi. Nat. Neurosci. 12, 393-395.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

El-Ghundi, M., George, SR, Drago, J., Fletcher, PJ, Fan, T., Nguyen, T., Liu, C., Sibley, DR, Westphal, H., le O'Dowd, BF (1998). Tšitiso ea tšebeliso ea genop ea DopNUMX ea dopamine e bontša mokhoa o batloang ke joala. EUR. J. Pharmacol. 353, 149-158.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Elmer, GI, Pieper, JO, Rubinstein, M., Low, MJ, Grandy, DK, le Wise, RA (2002). Ho hloleha ha morphine e kenang kahare ho sebetsa e le mochini o matlafatsang oa litheko tsa dopamine D2 receptor-Out. J. Neurosci. 22, RC224.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Ferguson, SM, Eskenazi, D., Ishikawa, M., Wanat, MJ, Phillips, PE, Dong, Y., Roth, BL, le Neumaier, JF (2011). Tšitiso ea nakoana ea neuronal e senola likarolo tse hanyetsanang tsa litsela tse sa tobang le tse tobileng tsa maikutlo. Nat. Neurosci. 14, 22-24.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Ferguson, SM, Fasano, S., Yang, P., Brambilla, R., le Robinson, TE (2006). Knockout ea ERK1 e ntlafatsa mokhoa o potlakileng oa tšebeliso ea koae le boits'oaro. Neuropsychopharmacology 31, 2660-2668.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Ferguson, SM, le Robinson, TE (2004). Amphetamine-evoke gene expression in striatopallidal neurons: regulation by corticostriatal afferents and the ERK / MAPK signaling Cascade. J. Neurochem. 91, 337-348.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Fienberg, AA, Hiroi, N., Mermelstein, PG, Sefela, W., Snyder, GL, Nishi, A., Cheramy, A., O'Callaghan, JP, Miller, DB, Cole, DG, Corbett, R. , Haile, CN, Cooper, DC, Onn, SP, Mohau, AA, Ouimet, CC, White, FJ, Hyman, SE, Surmeier, DJ, Girault, J., Nestler, EJ, le Greengard, P. (1998) . DARPP-32: molaoli oa katleho ea dopaminergic neurotransuction. Science 281, 838-842.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Filip, M., Frankowska, M., Zaniewska, M., Przegalinski, E., Muller, CE, Agnati, L., Franco, R., Roberts, DC, le Fuxe, K. (2006). Ho kenella ha adenosine A2A le dopamine receptors ho locomotor le litlamorao tse khahlisang tsa koae. Resin ea Boko. 1077, 67-80.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Frank, MG, Watkins, LR, le Maier, SF (2011). Ho sithabela ha khatello ea maikutlo le glucocorticoid tse bakang karohano ea khatello ea maikutlo: mefuta e ka bakang khatello ea maikutlo e bakang khatello ea maikutlo litlamorao tsa tlhekefetso. Brain Behav. Immun. 25, S21-S28.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Gerfen, CR (1984). The neostriatal mosaic: compartmentalization of corticostriatal input le striatonigral sistimi e hlahisang. Nature 311, 461-464.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Gerfen, CR (1992). Mokhoa oa kahare oa mahlo: Likarolo tse ngata tsa mokhatlo o hlophisitsoeng ka har'a basal ganglia. Annu. Moruti Neurosci. 15, 285-320.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Gerfen, CR, Engber, TM, Mahan, LC, Susel, Z., Chase, TN, Monsma, FJ Jr., le Sibley, DR (1990). D1 le D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science 250, 1429-1432.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Gerfen, CR, le Surmeier, DJ (2011). Modulation ea li-system tsa striatal proion ka dopamine. Annu. Moruti Neurosci. 34, 441-466.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Gerfen, CR, le Monyane, WS III. (1988). Tsamaiso ea li-neuron tsa "striatonigral" le "striatopallidal peptidergic neurons" ka bobeli ke patch le matrix compartments: e situ hybridization histochemistry and fluorescent retrograde track triding. Resin ea Boko. 460, 161-167.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Gong, S., Doughty, M., Harbaugh, CR, Cummins, A., Hatten, ME, Heintz, N., le Gerfen, CR (2007). Targeting Cre recombinase ho palo e ikhethileng ea li-neuron tse nang le libaktheria tsa maiketsetso tsa chromosome. J. Neurosci. 27, 9817-9823.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Gong, S., Zheng, C., Doughty, ML, Losos, K., Didkovsky, N., Schambra, UB, Nowak, NJ, Joyner, A., Leblanc, G., Hatten, ME, le Heintz, N . (2003). Polelo ea mofuta oa liphatsa tsa tsamaiso ea methapo e bohareng e thehiloeng ho li-chromosome tsa baktheria. Nature 425, 917-925.