Onyinye Nyefe N'ihe Na - ebute Ọganihu Na Mmalite Na Nsogbu Mberede (2017)

. 2017; 11: 77.

E bipụtara na 2017 Apr 28. doi:  10.3389 / fnbeh.2017.00077

PMCID: PMC5408019

nkịtị

N'ime afọ iri atọ gara aga, ọ bịara doo anya na arụmọrụ nke netwọkụ nke mpaghara ụbụrụ na-ejikọ ọrụ maka ịkwụ ụgwọ ọrụ na akparamaagwa akparamaagwa na-emetụta nsogbu ọnọdụ obi dị iche iche, gụnyere ịda mba na nchegbu. O dokwara anya na mgbanwe na-akpata nrụgide na ọrụ ụgwọ ọrụ na-akpata ma omume nkịtị ma ọrịa na-akpata mgbanwe na nkwupụta mkpụrụ ndụ. N'ebe a, anyị na-anwa ịkọwapụta ụgwọ ọrụ na ịchọpụta onyinye ndị amaara na nke pụrụ ịdabere na mgbanwe mgbanwe na mkpụrụedemede mkpụrụ ndụ n'ime sekit a maka mgbanwe nrụgide sitere na omume metụtara nsogbu mgbanwe ọnọdụ, ma gosipụta ụfọdụ n'ime mmetụta ndị a na-emetụta site na mkpughe. ị drugsụ ọgwụ ọjọọ. Anyị na-elekwasị anya na usoro nke mkpụrụ ndụ ihe mbụ dị n'oge na-achịkwa site na nrụgide dị n'ime sekit a na njikọ ha, ma nyocha nke ọma ma dịtụ akụkọ, na ọrụ sekit na omume ndị metụtara ụgwọ ọrụ na-esote. Anyị na-ekwubi na IEGs na-arụ ọrụ dị mkpa na nrụpụta nrụgide na-agbanwe nrụghachi nke circuitry, na ha nwere ike ịrụ ọrụ dị ka mgbochi nke usoro ihe omimi, usoro ekwentị na ọgwụgwọ.

Keywords: ịda mba, usoro ụgwọ ọrụ, ngwa ngwa mmalite mbụ (IEG), FosB / ΔFosB, CREB, accumbens, hippocampus, nsogbu ọnọdụ.

Okwu Mmalite

Neurocircuitry agbanweela iji kwụọ ụgwọ omume ndị na-enye aka na mgbakwunye ekike na mmetụta nke ihe ụtọ, na-akpali mkpụrụ ndụ mmadụ iji kpọrọ ihe, ma na-emeghachi omume ndị na-eme ka ohere nke ịgbasa ihe ọmụmụ mkpụrụ ndụ ihe nketa ha. Ndị a nwere ike ịgụnye inwe mmekọahụ, iri nri ụfọdụ, ilekọta ụmụ, ma ọ bụ itinye aka na nnọkọ oriri. Agbanyeghị, gburugburu ebe obibi mmadụ ugbu a, nke jupụtara ụba na ohere inweta ihe na-atọ ụtọ, nwere ike ime ka mmelite ụgwọ ọrụ kwalite nchụso, dị ka ịingụ ọgwụ ma ọ bụ ọgwụ riri ahụ (Berridge na Kringelbach, ). N'aka nke ọzọ, ụkọ na nhazi ụgwọ ọrụ na-eso akpata mgbaaka anhedonic nke nsogbu ọnọdụ mmụọ dịka ịda mba (Nestler, ; Luking et al., ), yana ọgwụgwọ na nyocha ugbu a na nsogbu ọgba aghara na-elekwasị anya na ụgwọ ọrụ mmegharị circuitry na usoro ndị nwere ike itinye aka na nhazi ụgwọ ọrụ rụrụ arụ.

Omume ịkwụghachi ụgwọ na-enweta ihu ọma n'ihi na ha na-eme ka ọ dị ike. Usoro a choro ka ha: (1) nye mmetuta obi uto (obi uto), (2) ime ka muta muta, na (3) weputa agwa ndi ozo (dika nri, itule, imekorita, wdg). Yabụ, rewardlọ ọrụ ụgwọ ahụ ga-ejikọ ozi sitere n'ụkpụrụ ụbụrụ nke na-eme ka mmadụ nwee obi uto, nhazi na ichekwa ihe, yana ime mkpebi na nsonaazụ akparamaagwa. Ọ pụtala nke ọma n'ime iri afọ abụọ gara aga na mgbanwe na mkpụrụ ndụ ihe ndekọ n’ime mkpụrụgharị ụgwọ ọrụ a so mee ka e nwee nsogbu mgbanwe omume (Nestler, ). Mgbanwe ndị a metụtara ọrịa nwere ike ịgụnye usoro dịgasị iche iche dịka ngbanwe histone na DNA, nkwupụta RNA na-enweghị mkpụrụ ego, yana ntinye ya na ntinye ya (Dalton et al., ; Geaghan na Cairns, ; Nestler, ). Ihe ngosipụta nke ọtụtụ ihe ntụgharị na-emetụta usoro ndị a bụ nke arụ ọrụ neuronal na-achịkwa ya, ihe ndị dị otú ahụ na-abanyekwa na klaasị ụmụ irighiri ihe akpọrọ ngwa ngwa okike (IEGs). IEG ndị a na-anọchite anya usoro kachasị mma maka ọrịa ndị metụtara anhedonia, ebe a na-agbanwe ụgwọ ọrụ neuronal n'ọtụtụ ịda mba (Russo na Nestler, ; Lammel et al., ), ma otua isi dikwa na egosiputa otutu IEGs n’otu usoro (Reul, ; Nestler, ). Ya mere, iji kpughee usoro omiology nke nsogbu ọnọdụ mmadụ, ọ dị oke mkpa na anyị kpughere iwu nke IEGs na sekit dị iche iche n'okpuru ọnọdụ basal na ọrịa. Nyocha a ga - ekpuchi ọganihu na ịchọpụta usoro na ebumnuche nke IEGs n'ime mpaghara ụbụrụ nke nwere nchịkọta ngagharị, yana ihe akaebe ugbu a na-ejikọta ụgwọ ọrụ IEGs na mmeghachi omume nrụgide na nsogbu ọnọdụ.

Cortico-basal ganglia na-akwụghachi ụgwọ ọrụ

Akụkụ dị mkpa nke sekọndị ụgwọ ọrụ bụ ntọhapụ nke dopamine (DA) site na mpaghara ventral tegmental (VTA) n'ime mpaghara ụbụrụ limbic na-achịkwa amụma, nghọta na nhazi nke mkpali na-akwụghachi ụgwọ. VTA DA neurons nwere nnukwu atụmanya maka cortex prefrontal (PFC; ụzọ mesocortical) yana nchikota ọnụọgụ (NAc; ụzọ mesolimbic), kamakwa ọrụ ngo na hippocampus, amygdala, na mpaghara mpaghara ndị ọzọ. Mesocortical DA na-eche na ọ na-etinye aka na nzaghachi uche na njikwa nke cognition (Nestler et al., ), ebe mesolimbic DA nwere ọdịnala nwere njikọta ụgwọ ọrụ na akparamagwa. Mwepụta Mesolimbic DA na - eme ka ndị na - anabata ndị na - anabata dopamine (DRs) na NAc ọkara spiny neurons (MSNs), mkpụrụ ndụ GABAergic nwere mmadụ abụọ dị iche na - egosipụta nke kacha D1 ma ọ bụ D2 DRs (Surmeier et al., ; Lobo, ). D1 MSNs mejuputara uzo nke 'uzo', nke n'ikpeazụ nwekwuo ike thalamocortical drive, ebe D2 MSNs na-eme ụzọ 'zighi ezi', nke na-ebute mbelata thalamocortical drive. N'ihi na D1 DRs na-abawanye azịza maka excitation nke glutamatergic ebe D2 DR na-ebelata ohere a na-enweghị atụ, Mwepụta VTA DA na-eme ka ụzọ a na-agazi agazi ka ị na-etinye breeki n'ụzọ adịghị mma, yana njikọ jikọtara nke ike cortical drive.

NAc MSNs na-enweta ntinye glutamatergic site na ọtụtụ cortical na akụkụ limbic, gụnyere nkewa na etiti akụkụ nke PFC, ventral hippocampus (vHPC), basylateral amygdala (BLA), na medial thalamus (Sesack na Grace, ; Floresco, ). Ihe ntinye PFC na NAc na-achịkwa omume ebumnuche, dị ka ịchọrọ ma rie ihe / ihe omume metụtara ụgwọ ọrụ, gụnyere nri, mmekọahụ, ọgwụ, na mmekọrịta mmekọrịta (Kalivas et al., ; Gruber et al., ), ịnye “nchịkwa nchịkwa” a chọrọ maka atụmatụ na ịrụ ọrụ iji nweta ụgwọ ọrụ. ntinye vHPC na NAc ga - enye gị ozi gbasara ọnọdụ ọjọọ na - emetụta ọnọdụ dị na oghere na ahụmịhe sitere na mmụta mmetụta. Nke a metụtara ma ọnọdụ mmetụta uche dị mma ma ọ bụ nke na-adịghị mma, ntụgharị, ụgwọ ọrụ na mmụta sitere na ya, gụnyere ọnọdụ ụjọ na-atụ, omume nri, yana azịza ọgwụ ọjọọ (Vezina et al., ; Fanselow, ; Kanoski na Grill, ). Ọ bụ ezie na ọrụ mmemme BLA na nyocha nke BLA na mpaghara ụbụrụ ndị ọzọ na-achịkwa mmụta na omume metụtara, ntinye glutamatergic sitere na BLA na NAc MSNs na-abawanye ụgwọ ọrụ na-achọ ma na-akwado agbamume dị mma (Ambroggi et al., ; Stuber et al., ; Janak na Tye, ).

Ọtụtụ n'ime mpaghara ntinye glutamatergic NAc a na-emekwa onwe ha ọrụ, NAc MSN na-eziga na ịnata atụgharị GABAergic na VTA kwa. Ihe a rụpụtara na netwọkọ cortico-basal ganglia ụgwọ ọrụ (Sesack na Grace, ; Floresco, ), ụdị ngosipụta nke gosipụtara ebe a (ọgụgụ (Figure1A) .1A). Ọrụ kachasị nke netwọkụ a bụ ịhazi ma jikọta akara cortical / limbic glutamatergic nke na-anọchite anya njikwa njikwa, ebe nchekwa, na mmetụta na nhazi ụgwọ ọrụ dopaminergic iji chịkwaa nsonaazụ thalamocortical nke na-eduzi omume. Na nkenke, ọtụtụ n'ime mpaghara tinyere aka na-enwe mgbanwe ogologo oge na nkwupụta mkpụrụ ndụ, na arụ ọrụ sel, ọtụtụ mgbe n'ihi nsonaazụ nchekasị, nke ahụ nwere ike ibute nsogbu metụtara ọnọdụ, mgbanwe ndị a na-ebute, n'otu akụkụ, site na nkwupụta mkparị. na ọrụ nke IEGs. Nke a na-apụtakarị ìhè na mgbanwe mgbanwe nke nrụgide n'ụdị usoro akwara ụgwọ ọrụ.

Nyocha 1  

Cortico-basal ganglia na-akwụghachi ụgwọ netwọkụ. (A) Ngwongwo ngwongwo (NAc) na-ejikọta ntinye glutamatergic (red) nke na-ahazi ohere (spinalal ventral hippocampus, vHPC), mmetụta uche (basylateral amygdala, BLA), na onye isi (prefrontal cortex, PFC) omume, yana ...

