DeltaFosB: Ọnụ Ụzọ Mbata na Mkpụrụ Ntugharị Na-eme Ihe n'ime Nkọwa Na-eme Ka Adumbens? (2006)

The Journal of Neuroscience, 15 November 2006, 26(46): 11809-11810; doi: 10.1523 / JNEUROSCI.4135-06.2006

A na-ahụta nucleus accumbens (NAc) dị ka njikọ dị n'etiti sistemụ limbic na moto (Mogenson et al., 1980) na ndabere nke ntinye glutamatergic convergent ya sitere na ọtụtụ akụkụ cortical limbic, dị ka cortex prefrontal, yana nsonaazụ ya na akụkụ ndị metụtara njikwa moto, dị ka pallidum. NAc na-enwetakwa nnukwu innergic dopaminergic site na mpaghara ventral tegmental site na ụzọ mesolimbic nke na-etinye aka na usoro metụtara ụgwọ ọrụ na riri ahụ. N'ime NAc, ntinye dopaminergic na glutamatergic nwere ike imekọrịta iji chịkwaa omume ebumnuche ebumnuche (nzaghachi-usoro nsonaazụ) nke ụgwọ ọrụ sitere n'okike (nri, mmiri, mmekọahụ) ma ọ bụ ọgwụ ọjọọ, yana ihe mkpali metụtara ha.

Mkpughe ọgwụ ugboro ugboro na-ebute mgbanwe mkpụrụ ndụ ogologo oge na mkpụrụ ndụ n'ime NAc nke a na-eche na ọ ga-enye aka na omume mkpasu iwe ogologo oge metụtara riri ahụ. N'ime mgbanwe ndị dị otú ahụ, ntinye nke ihe ntụgharị ΔFosB n'ime dynorphin-positive media spiny neurons bụ nnukwu mmasị. ΔFosB abụrụla onye na-ahụ maka ntụgharị ederede na-adịte aka na-adịgide adịgide gosipụtara na ọ na-etinye aka na usoro plastik jikọtara ya na mgbanwe na-eri ahụ. N'ezie, ọ na-agbanwe mmetụta na-akwụghachi ụgwọ na mkpali nke cocaine ma jikọta ya na nnabata na mmetụta nke opiates. Agbanyeghị, ruo taa, amachaghị banyere ọrụ ΔFosB na mgbanwe nke omume sitere na ụgwọ ọrụ eke.

N'ime akụkọ ha bipụtara na nso nso a Journal of Neuroscience, Olausson et al. jiri nlezianya zaa ajụjụ a site n'igosipụta na nkwubi okwu nke ΔFosB na-enwe ike ma na-abawanye, n'otu n'otu, ma inweta ihe nkwado ngwá ọrụ maka, na mkpali iji nweta, nri.

Olausson et al. buru ụzọ nyochaa mmetụta nke injections ugboro ugboro, n'okpuru ọnọdụ ndị a maara na-ebute ΔFosB, nke ọgwụ ise dị iche iche: cocaine, nicotine, (+) - 3,4-methylenedioxymethamphetamine (MDMA), na amphetamine, na inweta nke ntanye ntanye maka pellets nri na. oke erighi nri. Ewezuga MDMA, usoro ọgwụgwọ niile butere mmetuta omume na ha niile mụbara ma ọnụ ọgụgụ mpịazi na-arụsi ọrụ ike nke oke oke na-ebupụta n'oge nhazi akụrụngwa.Olausson et al. (2006), ha Fig. 1 (http://www.jneurosci.org/cgi/content/full/26/36/9196/F1)] na mkpali iji nweta nri dị ka atụpụtara site na mmụba na-agbaji na nhazi usoro na-aga n'ihu (PR) [Olausson et al. (2006), Fig. 2B (http://www.jneurosci.org/cgi/content/full/26/36/9196/F2)). Ya mere, ọgwụgwọ a maara na-ebute ΔFosB na NAc nwere ike ịbawanye nzaghachi ngwa ngwa maka nri. Olausson et al. wee nwaa igosi mmekọrịta dị n'etiti okwu NAc nke ΔFosB na mkpali a na-ahụ anya maka nri. Maka nke a, ha jiri ụdị abụọ nke ntinye aka nke ΔFosB na NAc. Ha buru ụzọ mụọ ụmụ oke NSE-tTA-TetOP-ΔFosB transgenic, nke na-egosipụta protein naanị na neurons dynorphin-positive nke striatal complex mgbe ewepụrụ doxycycline (mgbanwe molekụla nke na-egbochi ọrụ nkwalite TA).Fig. 1A). Ụmụ oke ndị a gosipụtara ΔFosB ọ bụghị naanị na NAc kamakwa na dorsal striatum, nke na-etinye aka na mmụta omume (Mee et al., 2004) (ya bụ, usoro nzaghachi mkpali na-akpaghị aka bụ nke enweghị uche maka mbelata ụgwọ ọrụ). Ndị ode akwụkwọ si otú a kpalitere nkwubi okwu nke ΔFosB na isi nke NAc site na iji mbufe nje na-ebute nje na oke. N'ime nnwale abụọ a, okwu artificial nke ΔFosB ṅomiri mmetụta dị ike nke ikpughe ọgwụ ugboro ugboro na ma nnweta nke nzaghachi ngwá ọrụ.Olausson et al. (2006), fig ha. 3 (http://www.jneurosci.org/cgi/content/full/26/36/9196/F3) na 5 (http://www.jneurosci.org/cgi/content/full/26/36/9196/F5)] na mkpali maka nri [Olausson et al. (2006), fig ha. 4A (http://www.jneurosci.org/cgi/content/full/26/36/9196/F4) na 7 (http://www.jneurosci.org/cgi/content/full/26/36/9196/F7)] (Fig. 1B). Otú ọ dị, ọ gbanweeghị mkpali iji nweta nri n'okpuru ad libitum ọnọdụ, na-atụ aro na a na-ekpughe phenotype a na-ahụ anya naanị mgbe anụmanụ chere ihe ịma aka omume ihu, nke egosila na ọ dabere na neurons dopaminergic na-atụpụta na NAc.Salamone et al., 1994).