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Graham, DL, Edward, S., Bachtell, RK, Dileone, RJ, Rios, M., le Self, DW (2007). Ts'ebetso ea DDBic BDNF ho li-nucleus tse bokellanang ka tšebeliso ea koae e eketsa ho itaola le ho khutlela morao. Nat. Neurosci. 10, 1029-1037.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Graham, DL, Krishnan, V., Larson, EB, Graham, A., Edward, S., Bachtell, RK, Simmons, D., Gent, LM, Berton, O., Bolanos, CA, Dileone, RJ, Parada , LF, Nestler, EJ, le Self, DW (2009). Tropomyosin e amanang le kinase B tsamaisong ea mesolimbic dopamine: litlamorao tse ikhethang tikolohong ea moputso oa koae. Biol. Psychiatry 65, 696-701.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Graybiel, AM (2000). The basal ganglia. Curr. Biol. 10, R509-R511.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Greengard, P., Allen, PB, le Nairn, AC (1999). Ntle le recopor ea dopamine: Cascade ea DARPP-32 / protheine ea phosphatase-1. Neuron 23, 435-447.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Guez-Barber, D., Fanous, S., Golden, SA, Schrama, R., Koya, E., Stern, AL, Bossert, JM, Harvey, BK, Picciotto, MR, le Tshepo, BT (2011). FACS e khetholla molao o ikhethang oa "cocaine-ikiwa" oa "gene" ka ho khetheha. J. Neurosci. 31, 4251-4259.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Hahn, KM, le Kuhlman, B. (2010). O ntšoare ka thata LOV. Nat. Mekhoa 7, 595-597.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Heiman, M., Schaefer, A., Gong, S., Peterson, JD, Letsatsi, M., Ramsey, KE, Suarez-Farinas, M., Schwarz, C., Stephan, DA, Surmeier, DJ, Greengard, P., le Heintz, N. (2008). Mokhoa oa ho fetolela profiling bakeng sa sebopeho sa limolek'hule tsa mefuta ea lisele tsa CNS. Cell 135, 738-748.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Heusner, CL, Beutler, LR, Matlo, CR, le Palmiter, RD (2008). Ho tlosoa ha GAD67 ho dopamine receptor-1 e hlahisang lisele tse bakang khaello e khethehileng ea koloi. Genese 46, 357-367.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Heusner, CL, le Palmiter, RD (2005). Pontšo ea li-receptor tsa NMDA tse feto-fetohang ho dopamine D1 receptor e nang le lisele li thibela sensitization ea cocaine. J. Neurosci. 25, 6651-6657.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Higley, MJ, le Sabatini, BL (2010). Tekanyetso ea tlholisano ea li-synaptic Ca2 + protocol ka D2 dopamine le A2A adenosine receptors. Nat. Neurosci. 13, 958-966.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Hikida, T., Kimura, K., Wada, N., Fun fan, K., le Nakanishi, S. (2010). Karolo e arohaneng ea phetiso ea synaptic ka kotloloho ka kotloloho le ka kotloloho litsela tsa ho putsa le boitšoaro bo bobe. Neuron 66, 896-907.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Hiroi, N., le Graybiel, AM (1996). Litlhare tsa kalafo tsa "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "Ancypical" "kalafo" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "" "T'asali" "" "" "" "" "" "" "" "" "" "" "" "" "Essipical" J. Comp. Neurol. 374, 70-83.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Tšepo, BT, Nye, HE, Kelz, MB, Self, DW, Iadarola, MJ, Nakabeppu, Y., Duman, RS, le Nestler, EJ (1994). Tlhahiso ea motsoako oa AP-1 oa nako e telele o qapiloeng ke liprotheine tse kang Fos ka bokong ka cocaine e sa feleng le kalafo tse ling tse sa foleng. Neuron 13, 1235-1244.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Horger, BA, Iyasere, CA, Berhow, MT, Messer, CJ, Nestler, EJ, le Taylor, JR (1999). Ntlafatso ea ts'ebetso ea locomotor le moputso o nang le boemo ho cocaine ke motsoako oa boko o tsoang ho bokong. J. Neurosci. 19, 4110-4122.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Ince, E., Ciliax, BJ, le Levey, AI (1997). Polelo e fapaneng ea D1 le D2 dopamine le m4 muscarinic acetylcholine receptor protheine ho li-neurons tse tsebahalang tsa striatonigral. Synapse 27, 357-366.