Nsogbu ndagide akwara na-adịghị ala ala, ihe atụ nke nkụda mmụọ, na-ebute mmụba dendritic spain dens na NAc MSNs (ọgụgụ (Figure1B) .1B). Ọkpụkpụ MSN dendritic bụ ahaziri njikọ nke glutamatergic ndenye, yana ọnụọgụ na ụdị nke spine na-anọchite ọnụọgụ na ike nke ihe ndị ahụ. Mmụba nke spain a hụrụ na NAc mgbe nsogbu ọgba aghara mmekọrịta na-adịghị ala ala (CSDS) bụ isi n'ihi mmụba nke ọgịga na-adị nkọ, nke na-eto eto, na enweghị mgbanwe na mkpụrụ osisi etolite etolite etolite etolite (Christoffel et al., ). Mkpakọ Stubby nwere njikọ na obere postsynapti densities (PSDs) na mmeghachi ike na-esighi ike maka nri nri, mana mmụba na njupụta ha mgbe nrụgide nwere ike ịnọchite anya mmụba nke glutamatergic na-egosi NAc, ọ na-esonye na mmụba na ọnụọgụ (mana ọ bụghị njupụta) nke obere ikike pụrụ iche postsynaptik (mEPSPs; Christoffel et al., ). Na mgbakwunye na usoro nrụgide dị ka CSDS, nchịkwa nke psychostimulants dịka cocaine na-abawanye njupụta nke spain dendritic, ọkachasị n'ihi mmụba nke ọnụ ọgụgụ dị warara (Robinson na Kolb, ; Russo et al., ), a udi na-atụle ọmụmụ. Agbanyeghị, na ọdịiche dị na nrụgide, nchịkwa ọgwụ na-akpali akpali na-abawanye dendritic spaine complex na NAc MSNs, na ọtụtụ spines na-egosi njikwa ọtụtụ isi (Robinson na Kolb, ; Ọgụgụ Ihe osise .1B) .1B). Mmụba a na mgbagwoju anya nwere ike ịnọchite anya nhazi na mmụba na sigasị synaptik, na-egosi mgbanwe na ọrụ sekit mgbe ahụmịsịrị ọgwụ. Ọtụtụ ngwaahịa mkpụrụ ndụ ihe nketa nwere ike itinye aka na nhazi nke spain dendritic na steeti ndị nrụgide na ọgwụ kpughere, gụnyere ọtụtụ IEG ndị a tụlere n'okpuru (dịka, ΔFosB, CREB; Maze et al., ; Russo et al., ). Nghọta dị mma nke njikọ dị n'etiti ngosipụta IEG na nhazi nke plasticity nke arụ ọrụ dị oke mkpa maka mmepe nke nghọta anyị banyere ọnọdụ na ihe riri ahụ.

CAMP mmeghachi omume mmechi na-egbochi (CREB)

CREB bu ntughari nke jikọrọ ya na ihe mmeghachi omume nke CAMP (CRE) na DNA na nzaghachi nke ntinye uzo na-egosi ihe di na CAMP, Ca.2+/ stabodulin, ma ọ bụ ihe dị iche iche etolite na / ma ọ bụ cytokines. Ntughari nke CREB nke ntughari site na nkpuru mbu (Figure2) 2na-achịkwa site na phosphorylation na serine 133 site na protein kinase A (PKA, down of cAMP), Ca2+/ udoodulin-protein protein kinase IV (CaMKIV, ala nke Ca2+), na / ma ọ bụ akara MAP kinase (ala nke ihe na uto na cytokines; Kida na Serita, ). Mkpụrụ osisi Ser133 phosphorylation na-akwalite mmekorita ya na protein CREB-bonding (CBP), usoro dị oke mkpa maka ịgbagharị transcriptional (Chrivia et al., ). Ihe omumu nke mbu na nke kachasi nke oru CREB na oru ogwu bu na njigide ntughari nkpuru site na ike nke synapses na ncheta. CREB dị oke egwu maka ebe nchekwa na synaptic plasticity na invertebrate sea slug Aplysia (Dash et al., ; Kandel, na mkpụrụ osisi na-efe efe (Yin et al., ), na ebe nchekwa nwere ogologo oge na ụmụ oke CREB na-arụ ọrụ, mana ọ na-eme ka ọ dị mma na ụmụ oke arụ ọrụ CREB, nke bụ isi n'ihi ọrụ ya na hippocampus (nke a chịkọtara na Kida na Serita, ).

Nyocha 2  

Alingzọ mgbaàmà na-eduga n'ịrụ ọrụ CREB. Ihe nrịba ama nke extracellular na ngbanwe nke membrane nwere ike mee ka ndi nnabata ya na ọwa gunyere: G-protein coupled receiptors (GPCR), NMDA ụdị-glutamate receiptors (NMDAR), voltaji gated Ca2+ ọwa (VGCC), ...

A na - akpalite CREB na NAc site na ikpughere ndị nrụgide dị iche iche, na ntinye aka ya na NAc ejikọtara ọnụ na mmeghachi omume mmetụta dị iche iche, na nkwekọrịta n'ozuzu ya bụ na ịgbado ọkụ na-adịghị ala ala nke CREB na NAc na-eduga na anhedonia ebe mgbochi nke ọrụ CREB na NAc na-akwalite ụgwọ ọrụ (Barrot et al., ; Carlezon et al., ). Ọzọkwa, ọrụ CREB belata na NAc yiri ka ọ nwere mmetụta antidepressant dị na ọtụtụ ụdị nrụgide (Pliakas et al., ; Conti et al., ; Newton et al., ; Covington et al., ), na-atụ aro na ịgbalite nrụgide CREB na NAc nwere ike itinye aka na etiology nke ịda mba. Agbanyeghị, ihe dị iche na - egosi na ọ bụ eziokwu banyere omume ndị na - akpata nchekasị, n'ihi na ọrụ NAc CREB na - abawanye na - egosi nhụjuanya mgbe mgbochi nke NAc CREB na - akwalite nchegbu (Barrot et al., , ; Wallace et al., ), na-egosi na ịchịkwa ọrụ NAc CREB nwere ike ọ gaghị abụ ọgwụgwọ ọgwụgwọ dị mfe maka ịgwọ nsogbu ọgba aghara.

N'ụzọ dị iche na ọrụ ya na NAc, Ntugharị CREB na hippoftọs na-arụpụta ọgwụ mgbochi (Chen et al., ), a na - eme ka ya na hippopolọsị n'ọtụtụ ọgwụ na - egbochi ahụhụ (Nibuya et al., ; Thome et al., ). Otu n'ime ọtụtụ mkpụrụ ndụ ihe nketa akọwapụtara CREB bụ ihe kpatara ụbụrụ neurotrophic (BDNF), BDNF na-abanyekwa na hippocampus site n'aka antidepressants (Nibuya et al., ) ọ bụkwa isi ihe na - ebubata ọgwụ na - egbochi mmerụ ahụ (Björkholm na Monteggia, ). Edeela ụzọ a CREB-BDNF iji mee ka neurogenesis hippocampal bụrụ ihe dị mkpa iji mee ihe na - emegide mmụọ (Duman, ; Carlezon et al., ). Ọ bụ ya mere na dysfunction nke CREB na hippophous nwere ike ịda mbà n'obi abụọ na ụfọdụ nke mmụọ ọgụgụ isi na-emetụta nrụgide na-adịghị ala ala nke na-emetụtakarị nsogbu mgbanwe ọnọdụ (Bortolato et al., ). Ọ dịkwa mkpa ịmara na CREB na-achịkwa ngosipụta nke ọtụtụ ndị ọzọ IEG na-ejikọta na mmeghachi omume nrụgide na ịda mbà n'obi, gụnyere FosB, c-fos, na Arc (lee n'okpuru), yabụ nwere ike rụọ ọrụ dị ka onye ọka iwu na-ahụ maka transcriptal na-arụ ọrụ. omume na nrụgide n'oge ụgwọ ọrụ niile.

Ihe nchebe AP-1-c-fos, FosB / ΔFosB, Jun

Protin activator 1 (AP1) bụ ihe mejupụtara heterodimers n'etiti protein Fos, protein ezinụlọ, ihe nchekwa Jun, na / ma ọ bụ ihe na - eme ka transperent transperent (ATF) mee nke, mgbe ha zukọrọ, na-arụ ọrụ dị ka ndị nwere ikike na ndị na - achịkwa kpọmkwem usoro nke usoro ọmụmụ. Ihe mgbagwoju anya AP1 nwere Fos-Jun heterodimers nke na-eji leucine zippers dị na protein abụọ maka mbelata na mpaghara bụ isi nke na - emekọrịta ihe na DNA. Ezinaụlọ Fos nke ihe ntụgharị bụ ihe mejupụtara c-fos, FosB (na ụdị ya dị iche iche, osFosB na Δ2ΔFosB), Fra1, na Fra2, ihe niile na-akpali site na ọrụ neuronal. c-fos na aru oru nke ukwu, ma nwe ndu, site na nkeji rue rue otu di na nwunye (Sheng na Greenberg, ; Kovács, ; Ferrara et al., ), na hypothesized iji nwaa ụdị mkpụrụ ndụ ihe nketa dịgasị iche metụtara ihe dị iche na sel, mmepe nke synapse, plastic synaptik, na mmụta (Alberini, ; West na Greenberg, ). Njikọ ya doro anya na ọrụ cellular emeela ka ejiri ya mee ihe dịka akara aka nke mpaghara ụbụrụ na akparamagwa na ọnọdụ ahụike, agbanyeghị enye ihe akaebe doro anya maka ebumnuche nke c-fos kpọmkwem, na arụ ọrụ ya na neuronal ọrụ ka na-agagharị. A na - eme ka ya na njem nkwụghachi ụgwọ niile site na mkpali mmụọ niile (Kovács, ; Cruz et al., ; Nestler, ), mana ọrụ ọrụ ya na nsogbu ọgba aghara na ọzịza antidepressant aghị nke ọma.

FosB bụ nke FosB gene ma na-ekerịta ọtụtụ njirimara na c-fos: FosB nwere ngosipụta basal dị ala ma bụrụ nke na-eme n'ụzọ dị omimi ma dị ike site na ọrụ neuronal (Nestler et al., ), yana obere ndụ dị mkpụmkpụ na sel nke c-fos (Dobrazanski et al., ; Ferrara et al., ; Ulery et al., ). Splice mgbanwe nke FosB Site na mkpụrụ ndụ ihe ọmụmụ na - ewepụta codeon na - akaghi aka nke na - ebute protein ΔFosB nke etinyere, nke enweghị ngalaba abụọ c-terminal degron na-agbazinye ya ụba nkwụsi ike (Carle et al., ). Ọtụtụ IEGs ndị ọzọ nwere ọkara ndụ nke awa ole na ole, ebe ΔFosB nwere ndụ ogologo oge na-enweghị atụ, ruo ụbọchị 7. na vivo (Olile anya et al., ; Andersson et al., ; Ulery-Reynolds et al., ), ime ya akara ala ala ọrụ neuronal. ΔFosB na-abanye na nhazi ụgwọ ọrụ niile site na nrụgide na-adịghị ala ala (Perrotti et al., ) na mkpughe nke na - adịghị ala ala (Vialou et al., ), dịkwa ka CREB (nke dị mkpa maka ntinye ΔFosB, Vialou et al., ), mmetụta omume nke nkwupụta ya dị iche site na mpaghara ụbụrụ. Na NAc, ΔFosB na-akpata nrụgide na-adịghị ala ala nke na-adịghị ala ala, na ntinye ya dị ukwuu na ụmụ anụmanụ na-ejikọ mmetụta nke nrụgide karịa na ndị nwere ike ịda mbà n'obi dị ka phenotype (Vialou et al., ). Ọzọkwa, ΔFosB induction na NAc na-akwalite nkwụghachi nke nrụgide na-adịghị ala ala ma ọ dị mkpa maka mmetụta antidepressant nke SSRI dịka fluoxetine (Vialou et al., ), doro anya site na mgbanwe nke AMPA nnabata subunit ngosipụta na usoro nchịkwa nke okwu CaMKIIα (Vialou et al., ; Robison et al., ). Ntinye ya site na nrụgide na ụmụ oke ụmụ irighiri ihe pụtara MSNs ụdị D1 na NAc, ebe a na-ahụ ọkwa dị omimi n'ime ụdị D2 ụdị MSN nke ụmụ oke nwere oke (Lobo et al., ). N'ezie, oke specificFosB dị na D1 MSNs yiri ka ọ nwere mmetụta antidepressant (Vialou et al., ; Muschamp et al., ; Donahue et al., ), ọ na-agbanwekwa usoro nke glutamatergic synapses na neuron ndị a akọwapụtara. ΔFosB na-akwalite ngosipụta nke spain dendritic dị obere na nke nnupu isi, yana mmụba ọnụ na synapses dị jụụ, na D1 mana ọ bụghị D2 MSNs (Grueter et al., ), na-atụ aro na ọ selectively na-agbanwe glutamatergic ndenye na NAc kpọmkwem ụzọ ọpụpụ neurons, ozugbo modulating ụgwọ ọrụ.

