Dopamine D1 D5 Receptors Mediate Information Saliency e Khothaletsang Hippocampal ea Nako e Telele ea Sefate sa Khale (2014)

Ke Niels Hansen 'me Denise Manahan-Vaughan

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

Eya ho:

inahaneloang

Dopamine (DA) e bapala karolo ea bohlokoa ho matlafatsong ea kelello. E eketsa mmala polokelong ea tlhahiso-leseling e itšetlehileng ka boiphihlelo, e fetisa ho se tsebe ho hopola lintho tse hlahisoang. Boemong ba synaptic, polokelo ea tlhahisoleseling e itšetlehileng ka boiphihlelo e fanoa ke polasetiki ea synaptic, mme e fuoa bohlokoa ba eona bakeng sa ho etsoa ha mohopolo, ha ho makatse hore ebe DA e na le neuromodulator ea mantlha ho matlafatso ea polasetiki ea synaptic, haholo-holo ea plastiki e phehellang nako e telele ea nako: E hopotsa mohopolo oa nako e telele. Hippocampus, eo ke sebopeho sa bohlokoa bakeng sa ts'ebetso ea synaptic ea semantic, episodic, spatial, le kumbukumbu tse nyarosang, e anngoe ka kotloloho ke DA, ka memori ea D1 / D5 e paka bohlokoa ba memori e itšetlehileng ka hippocampus. Ntle le moo, li-receptor tsa D1 / D5 li bohlokoa haholo ho fetiseng thepa ea bohloka le moputso ho tlhahisoleseling e ntseng e sebetsoa ke hippocampus. Ba boetse ba tsamaisa tlhahiso ea mefuta e phehellang ea polasetiki ea synaptic, mme ba fuoe litlaleho tsa hore bokhoni ba nako e telele le khatello ea maikutlo ea nako e telele li kenyelletsa likarolo tse fapaneng tsa boemeli ba sepakapaka, sena se fana ka maikutlo a hore li-receptors tsa D1 / D5 li ka tsamaisa mofuta le litekanyetso tsa tlhahisoleseling e bolokiloeng. ka hippocampus. Ka lebaka la lipatlisiso tsena, re etsa tlhahiso ea hore D1 / D5 receptors gate hippocampal ea nako e telele ea memori le memori e be karolo ea bohlokoa ho fetiseng thepa ea bohloka le moputso ho tlhahiso-leseling e ntseng e sebetsoa ke hippocampus.

Keywords: kelello, hippocampus, ho ithuta le ho hopola, ho hlahloba, polasetiki ea synaptic

Eya ho:

Selelekela

Dopamine (DA) ke neurotransmitter tsamaisong ea methapo e bohareng eo e leng ea li-catecholamines (Carlsson et al. Ka 1962). Li-neurons tsa DA li arotsoe ka har'a litsamaiso tsa dopaminergic ho latela libaka tsa bona tsa bolulo. Litsela tse 'ne tsa axonal dopaminergic pathways li hlalositsoe: 1) nigrostriatal, 2) mesolimbic, 3) mesocortical, le 4) tuberoinfundibular (Vallone et al. 2000). DA e tšehetsa likarolo tse ngata mesebetsing ea boko e amanang le ts'ebeliso ea kelello: E laola ho hopola, ho susumetsa, maikutlo, ts'ebetso ea makoloi le kopanyo ea neuroendocrine (Horn et al. 1979; Fluckiger et al. 1987) mme e lokolloa kamora ho noha (Ljungberg et al. 1992), sensory sensent (Ntle ho 2004)Bromberg-Martin et al. 2010), kapa sepheo sa ho matlafatsa (moputso)Schultz et al. 1993). Ka mashome a lilemo tse ngata, karolo ea eona ho mathata a ts'oaetso le lefu la boko e ithutiloe ka matla. Sena se hlahisitsoe ke maikutlo a hore mokokotlo o tlase oa DA o hlaha sebakeng sa basal ganglia sa bakuli ba nang le lefu la Parkinson (Ehringer le Hornykiewicz 1960) le hore dysfunctions tsa DA li kenya letsoho mafu a tlhalohanyo a kang schizophrenia (Goto le Mohau 2007; Lodge le Mohau 2011), bokhoba ba lithethefatsi (Robinson le Berridge 1993), tlhokomeliso khaello ea khatello ea kelello (Del Campo le al. 2011), Mme mohlomong le lefu la Alzheimer (Kumar le Patel 2007; Jürgensen et al. 2011).

Bopaki ba boithuto bo fana ka maikutlo a hore DA e sebetsa hantle haholo bakeng sa phetisetso ea polasetiki ea "haptocampus" e itšetlehileng ka "synaptic".Jay 2003; Lisman le Mohau 2005; Lisman le ba bang. 2011). Litlamorao tsena li kopantsoe ke lihlopha tse peli tse ikhethileng tsa li-receptor tsa DA: Li-receptor tsa D2 / D1 (D5-like) le li-receptors tsa D1-like (Tiberi et al. 1991; Vallone et al. 2000; Beaulieu le Gainetdinov 2011) (Feie. 1), moo, lilemong tsa morao tjena, li-receptor tsa D1 / D5 li amohetseng tlhokomelo e eketsehang. Sena ke hobane karolo ea bohlokoa eo ba e phethang ho taolo ea polasetiki e tsamaeang ka bobeli ea hippocampus-wate (mechini eo ho lumeloang hore e ithuta ka tlase) le memori e itšetlehileng ka hippocampus (Huang le Kandel 1995; Lemon le Manahan-Vaughan 2006; Bethus et al. 2010; Elena h et al. 2011; Da Silva et al. 2012). Ho khahlisang, li-receptor tsa D1 / D5 li laola mefuta ka bobeli ea pheello (> 24 h) polasetiki ea synaptic mme e bonahala e kenya letsoho ka mokhoa oa bohlokoa ho tšoaeeng tlhaiso-leseling e le buka e ncha kapa ea bohlokoa (Davis et al. 2004; Ntle ho 2004; Lemon le Manahan-Vaughan 2006, 2011), eo le eona e susumetsang ka matla khokahanyo ea memori ea hippocampus le ho e boloka (Adcock et al. 2006). Li-receptors tse kang D2, ka lehlakoreng le leng, li bonahala li sa bohlokoa bakeng sa ts'ebetso ea tlhahisoleseling e itšetlehileng ka hippocampus, ekaba maemong a polasetiki ea synaptic kapa sebopeho sa memori (Kulla le Manahan-Vaughan 2003; Xing et al. 2010). Ho kenngwa tshebetsong ha D1 / D5 receptors ho fetola thabo e matla ho hippocampus (Ito le Schumann 2007; Hamilton le ba bang. 2010) ka hona susumetsa menyako bakeng sa ho kenyelletsa polasetiki ea synaptic kapa khouto ea memori. Likarolo tse fapaneng tsa hippocampal subervation tse kang dentate gyrus (DG), cornus ammonis 1 (CA1) le subiculum tse sebelisang mesebetsi e fapaneng ts'ebetsong ea tlhahisoleseling kahare ho hippocampus le tsona li fetoloa ka ts'ebetso ea li-receptors tsa D1 / D5 (Kulla le Manahan-Vaughan 2000; Lemon le Manahan-Vaughan 2006; Othmakhova le Lisman 1996; Roggenhofer et al. 2010).