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Iversen, IH (1993). Mekhoa ea ho theha kemiso e nang le mabili a tsamaeang joalo ka tokisetso ea lithebe. J. Ntlo. Anal. Behav. 60, 219-238.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Jeon, J., Dencker, D., Wortwein, G., Woldbye, DP, Cui, Y., Davis, AA, Levey, AI, Schutz, G., Sager, TN, Mork, A., Li, C. , Deng, CX, Fink-Jensen, A., le Wess, J. (2010). Ho kenella ka tlase ho li-receptor tsa neuronal M4 muscarinic acetylcholine ho bapala karolo ea bohlokoa ho fetoleng boits'oaro bo its'epahallang ke dopamine. J. Neurosci. 30, 2396-2405.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Kalivas, PW (2009). The glutamate homeostasis hypothesis ea ho lemalla. Nat. Rev. Neurosci. 10, 561-572.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Kelz, MB, Chen, J., Carlezon, WA Jr., Whisler, K., Gilden, L., Beckmann, AM, Steffen, C., Zhang, YJ, Marotti, L., Self, DW, Tkatch, T ., Baranauskas, G., Surmeier, DJ, Neve, RL, Duman, RS, Picciotto, MR, le Nestler, EJ (1999). Khopolo ea "transaction factor deltaFosB" bokong e laola maikutlo a cocaine. Nature 401, 272-276.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Kim, J., Park, BH, Lee, JH, Park, SK, le Kim, JH (2011). Liphetoho tse ikhethileng tsa mofuta oa selekanyetsong li ka ho pepesa khafetsa ho koae. Biol. Psychiatry 69, 1026-1034.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Knapp, CM, Foye, MM, Cottam, N., Ciraulo, DA, le Kornetsky, C. (2001). Adenosine agonists CGS 21680 le NECA li thibela ts'ebetso ea ho itaola ea koae. Pharmacol. Likokoana-hloko. Behav. 68, 797-803.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Kourrich, S., Rothwell, PE, Klug, JR, le Thomas, MJ (2007). Boiphihlelo ba cocaine bo laola ho leka-lekana ha polasetiki ea synaptic ho li-nucleus accumbens. J. Neurosci. 27, 7921-7928.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Koya, E., Golden, SA, Harvey, BK, Guez-Barber, DH, Berkow, A., Simmons, DE, Bossert, JM, Nair, SG, Uejima, JL, Marin, MT, Mitchell, TB, Farquhar, D., Ghosh, SC, Mattson, BJ, le Tshepo, BT (2009). Ts'ebetso e lebelletsoeng ea li-nucleus tse hlahisoang ke koae e thibela sensitization e ikhethang. Nat. Neurosci. 12, 1069-1073.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Kramer, PF, Christensen, CH, Hazelwood, LH, Dobi, A., Bock, R., Sibley, DR, Mateo, Y., le Alvarez, VA (2011). Dopamine D2 receptor overexpression alters boitšoaro le physiology ho litoeba tsa Drd2-EGFP. J. Neurosci. 31, 126-132.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Kravitz, AV, Freeze, BS, Parker, PR, Kay, K., Thwin, MT, Deisseroth, K., le Kreitzer, AC (2010). Taolo ea boits'oaro ba koloi ea parkinsonian ka taolo ea optogenetic ea basal ganglia circry. Nature 466, 622-626.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Kreitzer, AC, le Malenka, RC (2007). Pholoso-e lipakeng ea Endocannabinoid-mediated ea striatal LTD le likotsi tsa makoloi mefuteng ea lefu la Parkinson. Nature 445, 643-647.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Le Moine, C., Normand, E., le Bloch, B. (1991). Tšobotsi ea phenotypical ea rat striatal neurons e hlalosang mofuta oa D1 dopamine receptor gene. Proc. Natl. Acad. Sci. usa 88, 4205-4209.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Le Moine, C., Normand, E., Guitteny, AF, Fouque, B., Teoule, R., le Bloch, B. (1990). Dopamine receptor gene expression ke enkephalin neurons ho ratbrain. Proc. Natl. Acad. Sci. usa 87, 230-234.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Lee, KW, Kim, Y., Kim, AM, Helmin, K., Nairn, AC, le Greengard, P. (2006). Cocoaine-indied dendritic spine form e entsoeng ka mokokotlo oa D1 le D2 dopamine receptor e nang le li-spiny neurons tse mahareng tsa li-nucleus accumbens. Proc. Natl. Acad. Sci. usa 103, 3399-3404.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Lemberger, T., Parlato, R., Dassse, D., Westphal, M., Casanova, E., Turiault, M., Tronche, F., Schiffmann, SN, le Schutz, G. (2007). Phatlalatso ea Cre recombinase ho li-neuron tsa dopaminocepts. BMC Neurosci. 8, 4. doi: 10.1186/1471-2202-8-4