Na PFC na-atụgharị uche, ΔFosB na-ahọrọ n'ụzọ dị oke egwu na ụmụ oke nwere ike ịda mba na-adịghị ala ala (Vialou et al., ). Ọzọkwa, na mmegide kpọmkwem na nsonaazụ ya na NAc D1 MSNs, mgbochi osFosB na mPFC neurons na-akwalite nkwụsi ike na nrụgide na-adịghị ala ala, ebe ΔFosB overexpression na-eme ka ikike ịbanye na ya, opekata mpe na akụkụ site na ntinye nke cholecystokinin-B nnata (Vialou et al., ). Nsonaazụ a gosipụtara na ọ bụ onye okwu ΔFosB na-agbagha site na mPFC neurons nke na-ebido NAc, na-ekwusi ike na ọdịdị dị omimi nke nkwụsi ike sitere na nkwụghachi ụgwọ. Anyị kọrọ na nso nso a na ngosipụta nke ΔFosB na hippopolfus dị oke mkpa maka ọtụtụ usoro mmụta (Eagle et al., ), mana ọrụ hippocampal ΔFosB na mmeghachi omume nrụgide na nsogbu ọnọdụ, ma na mpaghara yana na nyocha nke NAc ma ọ bụ PFC, ka amabeghị.

Ọbara nzaghachi (SRF)

SRF bu ihe ntughari nke jikọtara ya na usoro nzaghachi okwu ahụ a na-achọta na ndị na-akwalite ọtụtụ IEG na ọtụtụ mkpụrụ ndụ ihe atụ akọwapụtara (Knöll na Nordheim, ). N'ime ụbụrụ okenye, achọrọ SRF maka igosipụta mkpụrụ ndụ ihe eji eme ihe yana plastik synaptik mana ọ bụghị maka nlanarị ọhụụ (Ramanan et al., ). Site na ntụgharị uche ya nke ngosipụta na ọrụ nke ihe nchebe metụtara cytoskeletal, SRF yiri ka ọ bụ nke na-agbanwe ọrụ synaptik n'ime mgbanwe nhazi nke sistemu na seraronal (Knöll na Nordheim, ), na -eme ka ọ bụrụ onye ọkpụkpọ nwere ike ịrụ ọrụ na-adabere n'ụkpụrụ nkwụghachi ụgwọ nke na-akpata mgbanwe na-akpata nrụgide na circuitry. N’ezie, SRF na abata na NAc nke nnagide oji site na nchekari onodu ojoo nke na adighi ala ala, o wee kegide ya FosB onye na - akwalite ma na - abawanye usoro nke usoro ihe ndabere (Vialou et al., ). Igwe ntinye obi dabere na ntinye nke ΔFosB bu ihe di nkpa maka ihe nnabata, ma odi iche na ntinye nke ΔFosB dika ihe eji eme ya. FosB onye na-akwalite (Vialou et al., , ).

Ntinye uto uto nke uto-1 (Egr-1)

Egr-1, makwaara dị ka zinc mkpịsị mkpụrụ protein 268, bụ ntinye ntinye neuronal na-ejikọ DNA site na akara mkpịsị aka zinc dị iche. O yiri ka ọ na-ekere òkè na plasticity neuronal (Knapska na Kaczmarek, ), ikekwe site na nhazi ya maka ngosipụta nke synaptobrevin II (Petersohn na Thiel, ). Egr-1 na-abata na hippocampus site na oke nrụgide, dị ka igwuri egwu na oke, site na mmegharị nke usoro epigenetic dị mgbagwoju anya na-agbanye site na nkwalite hipcoampal glucocorticoid receptor (GR) (achịkọtara na Reul, ). MAPK na-edenye ala nke GRs na-eme ka ọrụ MSK1 na Elk-1 rụọ ọrụ, ụzọ na-agbadata CREB na c-fos induction. Nke a kwadoro Ser10 phosphorylation na Lys14 acetylation nke histone 3 na onye na-akwalite gene Erg-1, na-eduga na mkpakọ chromatin dị jụụ, mgbanwe na DNA methylation, na ngosipụta Erg-1 (Gutièrrez-Mecinas et al., ; Saunderson et al., ). Mmetụta a dịkarịa ala ụbọchị ụbụrụ, ọ nwere ike ịbụ ihe kpatara azịza ndị ọzọ na-esochi igwu mmiri, ikekwe na-akpata nchekasị na-akpata ogologo oge, njirimara nke nsogbu mgbanwe ọnọdụ. N'ezie, ngosi Egr-1 belatara na hippocampus na PFC site na mwepụ mmekọrịta ọha na eze (Ieraci et al., ), na-egosi na ọ nwere ike itinye aka na mgbanwe ogologo oge na ọnọdụ n'ihi nrụgide ogologo. N’ọdịnihu, ọ ga-adị mkpa iji chọpụta ma mmetụta Egr-1 nkwupụta na hippocampus sitere na mgbanwe nke usoro nlegharị anya nke hippocampal na ma ọ bụ site na mmegharị sekit ndị ọzọ, dị ka NAc.

Egr-3, nke jikọtara Egr-1 ma mekwaa ka ọ dabere na ọrụ dabere na arụ ọrụ, etinyela nso nso a n'ọtụtụ nsogbu ọnọdụ uche. Egr-3 ọtụtụ ebumnuche gụnyere Arc (Li et al., ), tụlere n'okpuru, yana NMDA na GABA nnabata subunits (Roberts et al., ; Kim et al., ), na-atụ aro na ọ nwere ike itinye aka na ego iwepụ / inhibitory n'ụdị ụgwọ ọrụ. Ihe omumu mbu site na iji SNPs na Egr-3 gene choputara nmekorita nke puru iche na nsogbu oria aru nke umuaka (Gallitano et al., ). Ọmụmụ ihe na-adịbeghị anya jiri data microarray buru ibu ma chọpụta na Erg-3 nwere ike ịrụ ọrụ dị oke mkpa na dysregulation nke netwọọdụ transperent PFC na ndị ọrịa nwere nkụda mmụọ (Pfaffenseller et al., ). Ọzọkwa, ọmụmụ siri ike na-atụ aro na Egr-3 nwere ike mebepụta ụfọdụ nsonaazụ nke clozapine n'ịgwọ ma psychosis na ihe mgbaàmà ọria abụọ (Gallitano-Mendel et al., ; Williams et al., ), na-atụ aro na inwekwu ọmụmụ Egr-3 nwere ike ịnye nghọta dị omimi na etiology nke nsogbu ọnọdụ.

NPAS4

4 protein PR ngalaba protein, ma ọ bụ NPAS4, bụ ihe ntụgharị-arụ ọrụ na-adabere n'ọrụ neurons. Ọ dị mkpa maka mmepe nke intneurons inhibitory yana plastik neuronal na nzaghachi na ahụmịhe (Lin et al., ; Ploski et al., ; Ramamoorthi et al., ; Sim et al., ). Ebe ọ bụ na NPAS4 na-abanye na ma ọ bụrụ na ọ na - eme ihe ọgbụgba dị iche iche na - egbochi ma na - ebido oghere dị iche na ụdị sel ọ bụla (Spiegel et al., ), a na-eche na ọ ga-ahazi njikwa obi ụtọ na inhibitory n'ime sekit (Bloodgood et al., ). Ebumnuche amata nke NPAS4 gụnyere ụbụrụ neurotrophic na-akpata (BDNF) na neurons excitatory, yana FERM na PDZ nwere protein 3 (Frmpd3) na inhibitory neurons (Spiegel et al., ).

Na HPC, NPAS4 nbanye site na ma usoro ọgbụgba synaptik na usoro nkụda mmụọ chọrọ ụzọ MAPK na PI3K (Coba et al., ), na-atụ aro ka otu njikọ rụọ ọrụ maka ndị ọzọ IEGs, dịka CREB. Nchekasị na-eme ka NPAS4 rụọ ọrụ na-agbasa ozi ozugbo, dịka agonist na-ekekọta glucocorticoid receptor na-ejikọ onye na-akwalite NPAS4 iji wedata okwu ya n'oge oke nrụgide (Furukawa-Hibi et al., ). Mgbe nrụgide na-adịghị ala ala, NPAS4 mRNA belatara nke ọma na hippocampus nke ụmụ oke, na ụmụ obere NPAS4 ndị a na - adịghị ike etolite etolite etolite etolite etolite etolite (Ibi et al., ; Yun et al., ; Coutellier et al., ). Mgbanwe ndị a nwere ogologo oge nwere ike ibilite site na nhazi iwu, dịka onye na-akwalite NPAS4 nwere ọtụtụ agwaetiti CpG, nrụgide na-amụba methylation na saịtị ndị a (Furukawa-Hibi et al., ). Ọtụtụ ụdị anụmanụ, gụnyere agịga akara SERT na ụzọ Flinders Sensitive Line, egosila mmekọrịta dị n'etiti nkwupụta NPAS4 dị ala, akparamagwa omume na-akpata nkụda mmụọ, na nguzogide antidepressant (Guidotti et al., ; Bigio et al., ). Emeela ọtụtụ ọrụ a na HPC, a chọkwuru ọmụmụ ihe iji kọwaa ọrụ NPAS4 na NAc na mpaghara ndị ọzọ na-akwụghachi ụgwọ na gburugburu nke otu ụdị ịda mba ahụ. Ọzọkwa, NPAS4 ka akwadoro na NAc mgbe ekpughere ọgwụ ọjọọ nke mmekpa ahụ (Guo et al., ), mana ọ bụ ihe omume na azịza ọgwụ ma ọ bụ omume na-akpata iri ahụ riri ahụ.

Nchịkwa metụtara protein cytokeleton (Arc)

Arc bụ protein na-agbanwe agbanwe, na-agbanwe agbanwe, multidomain nke na-emekọrịta ọtụtụ ndị mmekọ (Myrum et al., ; Zhang et al., ). Site na mmekorita ndị a, Arc na-arụ ọrụ iji nọgide na-enwe phosphorylation nke actin depolymerization factor cofilin, na-echekwa ụdị adịghị arụ ọrụ ya, ma si otú ahụ kwadoro polymerization nke actin (Messaoudi et al., ). N'ụzọ dị otú a, Arc na-akwalite ntinye nke spines dị mkpa, dendritic dendritic dị mkpụmkpụ, ọrụ na-eso ΔFosB (lee n'elu). Ihe di nkpa, Arc bu kwa uzo banyere postsynaptik ebe o na aru oru di nkpa na ntinye ndi nnabata AMPA (Chowdhury et al., ) ma na-akwalite nguzobe spines dendritic akabeghị aka (Peebles et al., ) na ịda mba ogologo oge (LTD; Bramham et al., ).