Setšoantšo sa 1.

Setšoantšo sa 1.

Li-cascade tsa Signal tsa D1 le li-D5 receptors. Pontšo ea Schematic ea litsela tse fapaneng tsa molek'hule ea D1 (mabokose a mosehla) le li-receptor tsa D5 (mabokose a maputsoa) a qetellang ts'ebetsong e tloaelehileng ea CREB (mabokose a moriri o moputsoa). Crosstalk pakeng tsa Sisteme ea D1 / D5 e bontšoa ke ...

Liphetoho tse itšetlehileng ka ts'ebetso ho matla a synaptic li kenyelletsa leseli le lecha bokong. Mefuta e 'meli e meholo e ka khetholloa: 1) tšebeliso ea nako e telele (LTP; Bliss le Lomo 1973; Bliss le Collingridge 1993) le 2) khatello ea maikutlo e telele (LTD) ea matla a synaptic (Dudek le Bear 1992; Manahan-Vaughan 1997). LTP e susumetsoang feela ke ts'usumetso ea motlakase ea motlakase (polasetiki e kentsoeng ka motlakase) e tlalehiloe ka lekhetlo la pele lilemo tse ka bang 40 tse fetileng ho DG ea mmutla kamora ho susumetsa ka matla (HFS) ea tsela e monko o monate (Bliss le Lomo 1973). Hippocampal LTD e hlalositsoe ka lekhetlo la pele ho Schaffer collateral (SC) -CA1 synapses (Dunwiddie le Lynch 1978) hape e susumetsoa ke motlakase ka ts'usumetso e tlase-hangata (LFS: 1 - H H bakeng sa metsotso e 3-5). Ka bobeli liketsahalo tsena ho lumeloa hore li ithuta le ho hopola hippocampal (Bliss le Collingridge 1993; Bear 1996; Kemp le Manahan-Vaughan 2007). Monyetla ona o tšehetsoa ke lithuto tsa morao-rao tse sebetsanang le ketsahalo e tsejoang ka hore ke polasetiki e ithutoang. Mona, tšusumetso ea motlakase e fokolang ea motlakase e tlisoang ke maemo a taolo ha e fetole phetoho ea matla a basal synaptic, kapa e phahamisa polasetiki ea nakoana, e lebisang polasetiking e phehellang haeba e kopantsoe le boiphihlelo ba ho ithuta bocha.Manahan-Vaughan le Braunewell 1999; Goh le Manahan-Vaughan 2012).

Boithuto ba polasetiki bo hlophisitsoeng bo ithutoang bo fana ka maikutlo a hore PDP le LTD li ikarabella bakeng sa ho kenyelletsa likarolo tse fapaneng tsa kemiso ea memori. Kahoo, LTP e hokahane le ho kenyelletsa sebaka sa lefats'e, phetoho ea sebaka, kapa tšabo ea maemo (Straube et al. 2003; Kemp le Manahan-Vaughan 2004; Whitlock le al. 2006), athe LTD e tsamaisana le ho kenyelletsa litaba tsa tikoloho (Manahan-Vaughan le Braunewell 1999; Etkin le al. 2006; Kemp le Manahan-Vaughan 2004, 2007, 2008a; Goh le Manahan-Vaughan 2012). Menehelo e nepahetseng ea LTP le LTD ho boemeli ba sepakapaka li hokahane ka thata le likarolo tse ikhethileng tsa hippocampal (Kemp le Manahan-Vaughan 2008a; Hagena le Manahan- Vaughan 2011). Ntho e makatsang, leha ho le joalo, ke hore li-receptors tsa D1 / D5 li laola li-EPP tse phehellang ka bobeli (Huang le Kandel 1995; Lemon le Manahan-Vaughan 2006)Lemon le Manahan-Vaughan 2006), ho fana ka maikutlo a hore li-receptors tsena li fana ka matla holim'a taolo ea tlhahisoleseling e fanoeng ke mefuta e fapaneng ea polasetiki ea synaptic ho kemiso ea memori.