Text e feletseng ea CrossRef

Lett, BT, Grant, VL, Byrne, MJ, le Koh, MT (2000). Marako a kamore e ikhethileng e nang le mekokotlo ea mabili a matha a hlahisa maemo a ratang sebaka. Takatso ea lijo 34, 87-94.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Lobo, MK, Covington, HE III, Chaudhury, D., Friedman, AK, Letsatsi, H., Damez-Werno, D., Dietz, DM, Zaman, S., Koo, JW, Kennedy, PJ, Mouzon, E ., Mogri, M., Neve, RL, Deisseroth, K., Han, MH, le Nestler, EJ (2010). Tahlehelo ea mofuta o khethehileng oa taolo ea BDNF ea ho supa mimics optogenetic ea moputso oa koae. Science 330, 385-390.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Lobo, MK, Cui, Y., Ostlund, SB, Balleine, BW, le Yang, XW (2007). Taolo ea liphatsa tsa lefutso ea mofuta oa lisebelisoa ka striatopallidal neuron e khethehileng S1P receptor Gpr6. Nat. Neurosci. 10, 1395-1397.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Lobo, MK, Karsten, SL, Grey, M., Geschwind, DH, le Yang, XW (2006). Mokhatlo o hlophisitsoeng oa li-facs oa li-neuron tsa "striatal proion" tsa bongoana le tsa batho ba baholo ba panya. Nat. Neurosci. 9, 443-452.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Lu, L., Koya, E., Zhai, H., Tšepo, BT, le Shaham, Y. (2006). Karolo ea ERK ho lemalla joala ba koae. Trends Neurosci. 29, 695-703.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Mackie, K. (2008). Li-receptor tsa Cannabinoid: li hokae le tseo li li etsang. J. Neuroendocrinol. 20 (Suppl. 1), 10-14.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Maldonado, R., Saiardi, A., Valverde, O., Samad, TA, Roques, BP, le Borrelli, E. (1997). Ho ba sieo ha litlamorao tse khahlisang ho litoeba tse haelloang ke li-receptor tsa dopamine D2. Nature 388, 586-589.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Mattson, BJ, Crombag, HS, Mitchell, T., Simmons, DE, Kreuter, JD, Morales, M., le Hope, BT (2007). Tsamaiso e phetoang ea amphetamine kantle ho cage ea lapeng e ntlafatsa polelo ea Fos e kentsoeng lithethefatsing. Behav. Resin ea Boko. 185, 88-98.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Maze, Mina, Covington, HE III, Dietz, DM, Laplant, Q., Renthal, W., Russo, SJ, Mechanic, M., Mouzon, E., Neve, RL, Haggarty, SJ, Ren, Y. , Sampath, SC, Hurd, YL, Greengard, P., Tarakhovsky, A., Schaefer, A., le Nestler, EJ (2010). Karolo ea bohlokoa ea histonetrylferase G9a ho polasetiki e nang le koae. Science 327, 213-216.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Meisler, MH (1992). Ho kenyelletsa phetoho ea mofuta oa "li-classical" le mofuta oa nova ho litoeba tsa transgenic. Mokhoa oa tloaelo. 8, 341-344.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Miner, LL, Drago, J., Chamberlain, PM, Donovan, D., le Uhl, GR (1995). Khetho ea sebaka sa cocaine e bolokiloeng e le litoeba tse haellang tsa D1. Neuroreport 6, 2314-2316.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Monory, K., Blaudzun, H., Massa, F., Kaiser, N., Lemberger, T., Schutz, G., Wotjak, CT, Lutz, B., le Marsicano, G. (2007). Disekethara tse tsamaeang le litlamorao tsa boits'oaro le boipuso ba Delta (9) -tetrahydrocannabinol ho litoeba. PloS Biol. 5, e269. Doi: 10.1371 / journal.pbio.0050269