Ihe akaebe n’oge na-adịbeghị anya na-egosi na ike igosipụta okwu Arc na ọrụ ya na ọtụtụ akụkụ nke ịda mba. N'ihe dị iche iche nke oke oke na òké, Arc na-ebute mmiri ara na cortex na hippocampus site na nnukwu nrụgide, mana enwere ike ịnwe ma ọ bụ na-achịkwa ya site na nrụgide na-adịghị ala ala dabere na paradaịs (Elizalde et al., ; Molteni et al., ; Boulle et al., ). Na mgbakwunye, imirikiti ọmụmụ na-ekwu na ọgwụgwọ antidepressant na-adịghị ala ala na-akpata echiche Arc n'oge mkpokọ cortex na hippocampus, na nrụgide Arc na-akpata nchekasị na mpaghara ụbụrụ a kapịrị ọnụ na-ekwupụta nsonaazụ na-esote nrụgide na ọrụ ọgụgụ isi (nke a chịkọtara na Li et al. , ). Ya mere, odi ka enwere ike nsogbu ma obu ntinye nke arc nwere ike idi nkpa maka imeghari udiri nsogbu nke syryps, ikekwe na ntinye glutamatergic na NAc ma obu njikọta n’etiti ngalaba cortical na basal-ganglia, ma agha agha kari ichoputa ihe ntinye aka na ngosipụta nke Arc na nzaghachi nrụgide na nsogbu ọnọdụ.

Homer1a

Ihe nchebe Homer1 na-eme ihe dị ka nhịahụ na-emegharị mmekọrịta na ọnọdụ nke ihe nchebe neuronal ndị ọzọ, gụnyere ndị na-anabata metabotropic glutamate (dịka, mGluR1 na mGluR5), IP3 ndị na-anabata, Shank, na ndị ọzọ. Thedị dị mkpirikpi dị iche iche nke Homer1, Homer1a, na-ebute ọrụ neuronal ma na-eme dị ka ihe na-adịghị mma iji gbochie mmekọrịta dị iche iche ogologo oge, Homer1b na Homer1c na ntanetị nkịtị ha site na asọmpi maka saịtị njikọ njikọ EVH1. Iji maa atụ, Homer1a egosiputala ndị na-anabata mGluR nnata ozi sitere na mgbada agbada (Tu et al., ) na-ebute mbelata nha na nha nke dendritic spines (Sala et al., ) site na mgbochi nke Shank ezubere ka synapses. Na Homer1 a na-egosi mkpụrụ ndụ ihe ọmụmụ pathogenesis nke nnukwu ịda mbà n'obi site na njikọta nke mkpụrụ ndụ yana yana ọmụmụ neuroimaging (Rietschel et al., ). Na usoro mmụba ugboro ugboro nke adịghị mma nke ịda mbà n'obi, a na-ebelata Homer1a na cortex, nke a na-agbanwegharị site na ikpughe antidepressant (Sun et al., ). N'ụzọ na-akpali mmasị, a na-abanye na Homer1b na 1c na HPC site na nrụgide mmeri mmadụ (Wagner et al., ), na ịbawanye elu na ọkwa ha na Homer1a nwere ike rụọ ọrụ dị ka usoro nke nnabata. Nke a bụ n'ihi na okebiga ahụhụ nke Homer1a na òké HPC na-akwalite nrụgide na nrụgide mmeri nke ọha mmadụ, na ụmụ anụmanụ karịrị akarị na-egosi enweghị nchekwube akparamagwa na omume ịnagide omume dị ala (Wagner et al., ). N'ime ngụkọ, a na-eme ka Homer1a na antipsychotics nke na-eme ndị na-anabata dopamine (enyocha ya na Iasevoli et al., ), mana ọrụ ọ bụla nke Homer1a na nzaghachi omume omume ngọngọ na nrụgide na ọgwụ nke mmegbu ka ga-ekpughe.

Ajuju di iche na uzo ozo n’abia

N'agbanyeghi otutu ihe akaebe nke ntinye aka nke IEG n'ime uzo di iche iche na ndi ozo nwere nsogbu obi, anyi amatabeghi onyinye nke IEG iji nye ugwo oru na omume ndi ozo. Nzọụkwụ dị oke mkpa bụ ịchọta IEGs na mpaghara ikuku kpọmkwem. Zọ dị otú a siri ike site na iji usoro oge gboo, mana ọganiihu na nso nso a maka ịkọ aha mkpụrụ ndụ yana njigide mkpụrụ ndụ na njikọta sekit na-enye ụzọ dị egwu iji zaa ụfọdụ ajụjụ pụrụ iche dị mkpa.

Enwere ọrụ dị iche iche maka IEGs n'otu ụdị neuronal ụfọdụ?

Ndi IEGs na-arụ otu ọrụ na ụdị sel akwara niile? N'ihi na ụfọdụ ntụgharị uche na-emetụta ndị ọzọ (dịka, NPAS4), ịdị mkpa nke ngosipụta IEG na nsogbu ọnọdụ nwere ike kegide ha na ntinye ọnụ ọgụgụ ụmụ amaala. Ahịrị ntụpọ transgenic nke na-enye ohere nhọrọ ma ọ bụ ịkụ aka nke IEGs na neurons nke na-ewepụta kpọmkwem neurotransmitters (ya bụ, DAT-Cre ma ọ bụ GAD-Cre) ma ọ bụ gosipụta ndị nnabata kpọmkwem (ya bụ, D1-Cre ma ọ bụ D2-Cre) ga-abụ ngwá ọrụ dị mkpa na ọmụmụ n'ọdịnihu. . Na mgbakwunye, ijikọ eriri ndị a na Via-based viral vector ga-eleba ọrụ dị iche iche nke IEGs anya na mpaghara nke neuronal n'otu n'otu.

Kedu ọrụ IEGs na mpaghara ụbụrụ nwere kpọmkwem?

Ọ bụ ezie na enwere ike ịgbalite IEGs n'ọtụtụ ụbụrụ na mmeghachi omume na nrụgide ma ọ bụ ọgwụ, adịghị mkpa nghọta ha dị na sekit na-akpata ihe riri ahụ na omume ịda mbà. Inyocha ntinye nke ime mmiri IEG arụ ọrụ n'ime mesolimbic na cortical circuitry na arụmọrụ cell na akparamagwa ụmụ anụmanụ, usoro akụrụngwa ịba amụ ga-adị oke mkpa. Iji maa atụ, site na ijikọta nje virus nke na-ekwupụta Cre injection dị ka NAc na mpaghara na-ekwupụta nje overrexpressing IEG nwere mmasị n'ụdị nke dabere na Mmanụ a gbanyere na HPC, mmadụ nwere ike ịlele nsonaazụ nke IEG na ọrụ ahụ. nke HPC neurons na-enwete NAc kpọmkwem, yana omume anụmanụ na-esote (ọgụgụ (Figure3A) .3A). N’aka ozo, site na ijikọta ngosipụta nlọghachi azụ nke enzyme Cas9 na ngosipụta nke ime obodo RNA, enwere ike iji CRISPR nke na-atụgharị uche nke IEG iji chọpụta ọrụ dị iche iche dị na ya (ọgụgụ. (Figure3B), 3B), ịbịakwute ugbu a ka ndị otu anyị na ndị ọzọ na-akụ. N'ezie, usoro ndị a nwere ike jikọtara na usoro ịkwọ ụgbọala transgenic Cre nke akọwapụtara n’elu iji kwe ka ụdị sel na Nchịkọta usoro nke IEGs, usoro dị mkpa maka nghọta anyị banyere ọrụ ha na pathophysiology nke ọrịa psychiatric.

Nyocha 3  

Zọ enwere ike maka ịgba ajụjụ ọnụ gbasara ajụjụ ole IEG. (A) Ihe ngosiputa gosiputara oria ojoo a na aru mmadu dika NAc ya na oria nke gosiputara IEG n'uzo nke dabere ...

Gịnị bụ ebumnuche mkpụrụ ndụ nke IEGs nwere ụdị sel na sekit dị iche iche?

Ọ bụ ezie na ọ dị mkpa ịghọta ọrụ nke IEGs n'ụdị sel ụfọdụ, mkpokọta neuronal, na sekit ndị akọwapụtara, ọtụtụ ndị IEG na-eme atụmatụ ọgwụ na-agaghị ekwe omume maka ọgwụgwọ nke ọrịa psychiatric, ebe ha na-arụ ọrụ dị oke mkpa na mpaghara ụbụrụ na-enweghị ọrịa na mpaghara ndị ọzọ. anụ ahụ. Agbanyeghị, ikpughe ebumpụta ụwa nke ebumnuche nke ntụgharị IEG, dịka ihe nchebe ezinụlọ Fos ma ọ bụ NPAS4, nwere ike ikpughere ndị mgbasa ozi dị oke egwu nke ọrịa pathophysiology nke nwere ike ịdabere na ọ ga-eme ka ọ dị mma. Ọganiihu ọhụụ na ngosipụta nke mkpụrụ ndụ, dịka ịsụgharị ribosomal metụtara ịdị ọcha (TRAP; Heiman et al., ), enwere ike mgbanwe na ike siri ike ka etinyere na Cre-dependral cell- na usoro nso-nsoro akọwapụtara n’elu (Lobo, ; McCullough et al., ), maka iji rụọ ọrụ esonye na usoro esiri ike (Sakurai et al., ). Iji akara kọmpụta ndị na-adabere na Creation na-ekwupụta ribosomes nke GFP jikọtara ya na nje virus retrograde Cre ga-eme ka TRAP na-akọwa ihe ngosipụta nke usoro mkpụrụ ndụ (ọgụgụ. (Figure3C) .3C). Bjikọta usoro dị otu a na ụmụ oke akpọrọ maka IEG akọwapụtara ga-ahapụ inye ntule nke ntinye aka nke IEG na nkwupụta usoro mkpụrụedemede akọwapụtara nke ọma n'ọnọdụ nrụgide ma ọ bụ ọgwụ. Anyị na-ebu amụma na usoro ndị dị otú a ga-ekpughere ngwaahịa mkpụrụ ndụ ihe omimi na-akpata ọnọdụ ma ọ bụ nsogbu nke iji ihe nwere ike ịbụ ọgwụ ga-aga nke ọgwụgwọ ọhụụ.

Mkpebi

O doro anya na ikpughe ihe omume ndị na-akpata nchekasị na ndụ na-eme ka nsogbu ghara ịba uru, ma ọtụtụ ọmụmụ na ịkọwapụta postmortem chịkọtara ebe a na-atụ aro na nke a nwere ike ibilite na akụkụ nke nrụgide nrụpụta nrụpụta ngagharị ngagharị nke ngosipụta IEG. Maka ụfọdụ IEGs ndị a, dịka CREB, Homer1a, na ΔFosB, ihe akaebe bara ụba maka ọrụ ha na mmeghachi omume nrụgide, ọtụtụ akụkụ nke ọgba aghara ọnọdụ, ihe riri ahụ ọgwụ ọjọọ, na ọbụna ọgwụgwọ antidepressant, ihe ịma aka a dị ugbu a na ijikọta ọrụ ha n'ofe ụbụrụ. na ụdị mkpụrụ ndụ gụnyere na ịchọpụta ebumnuche ha dị n'okpuru ala iji kpughee ndị ha ga-achọ ọgwụ ọhụụ. Maka ndị ọzọ IEGs, dịka Egr-1, NPAS4, na Arc, ntinye ha site na nrụgide na-eme ka ha nwee mmetụta dị omimi na nchọpụta nsogbu mgbanwe ọnọdụ, mana a chọpụtabeghị njikọ njikọta na omume metụtara ịda mbà n'obi, ma gaa n'ihu na-amụ ọrụ ha na ịrụ ọrụ elegharị anya dị mkpa. N'okwu niile, ọ bịara doo anya na idozigharị nrụgide nke sekọndị ụgwọ ọrụ, na ntinye nke glutamatergic ka ọ bụrụ NAc, bụ ihe dị oke mkpa na mmepe nke ịda mba-na ihe ndị metụtara mmụọ, yana IEGs na-arụ ọrụ dị mkpa na Usoro a ma nwee ike ịnye ụzọ, usoro ekwentị na usoro nke usoro nsogbu ọgbụgba na - etolite etolite na usoro ọgwụgwọ.