LTP e arotsoe ka mekhahlelo ea nakoana e boletsoeng ho 1) bokhoni ba nako e khuts'oane boo hangata bo hlokang ho kenella ka calcium, mohlala, N-methyl-d-aspartate (NMDA) receptors, 2) pele (E) -LTP e hlokang li-receptors tsa NMDA ka bobeli le ts'ebetso ea li-receptors tsa metabotropic glutamate (mGlu) (Bashir et al. 1993) le li-protein kinases (Malenka et al. 1989), le ho isa tekanyong e nyane, phosphatases; 3) morao (L) -LTP e ipapisitseng le polelo ea liphatsa tsa pele tsa lefutso (Jones et al. 2001) e hloka phetolelo ea protheine, le (4) morao-rao (LL) -LTP e hlokang mongolo oa liprotheine (Nguyen et al. 1994; Viller et al. 2010) hape e thusa ho kopanya ho kopantsoeng ha LTP (Ryan le al. 2012). Tlhahiso e tšoanang e bonahala bakeng sa LTD: Mochini oa pele (E) -LTD o ts'ehetsang ts'ebetsong ea li-receptors tsa NMDA (bonyane tikolohong ea CA1; Dudek le Bear 1992; Manahan-Vaughan 1997), li-receptors tsa mGlu (Manahan-Vaughan 1997), le li-phosphatases tsa protheine (Mulkey le al. 1993), morao-rao LTD (L) -LTD e itšetlehileng ka polelo ea gene (Abrahama le ba bang. 1994le phetolelo ea liprotheine (Manahan-Vaughan le al. 2000; Parvez le ba bang. 2010), le morao haholo (LL) -LTD e hlokang hore ho tsamaisoe liprotheine (Kauderer le Kandel 2000). Le ha e le motlakase o kentsoeng ka motlakase le ka mokhoa o tataisang ho ithuta, o tšoana ka tsela e tšoanang mananeong a bona a tlase (Manahan-Vaughan 1997; Popkirov le Manahan-Vaughan 2011), li bonts'a thepa e ikhethang. Mohlala, ho ithutoa ntle le ho se susumetsoang ke motlakase ka motlakase o phehellang ho hloka beta-adrenoreceptors (Kemp le Manahan-Vaughan 2008b), Le Madronal et al. (2009) e bonts'itse hore ts'ehetso ea ho hula ka marang-rang e entsoe ka tsela e fapaneng ka ho fetoloa ke motlakase oa LTP kapa liphetoho tsa matla a synaptic tse hlahisoang ke boemo ba mahlo ba mahlo (ke hore, ho ithuta ho tsamaisanang le polasetiki). Leha ho le joalo ho ka etsahala hore ebe polasetiki e tataisoang ke ho ithuta e ameha haholo ho li-neuromodulation, mme e le ea mmele ho feta polasetiki e hlahisitsoeng ke ts'usumetso ea motlakase e le 'ngoe, e ka hlalosang lintlha tse boletsoeng ka holimo.

Hippocampus e kenya letsoho hore ho be le boits'oaro bo bongata bo joalo ka ho tšoenyeha (Engin le Treit 2007, boitšoaro bo lebisitsoeng ho sepheo (Pennartz et al. 2011), ts'ebetso ea tlhahisoleseling, boits'oaetso bo sebetsang, le sepheo sa ho fumana sebakaHölscher 2003). Empa ho makatsang le ho feta, ho lumeloa hore likarolo tse fapaneng tsa hippocampal li etsa likarolo tse fapaneng tsa ho theha mohopolo oa ho hopola. Le ha DG e kentsoe tšebetsong karohano ea lipaterone, moo tlhahiso-leseling e ts'oanang e nkoang e sa tšoane, setereke sa CA3 se etsa ts'ebetso ea papiso, ka moo tlhahisoleseling e kenang e lebisang ho khutlisong e felletseng ea moemeli ea bolokiloeng, haeba tlhahisoleseling eo e kentse letsoho pejana theho ea memori (Lee et al. 2004; Goodrich-Hunsaker et al. 2008). Sebaka sa CA1 ho lumeloa hore se kopanya leseli le tsoang likarolong tse ling hape le nka karolo ho bonoeng ha litšila (Lismann le Otmakhova 2001). Ka lebaka la karohano ena ea basebetsi, mohlomong ha ho makatse hore ebe li-receptors tsa D1 / D5 li fana ka tšusumetso e kholo ho polasetiki ea synaptic mehahong ena. Mona, ho tlameha ho hlakisoa hore karolo ea li-receptor tsena sebakeng sa CA3 ha e so hlahlojoe.

Eya ho:

Ho lokolloa ha DA ho Hippocampus

DA e lokollotsoe litulong tsa axon tse lulang hippocampus (Frey et al. 1990), e simolohang mehloling ea midbrain le sebaka sa ventral tegmental (VTA, sehlopha sa lisele tsa A10 ka nomenclature ea rat), e nang le mohloli o ka sehloohong. Ho lokolloa ho hlaha hippocampus metsotso e itseng ka mor'a ho pepesetsoa bocha ho hippocampus (Ihalainen et al. 1999). Sena se bolela hore DA ke karolo ea bohlokoa ho nolofatseng ts'ebetso ea tlhaiso-leseling ea rialo hippocampus. Ho li-temporoammonic (TA) li-synapses, DA e sebetsa ka makhetlo a mangata a susumetsang (5-100 Hz) e le fensetere e phahameng e ntlafatsang likarabo lipokellong tse phahameng tsa maqhubu, ha e ntse e fokotsa ts'usumetso ea likatsetso tse tlase-hangata (Ito le Schumann, 2007). Ka mokhoa o makatsang, LTP ho li-synapses tsa SC-CA1 ha e amoheloe, athe LTP ho li-synapses tsa TA e ntlafatsoa ke DA. Sena se fana ka maikutlo a hore DA e eketsa bohlokoa ba tlhaiso-leseling e fetisoang ho tsoa lethathamong le kenang kahare ho thelekiso ea TA ka kotloloho ho hippocampus, ha e bapisoa le tlhaiso-leseling e "sebetsoang kahare" ho li-synapses tsa SC-CA1, tse fetolang litaba tsa tlhahisoleseling le mofuta oa polokelo ea tlhahisoleseling ka ho susumetsa tsela ea phetoho ea boima ba methapo ea kutlo. Sena se ka boloka tumellano ea tlhahiso-leseling e ncha le tlhaiso-leseling e neng e entsoe nakong ea ha e tsoa hippocampus.