Text e feletseng ea CrossRef

Moratalla, R., Robertson, HA, le Graybiel, AM (1992). Matla a taolo ea mofuta oa mofuta oa NGFI-A (zif268, egr1) ho striatum. J. Neurosci. 12, 2609-2622.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Moratalla, R., Vallejo, M., Elibol, B., le Graybiel, AM (1996). D1-class dopamine receptors e susumetsa polelo e phehellang ea protheine e amanang le Fos ho striatum. Neuroreport 8, 1-5.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Nestler, EJ (2005). Na ho na le tsela e tloaelehileng ea limolek'hule ea ho lemalla? Nat. Neurosci. 8, 1445-1449.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Nestler, EJ (2008). Tlhahlobo. Mekhoa e meng ea ho lemalla: karolo ea DeltaFosB. Philos. Trans. R. Soc. London. B Biol. Sci. 363, 3245-3255.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Nestler, EJ, Barrot, M., le Self, DW (2001). DeltaFosB: phetoho e tsitsitseng ea molek'hule bakeng sa ho lemalla. Proc. Natl. Acad. Sci. usa 98, 11042-11046.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Novak, M., Halbout, B., O'Connor, EC, Rodriguez Parkitna, J., Su, T., Chai, M., Crombag, HS, Bilbao, A., Spanagel, R., Stephens, DN, Schutz, G., le Engblom, D. (2010). Ho ithuta ho khothaletsa ho ts'oaroa ha ho batloa ke koae ho hloka li-receptor tsa mGluR5 tse fumanehang ho dopamine D1 receptor-expression neurons. J. Neurosci. 30, 11973-11982.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Numano, R., Szobota, S., Lau, AY, Gorostiza, P., Volgraf, M., Roux, B., Trauner, D., le Isacoff, EY (2009). Nanosculpting e khutlisitse kutloisiso ea wavelength ho GluR e bonoang. Proc. Natl. Acad. Sci. usa 106, 6814-6819.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Nye, HE, Tšepo, BT, Kelz, MB, Iadarola, M., le Nestler, EJ (1995). Boithuto ba pharmacological ba taolo ea kalafo ea antigen e amanang le FOS ea nako e telele ka cocaine ho striatum le nucleus accumbens. J. Pharmacol. Exp. Ther. 275, 1671-1680.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Parkitna, JR, Engblom, D., le Schutz, G. (2009). Ho hlahisa mofuta o mong oa litoeba tsa mofuta oa Cre recombinase tse hlahisang li-bacterial chromosomes tsa baktheria. Mekhoa Mol. Biol. 530, 325-342.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Peakman, MC, Colby, C., Perrotti, LI, Tekumalla, P., Carle, T., Ulery, P., Chao, J., Duman, C., Steffen, C., Monteggia, L., Allen, MR, stock, JL, Duman, RS, Mcneish, JD, Barrot, M., Self, DW, Nestler, EJ, le Schaeffer, E. (2003). Polelo e sa bonahaleng, ea 'mala o ikhethang sebakeng sa bokaholimo ba motsoako o mobe oa c-Jun ho litoeba tsa transgenic e fokotsa maikutlo a cocaine. Resin ea Boko. 970, 73-86.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Batho, LL, Uzwiak, AJ, Guyette, FX, le Bophirima, MO (1998). Tonic inhibition ea li-nucleus tse le 'ngoe li bokella li-neurons ka hara rat: mokhoa o atileng empa o sa khetholle mokhoa oa ho thunya o susumetsoang ke lithuto tsa tsamaiso ea koae. Khopolo-taba 86, 13-22.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Perrotti, LI, Hadeishi, Y., Ulery, PG, Barrot, M., Monteggia, L., Duman, RS, le Nestler, EJ (2004). Ho hlahisoa ha deltaFosB ka likarolo tsa boko tse amanang le moputso kamora khatello ea maikutlo e sa foleng. J. Neurosci. 24, 10594-10602.