 

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Ngosipụta nke ΔFosB na nucleus accumbens na-abawanye nzaghachi ngwa maka nri na ụmụ oke na oke: nghọta ọhụrụ maka echiche gating nke dopamine? A, Nlereanya nnwale. Anụmanụ nchịkwa (n'aka ekpe) bụ ụmụ oke NSE-tTA-TetOP-ΔFosB bitransgenic nyere doxycycline (Dox) ma ọ bụ oke ejiri LacZ-cDNA nwere nje virus. Ha abụọ ekwupụtaghị ΔFosB. Right, Bitransgenic NSE-tTA-TetOP-ΔFosB ụmụ oke napụrụ na doxycycline gosipụtara ΔFosB na mgbagwoju anya, ebe oke na-agbanye n'ime isi nke NAc na ΔFosB -cDNA nwere nje herpes gosipụtara ΔFosB kpọmkwem na nhazi a. B, Nchịkọta nke nsonaazụ ya. Mgbe a na-ama aka inweta ihe mkpuchi ngwá ọrụ (IC) (ya bụ, ịpị ọkpọ iji nweta nri) ma ọ bụ n'oge PR, ụmụ anụmanụ na-emebiga ihe ókè ΔFosB gosipụtara nzaghachi ngwa ngwa ma e jiri ya tụnyere ụmụ anụmanụ na-achịkwa. BP, ebe mgbawa. C, Echiche echiche. N'okpuru ọnọdụ nkịtị (aka ekpe), omume nke anụmanụ gosipụtara na-eche ihe ịma aka iji nweta ụgwọ ọrụ na-achịkwa ma ọ bụrụ na ọ dị n'etiti omume ya na ihe ga-esi na ya pụta, yana uru mkpali nke ụgwọ ọrụ ahụ. N'ime NAc, dopamine nwere ike ijikwa windo na-arụ ọrụ nke a ga-ahọrọ nzaghachi omume kwesịrị ekwesị maka ebumnuche mkpali. Mgbe ΔFosB karịrị akarị (n'aka nri), windo a ga-agbasawanye, nke a ga-enye aka na nzaghachi omume siri ike maka otu mkpali mkpali.

Mmetụta ndị ahụ achọpụtara abụghị ihe kpatara mmụba na-enweghị isi, n'ihi na n'ime nnwale niile akụrụngwa nzaghachi nke oke na oke na-eduzi naanị na manipulandum nọ n'ọrụ. Ọzọkwa, o yighị ka nzaghachi ngwa ngwa a na-eme ka a na-ahụ na nyocha abụọ ahụ sitere na mmụta ΔFosB na-akpata, n'ihi na (1) akara ngosi nke ụmụ oke transgenic na-egosipụta ΔFosB na PR nwere mmetụta nke satiety-induced enhancer devaluation, na (2) ọbụlagodi na oke oke oke oke nke ΔFosB gbasoro ọzụzụ akụrụngwa, si otú a na-egbochi mmekọrịta ọ bụla n'etiti oke ngosipụta na ọzụzụ, ọ mụbara mkpali iji nweta nri n'oge PR na-esote.