Onye nyere onyinye

CM, EW, na AR nyocha, wee dee ma dezie ihe odide ahụ.

ego

Ego ndi oru a sitere na onyinye sitere n'aka AR si na National Institute of Mental Health (1R01MH111604-01) na Whitehall Foundation (2013-08-43).

Nkwupụta mgbasa ozi mkparịta ụka

Ndị na-ede akwụkwọ na-ekwupụta na e mere nchọpụta ahụ na enweghi mmekọrịta ọ bụla ma ọ bụ ego ma ọ bụ ego nke a pụrụ iwere dị ka ihe nwere ike ịmasị.

Notes

Ego (na) enyemaka a kwadoro akwụkwọ a:

National Institute of Health Mental10.13039/100000025 1R01MH111604-01.
Whitehall Foundation10.13039/100001391 2013-08-43.

References

  • Alberini CM (2009). Ihe ntụgharị na ebe nchekwa ogologo oge na plastic synaptik. Fisiol. Rev. 89, 121 – 145. 10.1152 / physrev.00017.2008 [PMC free article] [PubMed] [Cross Ref]
  • Ambroggi F., Ishikawa A., Fields HL, Nicola SM (2008). Basolateral amygdala neurons na-eme ka omume na-achọ ụgwọ ọrụ site na ntanetị na-eme ọfụma na-eme ka akwara ndị dịrị uru. Neuron 59, 648 – 661. 10.1016 / j.neuron.2008.07.004 [PMC free article] [PubMed] [Cross Ref]
  • Andersson M., Westin JE, Cenci MA (2003). Oge nke atFosB na-adọ adọ dị ka immunoreactivity na ọkwa prodynorphin mRNA mgbe ọ kwụsịrị ọgwụgwọ dopaminomimetic na-adịghị ala ala. Eur. J. Neurosci. 17, 661 – 666. 10.1046 / j.1460-9568.2003.02469.x [PubMed] [Cross Ref]
  • Barrot M., Olivier JD, Perrotti LI, DiLeone RJ, Berton O., Eisch AJ, et al. . (2002). Ọrụ CREB n’ime akwara na-eme ka a mata ihe omume mmeghachi omume na-akpali akpali. Proc. Natl. Acad. Sci. USA 99, 11435 – 11440. 10.1073 / pnas.172091899 [PMC free article] [PubMed] [Cross Ref]
  • Barrot M., Wallace DL, Bolanos CA, Graham DL, Perrotti LI, Neve RL, et al. . (2005). Nchịkwa nke ụjọ na mbido omume mmekọahụ site na CREB na ngwongwo akwara. Proc. Natl. Acad. Sci. USA 102, 8357 – 8362. 10.1073 / pnas.0500587102 [PMC free article] [PubMed] [Cross Ref]
  • Berridge KC, Kringelbach ML (2015). Ụtọ usoro na ụbụrụ. Neuron 86, 646-664. 10.1016 / j.neuron.2015.02.018 [PMC free article] [PubMed] [Cross Ref]
  • Bigio B., Mathe AA, Sousa VC, Zelli D., Svenningsson P., McEwen BS, et al. . (2016). Epigenetics na ume na ventral hippocampus na-emezi ihe ngwa ngwa antidepressant: Ihe ndị metụtara nguzogide ọgwụgwọ. Proc. Natl. Acad. Sci. USA 113, 7906 – 7911. 10.1073 / pnas.1603111113 [PMC free article] [PubMed] [Cross Ref]
  • Björkholm C., Monteggia LM (2016). BDNF - isi ihe ntụgharị nke mmetụta antidepressant. Neuropharmacology 102, 72-79. Nke 10.1016 / j.neuropharm.2015.10.034 [PMC free article] [PubMed] [Cross Ref]
  • Bloodgood BL, Sharma N., Browne HA, Trepman AZ, Greenberg ME (2013). NPAS4 ntụgharị-arụ ọrụ na-arụ ọrụ na-achịkwa ihe mgbochi naanị ngalaba. Nature 503, 121 – 125. 10.1038 / nature12743 [PMC free article] [PubMed] [Cross Ref]
  • Bortolato B., Carvalho AF, McIntyre RS (2014). Ọkpụkpụ ụbụrụ na nnukwu nkụda mmụọ: nyocha nke ụlọ nyocha ihe osise. CNS Neurol. Nkewa. Ebumnuche Ọgwụ Ọjọọ 13, 1804 – 1818. 10.2174 / 1871527313666141130203823 [PubMed] [Cross Ref]
  • Boulle F., Massart R., Stragier E., Paizanis E., Zaidan L., Marday S., et al. . (2014). Hippocampal na omume dysfunctions na usoro nke òké nke nrụgide gburugburu ebe obibi: normalization site agomelatine. Ntụgharị. Psychiatry 4, e485. 10.1038 / tp.2014.125 [PMC free article] [PubMed] [Cross Ref]
  • Bramham CR, Alme MN, Bittins M., Kuipers SD, Nair RR, Pai B., et al. . (2010). Akụ nke ncheta synaptik. .Chụ. Resbụrụ Res. 200, 125 – 140. 10.1007 / s00221-009-1959-2 [PMC free article] [PubMed] [Cross Ref]
  • Carle TL, Ohnishi YN, Ohnishi YH, Alibhai IN, Wilkinson MB, Kumar A., ​​et al. . (2007). Aszọ nchekwa nchekwa na njikwa ike maka mbibi FosB: njirimara nke ngalaba FosB degron yana ihe ọ pụtara maka nkwụsi ike ΔFosB. Eur. J. Neurosci. 25, 3009 – 3019. 10.1111 / j.1460-9568.2007.05575.x [PubMed] [Cross Ref]
  • Carlezon WA, Jr., Duman RS, Nestler EJ (2005). Ọtụtụ ihu nke CREB. Neurosci Trends. 28, 436 – 445. 10.1016 / j.tins.2005.06.005 [PubMed] [Cross Ref]
  • Chen AC, Shirayama Y., Shin KH, Neve RL, Duman RS (2001). Nkọwapụta mmeghachi nke mmeghachi omume cAMP na-ejikọ protein (CREB) na hippocampus na-arụpụta ọgwụ antidepressant. Biol. Psychiatry 49, 753 – 762. 10.1016 / S0006-3223 (00) 01114-8 [PubMed] [Cross Ref]
  • Chowdhury S., Onye Ọzụzụ Atụrụ JD, Okuno H., Lyford G., Petralia RS, Plath N., et al. . (2006). Arc / Arg3.1 na-arụ ọrụ na igwe endocytic iji mezie azụmaahịa nnabata nke AMPA. Neuron 52, 445 – 459. 10.1016 / j.neuron.2006.08.033 [PMC free article] [PubMed] [Cross Ref]
  • Christoffel DJ, Golden SA, Dumitriu D., Robison AJ, Janssen WG, Ahn HF, et al. . (2011). IkappaB kinase na-achịkwa mmerị nrụgide nke nrụgide na-akpata mmekọrịta na plasticity omume. J. Neurosci. 31, 314 – 321. 10.1523 / JNEUROSCI.4763-10.2011 [PMC free article] [PubMed] [Cross Ref]
  • Chrivia JC, Kwok RP, Lamb N., Hagiwara M., Montminy MR, Goodman RH (1993). Phosphorylated CREB na-ejikọ kpọmkwem na CBP protein nuklia. Nature 365, 855 – 859. 10.1038 / 365855a0 [PubMed] [Cross Ref]
  • Coba MP, Valor LM, Kopanitsa MV, Afinowi OWO, Grant SG (2008). Netiwọki Kinase jikọtara profaịlụ nke N-methyl-D-aspartate receptor-mediate gene gene dị na hippoftọs. J. Biol. Chem. 283, 34101 – 34107. 10.1074 / jbc.M804951200 [PMC free article] [PubMed] [Cross Ref]
  • Conti AC, Cryan JF, Dalvi A., Lucki I., Blendy JA (2002). CAMP mmeghachi nke mmeghachi ahụ protein dị mkpa maka mmụba nke ihe metụtara neurotrophic sitere na ụbụrụ, mana ọbụghị omume ma ọ bụ nzaghachi endocrine na ọgwụ antidepressant. J. Neurosci. 22, 3262 – 3268. [PubMed]
  • Coutellier L., Gilbert V., Shepard R. (2015). Npas4 erughi ihe na-eme ka ihe ojoo diri umuaka. Behav. Resbụrụ Res. 295, 17 – 25. 10.1016 / j.bbr.2015.04.027 [PubMed] [Cross Ref]
  • Covington HE, III., Maze I., Sun H., Bomze HM, DeMaio KD, Wu EY, et al. . (2011). Otu ọrụ maka nrụgide akuko na - eme ka nsogbu na - emetụta nrụgide. Neuron 71, 656 – 670. 10.1016 / j.neuron.2011.06.007 [PMC free article] [PubMed] [Cross Ref]
  • Cruz FC, Javier Rubio F., Oche BT (2015). Iji c-fos iji muo ihe banyere neuronal ensemble na corticostriatal circuitry nke riri ahu. Resbụrụ Res. 1628, 157 – 173. 10.1016 / j.brainres.2014.11.005 [PMC free article] [PubMed] [Cross Ref]
  • Dalton VS, Kolshus E., McLoughlin DM (2014). Epigenetics na ịda mba: nlọghachi nke ndị a tara ahụhụ. J. Afọ. Nkewa. 155, 1 – 12. 10.1016 / j.jad.2013.10.028 [PubMed] [Cross Ref]
  • Dash PK, Hochner B., Kandel ER (1990). Ntinye nke mmeghachi omume nke CAMP n'ime akwara nke Aplysia sensory neurons na-egbochi mmezi ogologo oge. Nature 345, 718 – 721. 10.1038 / 345718a0 [PubMed] [Cross Ref]
  • Dobrazanski P., Noguchi T., Kovary K., Rizzo CA, Lazo PS, Bravo R. (1991). Ngwa ahịa abụọ nke fosB gene, FosB na mpempe ya dị mkpirikpi, FosB / SF, bụ ndị na-emegharị transbetal na fibroblasts. Mol. Ala. Biol. 11, 5470 – 5478. 10.1128 / MCB.11.11.5470 [PMC free article] [PubMed] [Cross Ref]
  • Donahue RJ, Muschamp JW, Russo SJ, Nestler EJ, Carlezon WA, Jr. (2014). Mmetụta nke eserese ΔFosB na-emebiga ihe ókè na ketamine na mmekọrịta mmadụ ibe ya na-akpata nrụgide anhedonia na ụmụ oke. Biol. Psychiatry 76, 550 – 558. 10.1016 / j.biopsych.2013.12.014 [PMC free article] [PubMed] [Cross Ref]
  • Duman RS (2004). Ọnọdụ obi ụfụ: okwu banyere ndụ neuronal na ọnwụ? Biol. Psychiatry 56, 140 – 145. 10.1016 / j.biopsych.2004.02.033 [PubMed] [Cross Ref]
  • Eagle AL, Gajewski PA, Yang M., Kechner ME, Al Masraf BS, Kennedy PJ, et al. . (2015). Ahụmịhe dabere na ntinye uche nke pocFosB na-achịkwa mmụta. J. Neurosci. 35, 13773 – 13783. 10.1523 / JNEUROSCI.2083-15.2015 [PubMed] [Cross Ref]
  • Elizalde N., pastọ PM, Garcia-Garcia AL, Serres F., Venzala E., Huarte J., et al. . (2010). Iwu nke akara nrịbama nke ụdị synaptik na ụdị nke ịda mba: nrụgide na-adịghị ala ala na ngosipụta mbelata nke VGLUT1. J. Neurochem. 114, 1302 – 1314. 10.1111 / j.1471-4159.2010.06854.x [PubMed] [Cross Ref]