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Pierce, RC, Bell, K., Duffy, P., le Kalivas, PW (1996). Phetisetso ea "cocaine augments" e fetisang phepelo ea amino acid e phetoang. J. Neurosci. 16, 1550-1560.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Risinger, FO, Freeman, PA, Rubinstein, M., Low, MJ, le Grandy, DK (2000). Ho haelloa ke ts'ebetso ea tsamaiso ea ethanol ho dopamine D2 receptor Knoutout. Psychopharmacology (Berl.) 152, 343-350.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Robertson, HA, Paul, ML, Moratalla, R., le Graybiel, AM (1991). Pontšo ea gene ea c-fos ea mantlha pejana ho basal ganglia: ho kenngoa ka litlhare tsa dopaminergic. E ka khona. J. Neurol. Saense 18, 380-383.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Russo, SJ, Dietz, DM, Dumitriu, D., Morrison, JH, Malenka, RC, le Nestler, EJ (2010). Syndicse e lemalloang: mekhoa ea synaptic le polasetiki ea moralo nucleus accumbens. Trends Neurosci. 33, 267-276.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Schiffmann, SN, Libert, F., Vassart, G., le Vanderhaeghen, JJ (1991). Ho ajoa ha adenosine A2 receptor mRNA bokong ba motho. Neurosci. Lett. 130, 177-181.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Schiffmann, SN, le Vanderhaeghen, JJ (1993). Li-receptors tsa Adenosine A2 li laola polelo ea gene ea striatopallidal le striatonigral neurons. J. Neurosci. 13, 1080-1087.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Boithati, DW (2010). "Dopamine receptor subtypes ka moputso le ho khutlela hape," ho Li-Dopamine Receptors, ed. KA Neve (New York, NY: Humana Press), 479-523.

Self, DW, Barnhart, WJ, Lehman, DA, le Nestler, EJ (1996). Phetohelo e hanyetsang ea boitšoaro bo batlang koae ka koae ke D1- le D2-joalo ka dopamine receptor agonists. Science 271, 1586-1589.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Surmeier, DJ, Ding, J., Day, M., Wang, Z., le Shen, W. (2007). D1 le D2 dopamine-receptor modulation ea striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci. 30, 228-235.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Surmeier, DJ, Sefela, WJ, le Yan, Z. (1996). Polelo e kopanetsoeng ea li-receptor tsa dopamine ho li-neuron tsa spiny neurons tse kahare. J. Neurosci. 16, 6579-6591.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Thanos, PK, Michaelides, M., Umegaki, H., le Volkow, ND (2008). Ts'ebeliso ea D2R ea "DNA" ho "nucleus" e kenyelletsa ho ikarola ha koae ka likhoto. Synapse 62, 481-486.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Thanos, PK, Taintor, NB, Rivera, SN, Umegaki, H., Ikari, H., Roth, G., Ingram, DK, Hitzemann, R., Fowler, JS, Gatley, SJ, Wang, GJ, le Volkow , ND (2004). Ho fetisoa ha mofuta oa DRD2 ho mantlha ho bokella likotlo tsa joala tse ikhethileng le tse sa tlatselletseng ho jala joala. Joala. Clin. Exp. Res. 28, 720-728.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Thomas, MJ, Beurrier, C., Bonci, A., le Malenka, RC (2001). Ho sithabela maikutlo ha nako e telele ho li-nucleus tsa li-nucleus: li-link tsa neural tsa maikutlo a boitšoaro ho cocaine. Nat. Neurosci. 4, 1217-1223.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Uslaner, J., Badiani, A., Letsatsi, HE, Watson, SJ, Akil, H., le Robinson, TE (2001a). Tikoloho ea tikoloho e hlophisa bokhoni ba koae le amphetamine ho susumetsa polelo ea c-fos mRNA ho neocortex, nucleus ea caudate le li-nucleus. Resin ea Boko. 920, 106-116.