VTA ha se eona feela mohloli oa DA bakeng sa hippocampus. Ntle le VTA, hippocampus e amohela litlatsetso tse tsoang sebakeng sa retrorubral A8 le substantia nigra par compacta A9 (Ha a et et al. 1979) hape e buisana le li-nuclei tse ling tsa dopaminergic tse kang li-nucleus accumbens (NAcc; Figs 2 'me Le3) .3). Mohlala, merero ea mesocortical DA ho tloha VTA ho ea pele pele (PFC) e ka bapala karolo ea bohlokoa ho fetoleng ts'ebetso ea tlhahisoleseling ka tšebelisano-hloko ea hippocampus-PFC (Seamans et al. 1998; Goto le Mohau 2008a). Ntle le moo, le ha e sa sebetse ka kotloloho ho hippocampus, NAcc (hammoho le ventral pallidum, VP) e sebetsa joalo ka letsoho le tlase la hippocampal-VTA loop, e sebeletsa ho kopanya le lets'oao le sa tsebeng ka tlhahisoleseling le sepheo (Lisman le Mohau 2005; Likokonyana 2 'me Le3) .3). Ntle le karolo ea eona ea mantlha ea ho kenya lipakete tsa limbic le cortical, NAcc e kenya letsoho ho ntlafatseng boitsoaro bo tataisang (Gruber et al. 2009) le ho thusa ho fana ka tlhaiso-leseling e itšetlehileng ka sebaka sa hippocampal ho fumana taolo holim'a thuto e monate (Ito le Hayen 2011). Karolo ea NAcc ho ts'oereng litlatse e hlahlobiloe libakeng tse ling ka lintlha tse ngata (Mohau et al. 2007; Goto le Mohau 2008b; Yin et al. 2008).

Setšoantšo sa 2.

Setšoantšo sa 2.

Khokahano ea anatomical pakeng tsa hippocampus le dopaminergic nuclei. Lekala la VTA, retrorubral (RRF), le LC kaofela li romela likhakanyo ho hippocampus (HPC). Mesebetsi ea hippocampus ka lehlakoreng le leng, e ea ho NAcc e hokahaneng le VTA ...

Setšoantšo sa 3.

Setšoantšo sa 3.

Tsamaiso ea polasetiki ea hippocampal synaptic ke VTA le li-nuclei tse ling tsa dopaminergic. Molao oa dopaminergic oa polasetiki ea hippocampal synaptic le marang-rang a ka tlase li bontšoa mona. Metsu e putsoa e bonts'a ntho e ncha e hlahisitsoeng ea VTA-hippocampal ...

Ha re e nka hammoho, karolo e tsejoang ea "dopaminergic nuclei" e kenang hippocampus e ts'ehetsa hore DA e lokollotsoe ke boiphihlelo le boiphihlelo bo amanang le moputso le hore leseli lena le thusa hippocampus ho eketsa moelelo tlhaisong-leseling eo e e sebetsang. Ka mokhoa ona, bohloka bo hlahisoa ke tlhahisoleseling e bolokiloeng. Taolo e lekanyelitsoeng ea PDP le LTD libakeng tse fapaneng tsa hippocampal suburbs ke mokhoa o mong oo ka oona hippocampus ebe o kopanya le ho kenyeletsa tlhahisoleseling ena moemeleng oa memori kapa moemeli oa sebaka.

Eya ho:

Tšusumetso ea D1 / D5 Receptors ho LTP ho DG

DG ke "tsela" e sebetsang ho hippocampus. Liphetoho tse kopakaneng tsa PDP e kentsoeng ka motlakase li tlalehiloe ka mor'a ts'ebetso ea li-receptor tsa D1 / D5 mohahong ona (Lethathamo 1A), empa ha e le hantle, ho entsoe thibelo ea PDP kamora ho hlekefetsoa ha D1 / D5Yanagihashi le Ishikawa 1992; Kusuki et al. 1997; Swanson-Park et al. 1999). Sena se fana ka maikutlo a hore li-receptors tsena li bapala karolo ea bohlokoahali ho bona hore na PMP e etsahala ho DG ha ho tluoa menahanong e tlang. D1 / D5 receptor activation nakong ea letšoao la "moputso" kapa "ntho e ncha" e khothalelitsoe ho eketsa thabo ea DG (Hamilton le ba bang. 2010) joalo ka leseli lena le senolang maikutlo le utloisang bohloko le fetisa boitsebiso bo bulehileng le ho phunyeletsa le DG ho kenya potoloho ea sebaka sa hippocampal CA3-CA1 (Heinemann le ba bang. 1992; Hamilton le ba bang. 2010). Sena le sona se ka amana le ts'ebetso ea DG ha ho phetheloa mohlala.Kesner le ba bang. 2000).

Lethathamo 1

Tafole 1

D1 / D5 li-receptors le polasetiki ea hippocampal synaptic

Tlhahisoleseling e matlafatsang ka kutloisiso ea lefatše lohle e boetse e tšehetsoa ke DA. Mofuta ona oa ho ruruha o ka lumella ts'ebetso ea marangrang a oscillatory pakeng tsa libaka tse fapaneng tsa boko tse kenyelletsoang ho ithuteng (Buzsaki le Draguhn 2004). D1 / D5 ts'ebetso ea "receptor" e ka etsa hore mohlala o fokotsehe oa ho phatloha hoa leqhubu la "methapo" ea methapo ea methapo ea methapo e kenang hippocampus (Fitch le ba bang. 2006). Ntle le moo, DA e hatella li-oscillations tsa cholinergic sebakeng sa CA3 ka ts'ebetso ea D1 receptor (Weiss et al. 2003). Ho khothalelitsoe hore DA ka ho khetheha e fetola mokhoa oa ho thunya khafetsa oa li-neurons (li-voltays tsa theta le tsa gamma; Ito le Schumann 2007) tse hlokometsoeng ho enthorinal cortex nakong ea boits'oaro bo bobe ba litoeba (Chrobak et al. 2000) ka hona ho fetola litaba tsa tlhahisoleseling.