  • Fanselow MS (2000). Egwu a na-atụgharị uche na ya, ihe ncheta mmegharị ahụ, na hippotampus. Behav. Resbụrụ Res. 110, 73 – 81. 10.1016 / S0166-4328 (99) 00186-2 [PubMed] [Cross Ref]
  • Ferrara P., Andermarcher E., Bossis G., Acquaviva C., Brockly F., Jariel-Encontre I., et al. . (2003). Ebumnuche nke ihe owuwu nke na-akpata c-Fos protein proteasomal protein ịkpa ike na-emetụta iche na ọnọdụ nke ngosipụta. Oncogene 22, 1461 – 1474. 10.1038 / sj.onc.1206266 [PubMed] [Cross Ref]
  • Floresco SB (2015). Ngwurugwu akwara na - agakọ: nnabata n'etiti cognition, mmetụta na ime ihe. Kwa Afọ. Rev. Psychol. 66, 25 – 52. 10.1146 / annurev-psych-010213-115159 [PubMed] [Cross Ref]
  • Furukawa-Hibi Y., Nagai T., Yun J., Yamada K. (2015). Nchegbu na-abawanye methylation DNA nke ngalaba PAS ngalaba 4 (Npas4) neuronal. Neuroreport 26, 827 – 832. 10.1097 / WNR.0000000000000430 [PubMed] [Cross Ref]
  • Furukawa-Hibi Y., Yun J., Nagai T., Yamada K. (2012). Mgbachi transcriptional nke neuronal PAS ngalaba 4 (Npas4) site na nrụgide site na ijikọ nnabata glucocorticoid agonist na onye na-akwalite ya. J. Neurochem. 123, 866 – 875. 10.1111 / jnc.12034 [PubMed] [Cross Ref]
  • Gallitano AL, Tillman R., Dinu V., Geller B. (2012). Ọmụmụ ihe gbasara ezinaụlọ nke nzụlite izizi nke mkpụrụ ndụ 3 ya na ọrịa ihe imetụtara nwatakịrị. J. Afọ. Nkewa. 138, 387 – 396. 10.1016 / j.jad.2012.01.011 [PMC free article] [PubMed] [Cross Ref]
  • Gallitano-Mendel A., Wozniak DF, Pehek EA, Milbrandt J. (2008). Mmụ oke na - ezighi ezi ntinye dịka Egr3 na - azaghachi nsonaazụ mgbochi nke clozapine ma na - eguzogide nsogbu ya. Neuropsychopharmacology 33, 1266 – 1275. 10.1038 / sj.npp.1301505 [PMC free article] [PubMed] [Cross Ref]
  • Geaghan M., Cairns MJ (2015). MicroRNA na dysregulation posttranscriptional na psychiatry. Biol. Psychiatry 78, 231 – 239. 10.1016 / j.biopsych.2014.12.009 [PubMed] [Cross Ref]
  • Gruber AJ, Hussain RJ, O'Donnell P. (2009). Ngwurugwu na-abawanye: ngbanwe maka omume na-eduzi ihe mgbaru ọsọ. Ejiri otu 4: e5062. 10.1371 / akwụkwọ akụkọ.pone.0005062 [PMC free article] [PubMed] [Cross Ref]
  • Grueter BA, Robison AJ, Neve RL, Nestler EJ, Malenka RC (2013). FosB dị iche na emeghari akwara dị iche iche na - arụ ọrụ na - arụ ọrụ na ụzọ na - adịghị mma. Proc. Natl. Acad. Sci. USA 110, 1923 – 1928. 10.1073 / pnas.1221742110 [PMC free article] [PubMed] [Cross Ref]
  • Guidotti G., Calabrese F., Auletta F., Olivier J., Racagni G., Homberg J., et al. . (2012). Mmetụta mmepe nke onye na-ebugharị serotonin na ngosipụta nke npas4 na akara GABAergic: mgbanwe site na ọgwụgwọ antidepressant. Neuropsychopharmacology 37, 746 – 758. 10.1038 / npp.2011.252 [PMC free article] [PubMed] [Cross Ref]
  • Guo ML, Xue B., Jin DZ, Liu ZG, Fibuch EE, Mao LM, et al. . (2012). Nkwalite nke nkwuputa protein Npas4 site na nchịkwa na-adịghị ala ala nke amphetamine na oke nucleus accumbens na vivo. Neurosci. Hapụ. 528, 210 – 214. 10.1016 / j.neulet.2012.07.048 [PMC free article] [PubMed] [Cross Ref]
  • Gutièrrez-Mecinas M., Trollope AF, Collins A., Morfett H., Hesketh SA, Kersante F., et al. . (2011). Mmeghachi omume omume ogologo oge na-akpata nchekasị gụnyere mkparịta ụka nke ndị na-anabata glucocorticoid na akara mgbaàmà ERK1 / 2-MSK1-Elk-1. Proc. Natl. Acad. Sci. USA 108, 13806 – 13811. 10.1073 / pnas.1104383108 [PMC free article] [PubMed] [Cross Ref]
  • Heiman M., Kulicke R., Fenster RJ, Greengard P., Heintz N. (2014). Dị sel na - arụ ọrụ mRNA kapịrị ọnụ site n'ịsụgharị ribosome purfinity purfinity (TRAP). Nat. Protoc. 9, 1282 – 1291. 10.1038 / nprot.2014.085 [PMC free article] [PubMed] [Cross Ref]
  • Olile anya BT, Nye HE, Kelz MB, Self DW, Iadarola MJ, Nakabeppu Y., et al. . (1994). Ntinye nke usoro AP-1 dị ogologo nke nwere ihe nchekwa Fos-nke gbanwere na ụbụrụ site na cocaine na-adịghị ala ala na ọgwụgwọ ndị ọzọ na-adịghị ala ala. Neuron 13, 1235 – 1244. 10.1016 / 0896-6273 (94) 90061-2 [PubMed] [Cross Ref]
  • Iasevoli F., Tomasetti C., Ambesi-Impiombato A., Muscettola G., de Bartolomeis A. (2009). Dopamine na-anabata nnabata ga - enye onyinye na Homer1a induction: nghọta n'ime ihe ndị dị na antipsychotic molekụla. Prog. Neuropsychopharmacol. Biol. Psychiatry 33, 813 – 821. 10.1016 / j.pnpbp.2009.02.009 [PubMed] [Cross Ref]
  • Ibi D., Takuma K., Koike H., Mizoguchi H., Tsuritani K., Kuwahara Y., et al. . (2008). Mmebi nke mmekọrịta mmadụ na ibe ya bụ mmebi nke akwara hippocampal bụ ihe ejikọtara ya na ebe nchekwa na omume metụtara mmụọ na ụmụ oke. J. Neurochem. 105, 921 – 932. 10.1111 / j.1471-4159.2007.05207.x [PubMed] [Cross Ref]
  • Ieraci A., Mallei A., Popoli M. (2016). Nchekasị nke mmekọrịta mmadụ na ibe ya na-akpata nchekasị-dịka akparamaagwa na mgbanwe nke mkpụrụ ndụ ihe metụtara akwara ozi metụtara ụmụ nwoke ụmụ nwoke. Osisi Neural. 2016: 6212983. 10.1155 / 2016 / 6212983 [PMC free article] [PubMed] [Cross Ref]
  • Janak PH, Tye KM (2015). Site na sekit rue omume amygdala. Nature 517, 284 – 292. 10.1038 / nature14188 [PMC free article] [PubMed] [Cross Ref]
  • Kalivas PW, Volkow N., Seamans J. (2005). Ebumnuche na-enweghị nchịkwa na iri mmadụ ahụ: ọnụọgụ nje na nnyefe glutamate prefrontal-accumbens. Neuron 45, 647 – 650. 10.1016 / j.neuron.2005.02.005 [PubMed] [Cross Ref]
  • Kandel ER (2012). Ọmụmụ ihe banyere ndụ nke ebe nchekwa: cAMP, PKA, CRE, CREB-1, CREB-2, na CPEB. Mol. Xbụrụ 5: 14. 10.1186 / 1756-6606-5-14 [PMC free article] [PubMed] [Cross Ref]
  • Kanoski SE, Grill HJ (2017). Hippocampus na-enye aka na nchịkwa nri: mnemonic, neuroanatomical, na usoro endocrine. Biol. Psychiatry 81, 748 – 756. 10.1016 / j.biopsych.2015.09.011 [PMC free article] [PubMed] [Cross Ref]
  • Kida S., Serita T. (2014). Ọrụ CREB dị ka onye na-achịkwa nke ọma na nhazi na nkwalite ncheta. Resbụrụ Res. Bull 105, 17 – 24. 10.1016 / j.brainresbull.2014.04.011 [PubMed] [Cross Ref]
  • Kim JH, Roberts DS, Hu Y., Lau GC, Brooks-Kayal AR, Farb DH, et al. . (2012). Ihe neurotrophic nke sitere na Brain na-eji CREB na Egr3 hazie ọkwa NMDA na-anabata ọnụnọ nertron. J. Neurochem. 120, 210 – 219. 10.1111 / j.1471-4159.2011.07555.x [PMC free article] [PubMed] [Cross Ref]
  • Knapska E., Kaczmarek L. (2004). Onyinye maka plasticity nke neuronal na ụbụrụ mammalian: Zif268 / Egr-1 / NGFI-A / Krox-24 / TIS8 / ZENK? Prog. Neurobiol. 74, 183 – 211. 10.1016 / j.pneurobio.2004.05.007 [PubMed] [Cross Ref]
  • Knöll B., Nordheim A. (2009). Versrụ ọrụ nke ihe ndị na - eme ka mmadụ mepe emepe na akwara ozi: pardigm nke SRF. Neurosci Trends. 32, 432 – 442. 10.1016 / j.tins.2009.05.004 [PubMed] [Cross Ref]
  • Kovács KJ (1998). c-Fos dị ka ihe ntụgharị: echiche na-akpata nrụgide (re) site na maapụ ọrụ. Neurochem. Int. 33, 287 – 297. 10.1016 / S0197-0186 (98) 00023-0 [PubMed] [Cross Ref]
  • Kovács KJ (1998). Nyocha nyocha c-Fos dị ka ihe ntụgharị: echiche na-akpata nchekasị (re) site na maapụ ọrụ. Neurochem. Int. 33, 287 – 297. 10.1016 / S0197-0186 (98) 00023-0 [PubMed] [Cross Ref]
  • Lammel S., Tye KM, Warden MR (2014). Ọganiru na nghota nsogbu ọnọdụ: optogenetic dissection nke akụkụ okirikiri. Genes Brain Behav. 13, 38 – 51. 10.1111 / gbb.12049 [PubMed] [Cross Ref]
  • Li L., Carter J., Gao X., Whitehead J., Tourtellotte WG (2005). Ihe ntanetị metụtara neuroplasticity bụ akara ebumnuche nke ebumnuche mmalite uto (Egr) ihe ntụgharị. Mol. Cell Biol. 25, 10286 – 10300. 10.1128 / MCB.25.23.10286-10300.2005 [PMC free article] [PubMed] [Cross Ref]
  • Li Y., Pehrson AL, Waller JA, Dale E., Sanchez C., Gulinello M. (2015). Nnyocha dị oke mkpa nke protein metụtara njikọ cytoskeleton (Arc / Arg3.1) na-etinye aka na ịchịkwa plasticity dendritic, usoro ntụgharị uche, na ọnọdụ n'ụdị anụmanụ nke ịda mba. N'ihu. Neurosci. 9: 279 10.3389 / fnins.2015.00279PMC free article] [PubMed] [Cross Ref]