Nsonaazụ ndị a gosipụtara n'ụzọ doro anya na oke oke nke ΔFosB na NAc na-eme ka ịzaghachi ngwa ngwa ma na-abawanye mkpali maka nri (Fig. 1B). A na-atụ aro ΔFosB ka ọ bụrụ ngbanwe mkpụrụ ndụ nkịtị na-etinye aka na mgbanwe nke akụkụ mkpali nke omume eduzi ebumnuche. O doro anya na ihe ngosi a bụ isi ihe dị mkpa na nghọta nke usoro metụtara ụgwọ ọrụ, nke n'ihi ya na-atụ aro ajụjụ ndị na-adọrọ mmasị maka nyocha ndị ọzọ.

Nsonaazụ nke Olausson et al. dabere na ntinye nke ΔFosB na NAc site na ntụtụ ọgwụ na-abụghị nke ndị na-eme nnwale na-enyefe ma ọ bụ na-emebiga ihe ókè, ma na-ekwu naanị omume ebumnuche ebumnuche maka nri. Nzọụkwụ ọzọ ga-abụ iji lebara ọrụ ΔFosB anya n'ihe gbasara ịchọ ọgwụ ike. N'ezie, mgbe ahụ riri ahụ malitere, a na-eduzi omume mmanye naanị maka ọgwụ ahụ, ebe a na-eleghara ụgwọ ọrụ eke dị ka nri anya. Ọ ga-abụ ihe dị oke mkpa iji chọpụta, mgbe mmepe nke ịchọ ọgwụ na-amanye (mmanye).Vanderschuren na Everitt, 2005), ma ΔFosB na-ebute na NAc ma ọ bụ n'akụkụ akụkụ azụ nke striatum, na-etinye aka na omume ndị na-adịghị agbanwe agbanwe na ma ọ na-ejikọta ya na nkwalite ma ọ bụ belata mkpali maka ụgwọ ọrụ eke. Echiche nke abụọ nke enwere ike iburu n'uche na nyocha n'ọdịnihu na-adabere na ngosipụta na NAC neuronal subpopulations dị iche iche na-aza kpọmkwem ụgwọ ọrụ dị iche iche n'oge omume ọrụ (Carelli et al., 2000). N'ihi na ọ dị ka ọ gaghị ekwe omume na injections na-enweghị atụ na-enyefe ma ọ bụ nkwubi okwu nke ΔFosB nwere ike ịkọ maka nzaghachi neuronal a kapịrị ọnụ, a ga-enyocha okwu netwọk nke ΔFosB nke ọma. N'ezie, ọ bụrụ na ejiri ọgwụ onwe onye na-agbatị ogologo oge jikọtara ya na ntinye nke ΔFosB na NAC subnetwork na-emeghachi omume na-akpali akpali maka ọgwụ ọjọọ, mmeghachi omume omume maka ọgwụ ọjọọ, na naanị maka ọgwụ ọjọọ, na-emebi ụgwọ ọrụ eke dị ka nri ga-atụ anya. Ya mere, dabere na ugbu a, nsonaazụ na-akpali akpali, ọ dị mkpa ugbu a iji ụdị anụmanụ dị ugbu a nke ịchọ ọgwụ ọjọọ, dabere na nchịkwa onwe onye na-adịghị ala ala. N'ụzọ dị otú a, anyị nwere ike nweta nghọta ọzọ banyere ọrụ ΔFosB na mmepe nke omume ịchọ ọgwụ ọjọọ na-emerụ ahụ nke ịchọ ụgwọ ọrụ sitere n'okike nke yiri ka ọ dị ntakịrị ọnụ na ndị riri ahụ.Usoro nyocha na nyocha akụkọ nke Mkpụrụ uche uche IVR).

N'ọkwa usoro mmụta karịa, nsonaazụ ndị a kwekọrọ na echiche gating nke ọrụ dopamine (Grace, 2000). Enwere ike ịtụ aro na, n'ime NAc, ΔFosB nwere ike gbasaa windo ọrụ nke njikwa site na dopamine nke mmepụta omume na-eduzi ebumnuche na nzaghachi nke ihe mkpali dị egwu (Fig. 1C). Enwere ike ịrụ ụka na, ọbụlagodi na-enweghị uru mkpali dị elu, otu ihe mkpali ahụ nwere ike ime ka nzaghachi omume ka ukwuu mgbe ΔFosB na-emebiga ihe ókè.

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