Eya ho:

Tšusumetso ea li-Receptors tsa D1 / D5 ho LTP Setereke sa CA1

Ho fapana le DG, moo ho amehang L-LTP feela, liphuputso tsa li-vitro tsa li-synapses tsa SC-CA1 li bonts'itse hore bobeli ba E-LTP (Otmakhova le Lisman 1996) le L-LTP (Frey et al. 1991; Huang le Kandel 1995) li thibetsoe kapa li fokotsehile (Swanson-Park et al. 1999) ke mohanyetsi oa D1 / D5, athe agonists ea D1 / D5 receptors e lebisa ho E-LTP e ntlafalitsoeng (Otmakhova le Lisman 1996). Boholo ba bobeli ba E- le L-LTP le bona bo fokotsehile haholo metsong ea hippocampal ho tloha D1 receptor - / - litoeba ha li bapisoa le litoeba tsa mofuta oa hlaha (Granado et al. 2008). Tumellanong le liphumano tsena, liphuputsong tsa vivo li bonts'itse hore HFS-e kenyellelitsoeng ea HPS ho li-synapses tsa SC1 CA1 e nolofalitsoe ke ts'ebetso ea D5 / DXNUMX receptor ho etsa ka mokhoa oa mahala likhoto (Lemon le Manahan-Vaughan 2006; Tafole 1A). Leha ho le joalo, antagonism ea D1 / D5 e thibela feela L-LTP ho li-synapses tsa SC1 / DXNUMX (Lemon le Manahan-Vaughan 2006). Phapang lipakeng tsa li-in vitro le lithuto tsa vivo li kanna tsa amana le mefuta e fapaneng ea protocol ea ts'usumetso e neng e sebelisoa ho eletsa LTP ea robustness le durations tse fapaneng.

Eya ho:

Kameho ea ketsahalo ea D1 / D5 Receptor mabapi le Phokotso ea LTP

Leha e se mokhoa o phehellang oa polasetiki ea synaptic, depotentiation e na le ho buoa maemong a D1 / D5 regulation of hippocampal synaptic plasticity (Lethathamo 1C). Depotentiation ke ntho e khahlisang e etsahalang ha LFS e kenngoa ka fensetere ea nako e khuts'oane haholo (metsotso e 30 e phahameng ea ho hohela LTP (Staubli le Lynch 1990; Kulla et al. 1999) 'me ho bile le tlhahiso ea hore e kenyelletse mokhoa o sebetsang oa ho lebala o sebetsang kapa mohlomong oa ho sitisa ho ithuta. Mofuta ona oa synaptic plasticity o ikhethile ho LTD, kaha e sa kopanye phapang e le 'ngoe ea phosphorylation / dephosphorylation ea α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor receptor (Lee et al. 1998) hape e na le maikutlo a fapaneng ho etsa mohlala, mGlu receptor ligands (Manahan-Vaughan 1997; Fitzjohn et al 1998; Kulla et al. 1999; Kulla le Manahan-Vaughan 2008). Karolo e ngoe ea depotentiation ke taolo e kopanyang ea ketsahalo ena, joalo ka mohlala oa phuputso e entsoeng ka vitro ho likhoto tse bonts'ang hore motsoako oa liprotheine tse amanang le polasetiki (PRPs) ke L-LTP kenyelletsong e le 'ngoe e nolofalitse E- ho L-LTD kenyelletsong e ngoe. Ka hona, polasetiki ea nako e telele ho kenyelletso e le 'ngoe ea "synaptic" e susumetsoa ka mokhoa o kopanetsoeng ke li-PRPs tsa karohanyo e ngoe ea synaptic, ts'ebetsong e bitsoang "tagging"Sajikumar le Frey 2004). Ho kopanya polasetiki nako e telele le ho kopanya li-synaptic le tsona ho bonahala li its'etleha ho ts'ebetsong ea D1 / D5 receptor (Sajikumar le Frey 2004).

Ho khahlisang, ho qhekella ha D1 / D5 receptor ho ama deposentiation ea LFS e khothalletsoang ke LPP ka bobeli ka vitro le vivo (Otmakhova le Lisman 1998; Kulla le Manahan-Vaughan 2000). D1 / D5 li-receptor agonists li fokotsa ho fokotsoa ha PMP ke LFS ho CA1 le DG, athe bahanyetsi ba D1 / D5 receptor ba sitoa ho etsa sena (Kulla le Manahan-Vaughan 2000) mohlomong ka cyclic 3'5 ′ adenosine monophosphate (cAMP) - mochini o itšetlehileng ka oonaOtmakhova le Lisman 1998).

Haeba depotentiation e akaretsa ho lebala, ho fana ka maikutlo a hore ts'ebetso ea D1 / D5 receptor e ka sitisa ts'ebetso ena. Joalo ka ha depotentiation ea LTP e le ts'ebetso e latelang-pele ho qaptjoa 'me ka mor'a moo e thehiloe, ho bolela hore ts'ebetso ea D1 / D5 receptor e ka hlahisa "qeto" ea ho lebala tlhahisoleseling e neng e reretsoe ho bolokoa nako e telele. Hape, monyetla ona o sebetsa hantle bakeng sa li-receptors tsena ho tsamaisanang le boits'oaro ba tsebo.

Eya ho:

Matla a mosebetsi oa D1 / D5 Receptor ho Hippocampal LTD

LTD ho isa bohōleng bo itseng ke setšoantšo sa seipone sa LTP, se kenyelletsang ho fokotseha hoa matla a synaptic e etsahalang kamora tšusumetso e amanang le hippocampus. Lilemong tsa morao tjena, ho ile ha totobala hore ketsahalo ena ke mochine oa polokelo ea tlhahiso-leseling o ka bang oa sebelisana le LTP ho hlahisa tlhahiso ea maqhubu le / kapa memori (Kemp le Manahan-Vaughan 2007). Bakeng sa ketsahalo ena, joaloka PDP, li-receptors tsa D1 / D5 le tsona li bonahala li bapala karolo ea bohlokoa. Ho fapana le LTP, moo sebaka sa CA1 le DG li ithutoang ka matla, ho fihlela joale, tlhaiso-leseling e teng feela mabapi le litlamorao tsa D1 / D5 ho LTD sebakeng sa CA1 (Letlapa 1B).