  • Lin Y., Bloodgood BL, Hauser JL, Lapan AD, Koon AC, Kim TK, et al. . (2008). Iwu dabere n'ọrụ nke inhibitory synapse development site na Npas4. Nature 455, 1198 – 1204. 10.1038 / nature07319 [PMC free article] [PubMed] [Cross Ref]
  • Lobo MK (2009). Mgbasa echiche molecular nke striatonigral na striatopallidal ọkara spiny neurons gara aga, ugbu a, na ọdịnihu. Int. Rev. Neurobiol. 89, 1 – 35. 10.1016 / S0074-7742 (09) 89001-6 [PubMed] [Cross Ref]
  • Lobo MK, Zaman S., Damez-Werno DM, Koo JW, Bagot RC, DiNieri JA, et al. . (2013). ΔFosB induction na transatal ọkara spiny neuron subtypes na nzaghachi ọgwụ na-adịghị ala ala, mmetụta uche, na mkpali nke optogenetic. J. Neurosci. 33, 18381 – 18395. 10.1523 / JNEUROSCI.1875-13.2013 [PMC free article] [PubMed] [Cross Ref]
  • Luking KR, Pagliaccio D., Luby JL, Barch DM (2016). Nkwụghachi ụgwọ ụgwọ yana ihe egwu maka nkụda mmụọ n'ofe mmepe. Trends Cogn. Sci. 20, 456 – 468. 10.1016 / j.tics.2016.04.002 [PMC free article] [PubMed] [Cross Ref]
  • Maze I., Covington HE, III., Dietz DM, LaPlant Q., Renthal W., Russo SJ, et al. . (2010). Ọrụ dị mkpa nke histone methyltransferase G9a na plasticity na-akpata. Sayensị 327, 213 – 216. 10.1126 / sayensị.1179438 [PMC free article] [PubMed] [Cross Ref]
  • McCullough KM, Morrison FG, Ressler KJ (2016). Rid mechi oghere ahụ, chee ihu ụdị mkpụrụ ndụ ga - agaghari nke njikọta akwara ozi gbasara egwu. Neurobiol. Mụta. Isi. 135, 27 – 39. 10.1016 / j.nlm.2016.07.025 [PMC free article] [PubMed] [Cross Ref]
  • Messaoudi E., Kanhema T., Soulé J., Tiron A., Dagyte G., da Silva B., et al. . (2007). Nchịkọta Arc / Arg3.1 na-ejikọ aka na njikwa ike ogologo oge site na nhazi nke polymerization mpaghara na dentate gyrus. na vivo. J. Neurosci. 27, 10445 – 10455. 10.1523 / JNEUROSCI.2883-07.2007 [PubMed] [Cross Ref]
  • Molteni R., Calabrese F., Chourbaji S., Brandwein C., Racagni G., Gass P., et al. . (2010). Mké nkụda mmụọ na-egosipụta nke ukwuu na a na-egosipụta njikwa glucocorticoid na-egosipụta nrụgide na-adabere na nrụgide nke ụbụrụ neurotrophic na protein na-ejikọtakwa cytoskeleton. J. Psychopharmacol. 24, 595 – 603. 10.1177 / 0269881108099815 [PubMed] [Cross Ref]
  • Muschamp JW, Nemeth CL, Robison AJ, Nestler EJ, Carlezon WA, Jr. (2012). ΔFosB na-eme ka mmetụta cocaine na-akwụghachi ụgwọ ma na -ebelata mmetụta pro-depression nke kappa-opioid receptor agonist U50488. Biol. Psychiatry 71, 44 – 50. 10.1016 / j.biopsych.2011.08.011 [PMC free article] [PubMed] [Cross Ref]
  • Myrum C., Baumann A., Bustad HJ, Flydal MI, Mariaule V., Alvira S., et al. . (2015). Arc bụ protein na-agbanwe agbanwe nke nwere ike ịgbanwegharị nke nwere ike ịgbanwe ọrụ onwe ya. Bioko. J. 468, 145 – 158. 10.1042 / BJ20141446 [PMC free article] [PubMed] [Cross Ref]
  • Nestler EJ (2015a). Ọrụ nke ụgwọ ọrụ ụgwọ ọrụ nke ụbụrụ na ịda mbà n'obi: usoro ntụgharị. Int. Rev. Neurobiol. 124, 151–170. Nke a: 10.1016 / bs.irn.2015.07.003 [PMC free article] [PubMed] [Cross Ref]
  • Nestler EJ (2015b). FosB: onye na - achịkwa ntụgharị nke nrụgide na mmeghachi omume antidepressant. Eur. J. Pharmacol. 753, 66 – 72. 10.1016 / j.ejphar.2014.10.034 [PMC free article] [PubMed] [Cross Ref]
  • Nestler EJ, Hyman SE, Holtzman DM, Malenka RC (2015). Molecular Neuropharmacology: Ntọala maka Clinical Neuroscience, 3rd Edn. Columbus, OH: McGraw-Hill Education, 528.
  • Nestler EJ, Kelz MB, Chen J. (1999). ΔFosB: onye n’enweta ihe omuma nke ogologo oge ihe gbasara aru na ihe gbasara agwa. Resbụrụ Res. 835, 10 – 17. 10.1016 / S0006-8993 (98) 01191-3 [PubMed] [Cross Ref]
  • Newton SS, Thome J., Wallace TL, Shirayama Y., Schlesinger L., Sakai N., et al. . (2002). Mgbochi nke mmeghachi omume mmeghachi omume nke cAMP ma ọ bụ dynorphin na ngwongwo akwara na-eme ka mmetụta antidepressant yiri. J. Neurosci. 22, 10883 – 10890. [PubMed]
  • Nibuya M., Morinobu S., Duman RS (1995). Iwu nchịkwa nke BDNF na trkB mRNA na ụbụrụ oke site na njiri ọgwụ electroconvulsive na-adịghị ala ala na ọgwụgwọ ọgwụ antidepressant. J. Neurosci. 15, 7539 – 7547. [PubMed]
  • Nibuya M., Nestler EJ, Duman RS (1996). Nlekọta ọgwụ mgbochi na-adịghị ala ala na-eme ka ngosipụta nke mmeghachi omume cAMP na-ejikọ protein (CREB) na oke oke hippocampus. J. Neurosci. 16, 2365 – 2372. [PubMed]
  • Peebles CL, Yoo J., Thwin MT, Palop JJ, Noebels JL, Finkbeiner S. (2010). Arc na-achịkwa akwara ozi ma na-ekwusi ike netwọọdụ na vivo. Proc. Natl. Acad. Sci. USA 107, 18173 – 18178. 10.1073 / pnas.1006546107 [PMC free article] [PubMed] [Cross Ref]
  • Perrotti LI, Hadeishi Y., Ulery PG, Barrot M., Monteggia L., Duman RS, et al. . (2004). Induction nke ΔFosB na ụbụrụ metụtara ụgwọ ọrụ mgbe ọ nwesịrị nrụgide na-adịghị ala ala. J. Neurosci. 24, 10594 – 10602. 10.1523 / JNEUROSCI.2542-04.2004 [PubMed] [Cross Ref]
  • Petersohn D., Thiel G. (1996). Ọrụ nke zinc-mkpịsị aka na-echebe Sp1 na zif268 / egr-1 na ntụgharị iwu nke usoro mmadụ synaptobrevin II. Eur. J. Biochem. 239, 827 – 834. 10.1111 / j.1432-1033.1996.0827u.x [PubMed] [Cross Ref]
  • Pfaffenseller B., da Silva Magalhaes PV, De Bastiani MA, Castro MA, Gallitano AL, Kapczinski F., et al. . (2016). Ngosiputa di iche nke ogha n’usoro ihe nlegha anya na pre ቅድመalal cortex nke ndi oria nwere oria obi na agha: ikike di na nzaghachi mbido mbu nke 3. Ntụgharị. Psychiatry 6, e805. 10.1038 / tp.2016.78 [PMC free article] [PubMed] [Cross Ref]
  • Pliakas AM, Carlson RR, Neve RL, Konradi C., Nestler EJ, Carlezon WA, Jr. (2001). Gbanwee mmeghachi omume nke cocaine na ụba enweghi ike na nnwale mmiri a na-amanye jikọtara ya na nkwupụta ụda protein cAMP dị elu na njikwa protein. J. Neurosci. 21, 7397 – 7403. [PMC free article] [PubMed]
  • Ploski JE, Monsey MS, Nguyen T., DiLeone RJ, Schafe GE (2011). A chọrọ protein 4 (Npas4) nke neuronal pas maka ncheta ncheta ọhụụ ma na-emegharị ahụ. PLoS ONE 6: e23760. 10.1371 / journal.pone.0023760 [PMC free article] [PubMed] [Cross Ref]
  • Ramamoorthi K., Fropf R., Belfort GM, Fitzmaurice HL, McKinney RM, Neve RL, et al. . (2011). Npas4 na-ahazi usoro ntụgharị okwu na CA3 achọrọ maka ntọala ebe nchekwa. Sayensị 334, 1669 – 1675. 10.1126 / sayensị.1208049 [PMC free article] [PubMed] [Cross Ref]
  • Ramanan N., Shen Y., Sarsfield S., Lemberger T., Schutz G., Linden DJ, et al. (2005). SRF na-emegharị usoro ngosipụta mkpụrụ ndụ ihe mepụtara na plasta synaptik mana enweghị usoro neuronal. Nat. Neurosci. 8, 759 – 767. 10.1038 / nn1462 [PubMed] [Cross Ref]
  • Reul JM (2014). Ime ncheta nke ihe ndị na - akpata obi erughị ala: njem na - eme njem, inyefe mkpụrụ ndụ ihe na - edenye ụzọ. Ihu ihu. XLUX psychiatry: 5. 5 / fpsyt.10.3389 [PMC free article] [PubMed] [Cross Ref]
  • Rietschel M., Mattheisen M., Frank J., Treutlein J., Degenhardt F., Breuer R., et al. . (2010). Mkpakọrịta Genome dum, mmepụtaghachi- na ọmụmụ ihe gbasara neuromosis gosipụtara HOMER1 na etiology nke nnukwu ịda mba. Biol. Psychiatry 68, 578 – 585. 10.1016 / j.biopsych.2010.05.038 [PubMed] [Cross Ref]
  • Roberts DS, Raol YH, Bandyopadhyay S., Lund IV, Budreck EC, Passini MA, et al. . (2005). Ihe mkpalite Egr3 nke onye na-akwalite GABRA4 dị ka usoro maka ijikwa usoro nchịkwa nke GABA (A) nnabata okwu subunit na-anabata ihe. Proc. Natl. Acad. Sci. USA 4, 102 – 11894. 11899 / pnas.10.1073 [PMC free article] [PubMed] [Cross Ref]
  • Robinson TE, Kolb B. (1999). Mgbanwe na morphology nke dendrites na dendritic spines na nucleus accumbens na prefrontal cortex na-esochi ugboro ugboro na amphetamine ma ọ bụ cocaine. Eur. J. Neurosci. 11, 1598 – 1604. 10.1046 / j.1460-9568.1999.00576.x [PubMed] [Cross Ref]