Text e feletseng ea CrossRef

Uslaner, J., Badiani, A., Norton, CS, Letsatsi, HE, Watson, SJ, Akil, H., le Robinson, TE (2001b). Amphetamine le cocaine e etsa hore ho be le mekhoa e fapaneng ea polelo ea c-fos mRNA ka har'a striatum le subthalamic nucleus ho latela maemo a tikoloho. EUR. J. Neurosci. 13, 1977-1983.

Text e feletseng ea CrossRef

Valjent, E., Bertran-Gonzalez, J., Herve, D., Fisone, G., le Girault, JA (2009). Ho sheba BAC ho ho supa matšoao a hlakileng: tlhahlobo e ikhethang ea sele ho litoeba tse ncha tsa transgenic. Trends Neurosci. 32, 538-547.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Valjent, E., Corvol, JC, maqephe, C., Besson, MJ, Maldonado, R., le Caboche, J. (2000). Ho kenyelletsoa ha papali ea likhase tse tsoang ho li-extracellular-regated lapa bakeng sa thepa e lefisang koae. J. Neurosci. 20, 8701-8709.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Vialou, V., Robison, AJ, Laplant, QC, Covington, HE III, Dietz, DM, Ohnishi, YN, Mouzon, E., Rush, AJ III, Watts, EL, Wallace, DL, Iniguez, SD, Ohnishi, YH, Steiner, MA, Warren, BL, Krishnan, V., Bolanos, CA, Neve, RL, Ghose, S., Berton, O., Tamminga, CA, le Nestler, EJ (2010). DeltaFosB ho li-circuits tsa moputso oa boko li thusa ho sebetsana le khatello ea maikutlo le likarabo tse khahlanong le khatello ea maikutlo. Nat. Neurosci. 13, 745-752.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Volgraf, M., Gorostiza, P., Numano, R., Kramer, RH, Isacoff, EY, le Trauner, D. (2006). Taolo ea allosteric ea ionotropic glutamate receptor e nang le switch switch. Nat. Khemo. Biol. 2, 47-52.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Volkow, ND, Fowler, JS, Wang, GJ, Baler, R., le Telang, F. (2009). Karolo ea ho etsisa karolo ea dopamine tlhekefetsong ea lithethefatsi le bokhoba ba lithethefatsi. Neuropharmacology 56 (Suppl. 1), 3-8.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Volkow, ND, Fowler, JS, Wang, GJ, le Swanson, JM (2004). Dopamine ts'ebelisong le lithethefatsi: litlamorao ho tsoa ho lithuto tsa monahano le litlamorao tsa kalafo. Mol. Psychiatry 9, 557-569.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Welter, M., Vallone, D., Samad, TA, Meziane, H., Usiello, A., le Borrelli, E. (2007). Ho ba sieo ha dopamine D2 receptors ho hlakisa taolo e thibelang likotlo tsa boko e sebetsang ke cocaine. Proc. Natl. Acad. Sci. usa 104, 6840-6845.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Werme, M., Messer, C., Olson, L., Gilden, L., Thoren, P., Nestler, EJ, le Brene, S. (2002). Delta FosB e laola mabili a tsamaeang. J. Neurosci. 22, 8133-8138.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