E-LTD, e hlohlellelitsoeng ke LFS ea CA1 synapses, e tsamaisoa ke D1 / D5 receptor agonism ho vitro (Chen et al. 1995; Liu et al. 2009). Ka lehlakoreng le leng, E-LTD e koetsoe ke mohanyetsi oa D1 / D5 receptor ho CA1 synapses in vitro (Chen et al. 1995). Ntle le moo, liphuputso tsa in vitro li bonts'itse hore li-E-le L-LTD ka har'a maqhubu a CA1 li its'etleha ho ts'ebetsong ea D1 / D5 receptor (Mockett et al. 2007; Liu et al. 2009). Boitsebiso ba vivo bo lumellana le liphetho tsena, kaha D1 / D5 receptor agonism e thusa LFS-induction E-LTD le L-LTD, athe D1 / D5 receptor antagonism e thibela LFS-e susumetse E-LTD le L-LTD (Lemon le Manahan-Vaughan 2006). Leha ho le joalo, phuputsong e le 'ngoe ea vitro, Don / D1 receptor agonism e khutlisitse karolo e itseng ea LFS-induction LTD (Mockett et al. 2007). Litlamorao tsena tse fapaneng tsa vitro li ka bakoa ke ts'ebeliso ea protocol e fapaneng ea LFS [1200 × 3 Hz (Mockett et al. 2007khahlanong le 450 × 1 Hz (Chen et al. 1995)] e hlahisang LTD ea boholo bo fapaneng le nako. Ho vivo, 1-Hz LFS e sebelisang <600 pulses e hlahisa khatello ea maikutlo ea nakoana (STD) ho li-synapses tsa CA1 (Popkirov le Manahan-Vaughan 2011), athe 3-Hz e tsosa litlamorao ho feta (Manahan-Vaughan 2000). Phapang taolong ea D1 / D5 li-receptor agonists tsa khatello ea maikutlo ea synaptic ea matla a fapaneng le durations li ka sebetsa ka mokhoa o lumellanang le bohlokoa ba mefuta ena ea polasetiki bakeng sa ts'ebetso ea tlhahisoleseling: Likarabo tse fokolang li ka matlafatsoa mme likarabo tse matla li ka fokola ka mokhoa o ka nahano, e le hore ts'ebetso ea tlhahisoleseling e ntlafalitsoe.

Eya ho:

D1 / D5 li-Receptors le Plato e Ithutoang

Boithuto ba vivo bo bonts'itse hore ho ithuta ho nolofalletsa E-LTP le L-LTP ho ithuta ka sebaka se senotsoeng ho ka thibeloa ke ho hanyetsa D1 / D5 receptor antagonism ho li-synapses tsa CA1 (Li et al. 2003; Lemon le Manahan-Vaughan 2006). Ntle le moo, ts'ebetso ea pharmacological ea li-receptors tsa D1 / D5 e etsisa boits'oaro bo potlakileng ba moea ba ts'usumetso ea PDP (Li et al. 2003). D1 / D5 receptor agonism e nolofalletsa STD ho LTD ho CA1 synapses ho vivo (Lemon le Manahan-Vaughan 2006). Sena se ts'ehetsa monyetla oa hore ts'ebetso ea li-receptor tsa D1 / D5 e theole monyako oa CA1 LTD. Ntle le moo, ho tlalehiloe karolo e sebelisoang bakeng sa li-receptor tsa D1 / D5 ho tse ithutileng ho ithuta tsa LTD. Mona, L-LTD e neng e hlophisitsoe ke lipatlisiso tsa nalane ea maqhubu e ne e thibetsoe ke bohloeki ba D1 / D5 receptor antagonism (Lemon le Manahan-Vaughan 2006). Patlisiso ea nalane ea sebaka sa nalano e kopane le ts'usumetso e kopanetsoeng e kopantsoeng le ts'ebetso ea D1 / D5 receptor e boetse e nolofalletsa khatello ea maikutlo butle-butle ho li-synapses tsa CA1, ka hona e ts'ehetsa hore ts'ebetso ea D1 / D5 receptor e ka theola monyako oa polokelo ea tlhahisoleseling ke LTD ho li-hippocampal synapses (Lemon le Manahan-Vaughan 2011; Tafole 1B). Ka hona, li-E- le L-LTP tse ithutoang ka ho ithuta li ka fetoloa ka ho kenya li-receptor tsa D1 / D5 (Lethala 1A). Hape, ho fumana hona ho hokahanya li-receptor tsa D1 / D5 ka matla le boiphihlelo ba maikemisetso mme e fana ka maikutlo a hore li-receptors tsena e ka ba e 'ngoe ea lintlha tse fanang ka leseli le bohlokoa ba tlhahisoleseling e kenang ea maikutlo e fihlang hippocampus.

Eya ho:

Ke eng e etsang hore ho be le phapang ho D1 / D5 Regulation of Hippocampal Synaptic Plasticity?

Ho nkuoa hammoho, lithuto tsena li tšehetsa hore li-receptor tsa D1 / D5 ha li na phello e ts'oanang ho PDP sebakeng sa CA1 le DG. Sebaka sa CA1 se shebahala se tebile haholoanyane, ka bobeli E-LTP le L-LTP li laoloa ke li-receptors tsa D1 / D5. Ho DG, ka lehlakoreng le leng, ke L-LTP feela e amehang. Ho kenyelletsa khokahanong ena e sebetsang ke molawana oa li-receptor tsa D1 / D5 tsa LTD, depotentiation le polasetiki e nolofalitsoeng ea ho ithuta. Taolo ena e lebisitsoeng ke li-receptor tsa D1 / D5 tse nang le likarolo tse ngata tse fapaneng tsa polasetiki ea synaptic li ka amana le polelo e amanang le li-receptor tsa D1 / D5 hippocampus, le kopanyo e haufi ea li-receptor tsena ho saena li-cascade. Li-receptor tsa D1 le D5 ka bobeli li hlahelletse ka har'a lisele tsa pyramidal tsa hippocampus ho litšoene (Bergson et al. 1995) le li-neuron tsa pyramidal ho CA1-3, ho kenyelletsa lisele tse methapo ea methapo le li-radiatum li hlahisa li-D1 / D5 receptors ka likhoto (Fremeau et al. 1991). D1 / D5 receptor mRNA e boetse e kenngoa ka seleng liseleng tsa granule tsa DG le ka ntle ho methapo e mengata ea methapo ea kutlo ea subiculum (Fremeau et al. 1991). Ntle le moo, li-receptor tsa D5 li hlahisoa liseleng tsa hilus le granule tsa DG, ka liseleng tsa "pyicidal" tsa subiculum, le tikolohong ea CA1-CA3 ea litoeba, batho le litšoene (Ciliax et al. 2000; Shah et al. 2000). Kahoo, ho ajoa ha li-receptor tsa D1 / D5 ho batla ho hlaha hippocampus. Leha ho le joalo, liphapang tse ling tsa ho kenella ha neuronal tsa D1 le D5 receptors li bonahala li le teng: li-receptor tsa D1 ka har'a cortex ea "cerebral cortex" li fumaneha haholo mefuteng ea dendritic, athe li-receptor tsa D5 li etsahala hangata litsong tsa dendritic ho PFC (Bergson et al. 1995). Liphapang tsena tse sa reng letho tse mabapi le ho ntlafatsoa ha li-receptor tsa D1 / D5 li ka ba le litlamorao tse sebetsang (Bergson et al. 1995). Ha lits'oants'o tsa "pyendidal dendritic" li amohela glutamatergic (Harris le Kater 1994) le dendritic shafts inhibitory gamma-aminobutyric acid (GABA) ho kenella hampe (Jones xnumx), ho ka etsahala hore li-receptor tsa D1 li kenelletse haholo ho thabo, le li-receptor tsa D5 inhibitory, neuromodulation (Bergson et al. 1995).