  • Robison AJ, Vialou V., Sun H.-S., Labonte B., Golden SA, Dias C., et al. . (2014). Fluoxetine na-agbanwe onye na-akwalite CaMKIIα na nucleus accumbens iji mezie njikọ ΔFosB na antidepressant mmetụta. Neuropsychopharmacology 39, 1178 – 1186. 10.1038 / npp.2013.319 [PMC free article] [PubMed] [Cross Ref]
  • Russo SJ, Nestler EJ (2013). Thebụrụ na-akwụghachi ụdọ circuit na nsogbu ọgba aghara. Nat. Rev. Neurosci. 14, 609 – 625. 10.1038 / nrn3381 [PMC free article] [PubMed] [Cross Ref]
  • Russo SJ, Dietz DM, Dumitriu D., Morrison JH, Malenka RC, Nestler EJ (2010). Nazọ synapse ahụ riri ahụ: usoro nke synaptik na plasticity nke nhazi ihe na nucleus accumbens. Neurosci Trends. 33, 267 – 276. 10.1016 / j.tins.2010.02.002 [PMC free article] [PubMed] [Cross Ref]
  • Sakurai K., Zhao S., Takatoh J., Rodriguez E., Lu J., Leavitt AD, et al. . (2016). Nwetakwa ma chịkwaa ya na ngalaba akpọrọ neuronal na ngalaba akpọrọ CANE na-akọwapụta usoro egwu mmadụ. Neuron 92, 739 – 753. 10.1016 / j.neuron.2016.10.015 [PMC free article] [PubMed] [Cross Ref]
  • Sala C., Futai K., Yamamoto K., Worley PF, Hayashi Y., Sheng M. (2003). Mgbochi nke dendritic spaine morphogenesis na mbufụt synaptik site na protein-inducible protein Homer1a. J. Neurosci. 23, 6327 – 6337. [PubMed]
  • Saunderson EA, Spiers H., Mifsud KR, Gutierrez-Mecinas M., Trollope AF, Shaikh A., et al. . (2016). Ngosiputa mkpalite mkpalite na omume sitere na DNA methylation na onyinye methyl na dentate gyrus. Proc. Natl. Acad. Sci. USA 113, 4830 – 4835. 10.1073 / pnas.1524857113 [PMC free article] [PubMed] [Cross Ref]
  • Sesack SR, Grace AA (2010). Cortico-basal ganglia na-akwụghachi ụgwọ netwọkụ: microcircuitry. Neuropsychopharmacology 35, 27 – 47. 10.1038 / npp.2009.93 [PMC free article] [PubMed] [Cross Ref]
  • Sheng M., Greenberg ME (1990). Iwu na ọrụ nke c-fos na mkpụrụ ndụ ihe nketa ndị ọzọ ozugbo na usoro ụjọ. Neuron 4, 477 – 485. 10.1016 / 0896-6273 (90) 90106-P [PubMed] [Cross Ref]
  • Sim SY, Antolin S., Lin CW, Lin YX, Lois C. (2013). Mmụba excitability cell na - akpata mkpịsị synaptik na neurons ọhụrụ na gyrus okenye dentate nke chọrọ Npas4. J. Neurosci. 33, 7928 – 7940. 10.1523 / JNEUROSCI.1571-12.2013 [PMC free article] [PubMed] [Cross Ref]
  • Spiegel I., Mardinly AR, Gabel HW, Bazinet JE, Couch CH, Tzeng CP, et al. . (2014). Npas4 na-achịkwa nguzozi-inhibitory inititory na sekọnkụ akwara site na mmemme mkpụrụ ndụ ihe-otu. 157 Cell, 1216 – 1229. 10.1016 / j.cell.2014.03.058 [PMC free article] [PubMed] [Cross Ref]
  • Stuber GD, Sparta DR, Stamatakis AM, van Leeuwen WA, Hardjoprajitno JE, Cho S., et al. . (2011). Nzipu nke sitere na amygdala rue akwara na - eme ka a na-achọ ụgwọ ọrụ. Nature 475, 377 – 380. 10.1038 / nature10194 [PMC free article] [PubMed] [Cross Ref]
  • Sun P., Wang F., Wang L., Zhang Y., Yamamoto R., Sugai T., et al. . (2011). Mmụba nke cortical pyramidal cell excitability na-esochi ịda mbà n'obi-dị ka omume na ụmụ oke: ọmụmụ mkpali transcranial magnetik. J. Neurosci. 31, 16464 – 16472. 10.1523 / JNEUROSCI.1542-11.2011 [PubMed] [Cross Ref]
  • Surmeier DJ, Ding J., Day M., Wang Z., Shen W. (2007). D1 na D2 dopamine-receptor modulation nke straatal glutamatergic akara na striatal ọkara spiny neurons. Neurosci Trends. 30, 228 – 235. 10.1016 / j.tins.2007.03.008 [PubMed] [Cross Ref]
  • Thome J., Sakai N., Shin K., Steffen C., Zhang YJ, Impey S., et al. . (2000). Ọkpụkpọ cAMP mmeghachi nke mkpụrụedemede nke mkpụrụedemede na-agbanwe site na ọgwụgwọ ọgwụ na-egbu mgbu. J. Neurosci. 20, 4030 – 4036. [PubMed]
  • Tu JC, Xiao B., Yuan JP, Lanahan AA, Leoffert K., Li M., et al. . (1998). Homer na-ejikọ ụkpụrụ ohuru nke akụkọ ọhụrụ na ihe jikọrọ 1 metabotropic glutamate receiptors na ndị na-anabata IP3. Neuron 21, 717 – 726. 10.1016 / S0896-6273 (00) 80589-9 [PubMed] [Cross Ref]
  • Ulery PG, Rudenko G., Nestler EJ (2006). Iwu nke stabilityFosB kwụsie ike site na iji phosphorylation. J. Neurosci. 26, 5131 – 5142. 10.1523 / JNEUROSCI.4970-05.2006 [PubMed] [Cross Ref]
  • Ulery-Reynolds PG, Castillo MA, Vialou V., Russo SJ, Nestler EJ (2009). Phosphorylation nke ΔFosB na-eme ka mkpebi ya guzosie ike na vivo. Neuroscience 158, 369 – 372. 10.1016 / j.neuroscience.2008.10.059 [PMC free article] [PubMed] [Cross Ref]
  • Vezina P., Giovino AA, Wisdom RA, Stewart J. (1989). Nlebara anya na gburugburu ebe obibi n'etiti ihe na-eme ka ihe na-emetụta morphine na amphetamine. Pharmacol. Bioko. Behav. 32, 581 – 584. 10.1016 / 0091-3057 (89) 90201-3 [PubMed] [Cross Ref]
  • Vialou V., Bagot RC, Cahill ME, Ferguson D., Robison AJ, Dietz DM, et al. . (2014). Circule cortical Prefrontal maka ịda mba- na omume metụtara nchegbu bụ nke cholecystokinin bụ ọrụ nke ΔFosB. J. Neurosci. 34, 3878 – 3887. 10.1523 / JNEUROSCI.1787-13.2014 [PMC free article] [PubMed] [Cross Ref]
  • Vialou V., Feng J., Robison AJ, Ku SM, Ferguson D., Scobie KN, et al. . (2012). Ihe nzaghachi serum na ihe nzaghachi CAMP na-ejikọ protein na achọrọ maka ịbanye na cocaine nke ΔFosB. J. Neurosci. 32, 7577 – 7584. 10.1523 / JNEUROSCI.1381-12.2012 [PMC free article] [PubMed] [Cross Ref]
  • Vialou V., Maze I., Renthal W., LaPlant QC, Watts EL, Mouzon E., et al. . (2010b). Ihe nzaghachi Serum na-akwalite iguzogide nrụgide mmekọrịta na-adịghị ala ala site na ntinye nke ΔFosB. J. Neurosci. 30, 14585 – 14592. 10.1523 / JNEUROSCI.2496-10.2010 [PMC free article] [PubMed] [Cross Ref]
  • Vialou V., Robison AJ, Laplant QC, Covington HE, III., Dietz DM, Ohnishi YN, et al. . (2010a). ΔFosB na ụbụrụ ụgwọ ọrụ na-eme ka mmiri ghara ịdị na nchekasị na mmeghachi omume antidepressant. Nat. Neurosci. 13, 745 – 752. 10.1038 / nn.2551 [PMC free article] [PubMed] [Cross Ref]
  • Vialou V., Thibault M., Kaska S., Cooper S., Gajewski P., Eagle A., et al. . (2015). Ihe dị iche na ntinye nke FosB na-anọpụ iche na ụbụrụ niile site na fluoxetine na nrụgide na-adịghị ala ala. Neuropharmacology 99, 28 – 37. 10.1016 / j.neuropharm.2015.07.005 [PMC free article] [PubMed] [Cross Ref]
  • Wagner KV, Hartmann J., Labermaier C., Hausl AS, Zhao G., Harbich D., et al. . (2015). Ọrụ Homer1 / mGluR5 na-agbanwe ngwangwa na nrụgide mmekọrịta na-adịghị ala ala. Neuropsychopharmacology 40, 1222 – 1233. 10.1038 / npp.2014.308 [PMC free article] [PubMed] [Cross Ref]
  • Wallace DL, Han MH, Graham DL, Green TA, Vialou V., Iniguez SD, et al. . (2009). Iwu CREB nke nucleus na-egbochi ọnụnọ mmadụ na-ebute enweghị ike na akparamagwa omume. Nat. Neurosci. 12, 200 – 209. 10.1038 / nn.2257 [PMC free article] [PubMed] [Cross Ref]
  • West AE, Greenberg ME (2011). Ọrụ akwara ozi- mepụtara mkpụrụ ndụ ihe nrịba ama nke usoro synapse na ọrụ ọgụgụ isi. Igwe Mmiri Oyi. Nkwanye Anya. Biol. 3: a005744. 10.1101 / cshperspect.a005744 [PMC free article] [PubMed] [Cross Ref]
  • Williams AA, Ingram WM, Levine S., Resnik J., Kamel CM, Lish JR, et al. . (2012). Mbelata nke serotonin 2A ndị na-anabata ndị na-eguzosi ike n'ihe nke Egr3-ụmụ irighiri akwara na mbelata locomotor site na clozapine. Neuropsychopharmacology 37, 2285 – 2298. 10.1038 / npp.2012.81 [PMC free article] [PubMed] [Cross Ref]
  • Yin JC, Wallach JS, Del Vecchio M., Wilder EL, Zhou H., Quinn WG, et al. . (1994). Induction nke ajọ ihe CREB transgene na-egbochi icheta ogologo oge na Drosophila. 79 Cell, 49 – 58. 10.1016 / 0092-8674 (94) 90399-9 [PubMed] [Cross Ref]
  • Yun J., Koike H., Ibi D., Toth E., Mizoguchi H., Nitta A., et al. . (2010). Ihe mgbochi na-adịghị ala ala na-egbochi neurogenesis na ncheta ụjọ nke hippocampus na ụmụ oke: ntinye aka ga - ekwe omume nke ihe ntụgharị kpọmkwem nke ụbụrụ Npas4. J. Neurochem. 114, 1840 – 1851. 10.1111 / j.1471-4159.2010.06893.x [PubMed] [Cross Ref]
  • Zhang W., Wu J., Ward MD, Yang S., Chuang YA, Xiao M., et al. . (2015). Ihe ndabere nke arc na-egbochi protein synaptik: nsonaazụ nke ọrịa cognitive. Neuron 86, 490 – 500. 10.1016 / j.neuron.2015.03.030 [PMC free article] [PubMed] [Cross Ref]