E tšoeu, FJ, Hu, XT, Zhang, XF, le Wolf, ME (1995). Tsamaiso e pheta-phetoang ea likarabo tsa "cocaine" kapa "amphetamine alters" ho hlahisa glutamate tsamaisong ea dopamine ea mahloaccumbens. J. Pharmacol. Exp. Ther. 273, 445-454.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Bohlale, RA (2004). Dopamine, ho ithuta le tšusumetso. Nat. Rev. Neurosci. 5, 483-494.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Wolf, ME (2010). Taolo ea ts'ebetso ea khoebo ea li-receptor ea AMPA ka har'a nucleus e bokelloa ke dopamine le cocaine. Neurotox. Res. 18, 393-409.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Wu, YI, Frey, D., Lungu, OI, Jaehrig, A., Schlichting, I., Kuhlman, B., le Hahn, KM (2009). Rac e kentsoeng liphatsa tsa lefutso e laola tšusumetso ea lisele tse phelang. Nature 461, 104-108.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Bacha, ST, Porrino, LJ, le Iadarola, MJ (1991). Cocaine e etsa liprotheine tse matlafatsang tsa c-fos-immunoreactive ka li-receptor tsa dopaminergic D1. Proc. Natl. Acad. Sci. usa 88, 1291-1295.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Zachariou, V., Bolanos, CA, Selley, DE, Theobald, D., Cassidy, MP, Kelz, MB, Shaw-Lutchman, T., Berton, O., Sim-Selley, LJ, Dileone, RJ, Kumar, A., le Nestler, EJ (2006). Karolo ea bohlokoa ea DeltaFosB ho li-nucleus e bokellanang ketsong ea morphine. Nat. Neurosci. 9, 205-211.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Zhang, J., Zhang, L., Jiao, H., Zhang, Q., Zhang, D., Lou, D., Katz, JL, le Xu, M. (2006). c-Fos e thusa ho fumana le ho felisoa ha liphetoho tse phehellang tsa koae. J. Neurosci. 26, 13287-13296.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed | Text e feletseng ea CrossRef

Zhang, XF, Hu, XT, le White, FJ (1998). Plasmine ea seleng ka botlalo ho tloheng ha koae: metsoako e khutsitseng ea sodium ho li-nucleus e bokella li-neuron. J. Neurosci. 18 488-498.

Bapmed Abstract | Phatlalatso e feletseng ea Pubmed

Keywords: methapo ea kutlo e bohareng, ho lemalla, li-bokellase tsa nucleus, mofuta oa sele, mofuta oa D, o ikhethang1+ Li-MSN, D2+ Li-MSN, koae, dopamine

Tlhaloso: Lobo MK le Nestler EJ (2011) Ketso ea ho leka-lekanya ea litheko lemating la lithethefatsi: likarolo tse ikhethileng tsa tsela e otlolohileng e sa tobang le e sa tsamaeang hantle ea methapo ea methapo. Ka pele. Neuroanat. 5: 41. Doi: 10.3389 / fnana.2011.00041

Re amohetse: 12 May 2011; Papali e ntseng e emetse e phatlalalitsoe: 31 May 2011;
E amohetse: 05 Julayi 2011; E hatisoa Inthaneteng: 18 July 2011.

E hlophisitsoeng ke:

Emmanuel Valjent, Univesithi ea Montpellier 1 & 2, Fora

Hlahloba by:

Bruce Thomas Tšepo, Setsi sa Naha sa Tlhekefetso ea Lithethefatsi, USA
John Neumaier, Univesithi ea Washington, USA

Copyright: © 2011 Lobo le Nestler. Ena ke sengolo se bulehileng se fihlellang laesense e seng e ikhethileng pakeng tsa bangoli le Frontiers Media SA, e lumellang tšebeliso, phetiso le tlhahiso liphatlalatsong tse ling, ha feela bangoli ba mantlha le mohloli ba ngolisitsoe 'me maemo a mang a Frontiers a tsamaisoa.

Ngollano: Eric J. Nestler, Lefapha la Neuroscience, Friedman Brain Institute, Mount Sinai School of Medicine, Sebaka se le seng sa Gustave L. Levy, Box 1065, New York, NY 10029-6574, USA. lengolo-tsoibila: [imeile e sirelelitsoe]