Patlisiso ea Immunohistochemical e ile ea hlakisa li-receptor tsa D1 ho glutamatergic thabo e nyarosang ea li-neurons tsa "granule cell" ea DG le mefuta e mengata ea likarolo tsa inhibitory GABAergic tse mahareng tsa hilus le CA3 / CA1 ka hippocampus ea "mouse"Gangarossa et al. 2012). Li-interneuron tsena tsa GABAergic li ka laola tlhahiso e kopantsoeng ea lisele tsa granule (Miles et al. 1996), e bonts'a hore DA e sebetsang ka li-interneurons tsena e ka susumetsa ts'ebetso ea tlhahisoleseling ho potoloho ea hippocampal. Sebakeng sa CA1 sa hippocampus le PFC monkey, li-receptor tsa D1 / D5 li etelletsoe pele le tsa postynaptically localized (Bergson et al. 1995), e bonts'a mekhoa e ikhethileng ea pre-and postsynaptic ea DA e kopanyang phetisetso ea matla a synaptic. Taolo e thata ea thabo bakeng sa Sistimi ea GABAergic ke taba ea bohlokoa eseng feela ho thibela liketsahalo tsa LTP hore li se ke tsa nyoloha ho fihlela liketsahalo tsa epileptiform, empa hape le bakeng sa LTD le tlhokomeliso ea thabo ea synaptic ka har'a mofuta oa tšebetso (Baudry 1986; Wagner le Alger 1995; Kullmann le al. 2000).

Ka mokhoa o makatsang, Gangarossa et al. (2012) e bontšitse hore ha ho na li-receptor tsa D1 ho CA1 stratum radiatum ea mouse, leha ts'ebetsong ena ea subregion D1 / D5 e hlokahala bakeng sa ho ithuta ho itšetlehileng ka hippocampal, memori (O'Carroll le al. 2006; Bethus et al. 2010), le polasetiki e phehellang ho li-synapses tsa SC-CA1 (Lemon le Manahan-Vaughan 2006). Sena se fana ka maikutlo a hore li-receptor tsa D5 e kanna ea ba babuelli ba pele ba litlamorao ho polasetiki ho li-synapses tsa SC-CA1. Li-receptors tsa D1 li fumanoe ho li-synapses tsa TA-CA1, leha ho le joalo (Gangarossa et al. 2012), ho fana ka maikutlo a hore ho fapana le li-synapses tsa SC-CA1, polasetiki ho li-synapses tsa TA-CA1 li ka laoloa ke li-receptors tsa D1.

Ho bohlokoa hape ho supa hore mismatch pakeng tsa dopaminergic D1 / D5 receptor phepelo le dopaminergic fiber innervations ea hippocampus e teng. Boithuto ho likhoto li bonts'itse hore dorsal hippocampus e fumana lits'oants'o tse matla tsa moferefere, empa e ne e le ka seoelo dopaminergic ho tsoa VTA (Swanson le Hartman 1975; Scatton le al. 1980). Ntle le moo, ho ile ha bonoa phapang pakeng tsa moetlo o matla oa li-receptor tsa D1 / D5 hippocampus le hoo e batlang e le sieo tsa dopaminergic fibers (Smith le Greene 2012). dopaminergic fibers projeke ho tloha VTA ho hippocampus (Scatton le al. 1980; Gasbarri le al. 1994, 1997), empa tlhahiso ena ea dopaminergic e tsoang ho VTA e shebile haholo hippocampus ea ventral, 'me ha e rale mehaho e kang stratum radiatum ea dorsal hippocampus (Swanson 1982; Gasbarri le al. 1994, 1997). Sena se tiisa potso ea hore na DA e ka susumetsa ts'ebetso ea dorsal hippocampal joang ho hang. Leha ho le joalo, maemo a DA ho hippocampus ha a itšetlehe feela ka dopaminergic innervations, joalo ka ha lesapo ho, ka mohlala, li-neurons tsa hippocampal noradrenergic li fokotsa haholo maemo a DA (Bischoff et al. 1979). Ho feta moo, likhoele tsa locus coeruleus (LC) li hlasela ka matla sebopeho sa hippocampal ho kenyelletsa le stratum radiatum (Moudy le ba bang. 1993) le ho etsa tumello ea ho lokolloa ka kotloloho ho DA ho li-fiber tsa LC tsa Noradrenergic sebakeng sa CA1 (Smith le Greene 2012). Kahoo ho ka etsahala hore DA e lokolloe litsing tsa "fiber" tsa "Noradrenergic" ho "buseletsa" maemo a fokolang a tlisoang ke VTA e kopantsoeng le DA ho ea stratum radiatum le lits'ebetso tse ling tsa dorsal hippocampal. tse arolelanoang ke likarolo tsa dorsal hippocampal.

Li-receptor tsa D1 / D5 li laola ka mokhoa o fapaneng E-LTP le -LTP ho latela maemo a hippocampal a amehang (Huang le Kandel 1995; Otmakhova le Lisman 1996; Kulla le Manahan-Vaughan 2000; Lemon le Manahan-Vaughan 2006; Granado et al. 2008). Polelo e fapaneng haholo ea li-receptor tsa D1 le D5 li ka kenella ts'ebetsong ena, ka karolo e 'ngoe, ka ho susumetsa mekhahlelo e fapaneng ea LTP, ka lebaka la hore li-receptors li kentse li-cascades tse fapaneng tsa matšoao. Ho etsa lipontšo tsa D1 receptor ho nolofalletsoa ka ho kopanya ka mokhoa o nepahetseng ho adenyl cyclase (AC), athe likarabo tsa D5 receptor li hokahanngoa haholo ka ho kopanya ho kopanya phosphoinositide (Khotso 2010; Feie. 1). Kahoo, ts'ebetso ea "receptor" efe kapa efe e tla lebisa ts'ebetsong ea phosphorylation, leha e le liprotheine tse fapaneng. Ka bobeli li-cascades (D1 le D5 receptors) li kopana ka tsela e tloaelehileng e fetohelang protheine e tsamaisang karabelo ea CAMP (CREB) e tšehetsang polasetiki ea nako e telele ea synaptic ho hippocampus (Barco le al. 2002).

Ho kenngwa tshebetsong ha AC ka li-receptors tsa D1 ho tiisa ho fetoloa ha adenosine triphosphate ho cramP ea bobeli ea intracellular messenger. Ka lebaka leo, ts'ebetso ea protheine kinase A (PKA), sepheo sa cAMP, ea eketseha (Vallone et al. 2000; Khotso 2010). Sepheo sa phosphorylation ea PKA ke DA le phofo e laoloang ka 32-kDa phosphoprotein (DARPP-32) e hlahisitsoeng ho DG ea hippocampus (DARPP-32; Khotso 2010), ts'ebetso ea eona e lebisang phihlelong ea mosebetsi oa li-receptor tsa NMDA (Cepeda le Levine 2006). Ts'ebetso ea PKA e hlokahallang DA e boetse e laola mofuta oa T-mofuta oa Ca2+ maqhubu (Drolet et al. 1997) le ts'ebetso ea "transaction factor" ea protein-calcium e tlamang likarolo le liprotheine tsa CREB tse lebisang polelo ea protheine ea CREB (Khotso 2010; Feie. 1).

Ho fapana le li-receptor tsa D1, ho supa ka tsela ea phosphoinositide ea D5 receptors e kenya phospholipase C (PLC), e kenyang hydrolysis ea phosphotidylinositol-4,5-biphosphonate ho hlahisa man messengersosa a bobeli a diacylglycerol le inositol-1,4,5-trisphosphate (Berridge le Irvine 1984). Leha ho le joalo, ts'ebetso ea li-receptor tsa D5 e ka boela ea tsosa cAMP le tsela ea PKA (Beaulieu le Gainetdinov 2011; Feie. 1). Ho boptjoa ha inositol phosphates ho baka ho ts'oaroa ha mabenkele a "calcium" a kenang kahareKhotso 2010), ka lehlakoreng le leng, ke mohato oa bohlokoa ho thuseng ha polokeho ea synaptic. Keketseho e eketsehileng ea "calcium" e kenelletsang mofuteng oa calcium oa "protein" e itšetlehileng ka protheine ea protein e tsoaloang ke calcium. 1). Kahoo, ts'ebetso ea li-receptor tsa D1 le D5 e ka lebisa ts'ebetsong ea CREB ka litsela tse peli tse ikhethileng tsa saena (Khotso 2010). Ho na le mekhoa e mengata pakeng tsa lits'ebetso tsa AC le PLC (Khotso 2010, Feie. 1). Ho kopanngoa ha li-cascade tse fapaneng tsa lets'oa la D1 / D5 receptor activation ka hona ho ke ke ha ts'ehetsa mesebetsi e fapaneng feela mabapi le taolo ea mekhahlelo ea LTP, empa hape le ea LTD (Centonze et al. 2003) hammoho le ho sebelisana le li-receptor tse ling kapa li-neuromodulators (Liu et al. 2000) hore le eona e ka susumetsa nako e telele ea li-plastiki tsa liketsahalo.

Joalokaha D1 / D5 Receptors e Matlafatsa Protein ea Lehae ho Dendrites ea Hippocampal Neurons (Smith et al. 2005), ho ka etsahala hore li-receptors tsa D1 / D5 li kenye letsoho phetolelong ea protheine e hlokahalang bakeng sa L-LTP. Tumellanong le sena, blockade ea hippocampal D1 / D5 receptors (kahare ho metsotso e 15 ea tlhahlobo e ncha) e thibela L-LTP mme e thibela mohopolo oa sebaka (Wang et al. 2010). Patlo ea nalane e etsa hore DA e lokolloe, e leng se bakang tokiso ea mofuta oa pele oa mofuta oa Arc setereke sa CA1 (Guzowski et al. 1999). Ts'ebetso ea li-receptor ea D1 le eona e ka baka keketseho ho polelo ea Zif268 le Arc / Arg3.1 ho DG mme mefuta ka bobeli e kenella ho transcriptal regulational le ho latellana ha polasetiki (Gangarossa et al. 2011). Sena se fana ka maikutlo a hore DA, ka li-receptor tsa D1 / D5, e hlohlelletsa mekhoa ea ho ngola e lebisang ho polasetiki ea nako e telele. Li-receptor tsa Hippocampal D1 / D5 li hlokoa ka ho khetheha ho susumetsa motsoako oa liprotheine tse amanang le polasetiki tse hlokahalang ho kopanya polasetiki ea nako e telele le mohopolo (Moncada et al. 2011). Seteishene sa "tagaptic" lenaneng ka mokhoa o itseng bakeng sa li-PRP tse latelang tse kang protheine kinase M zeta (Navakkode et al. 2010) e bohlokoa bakeng sa LTP e tsitsitseng (Frey le Morris 1997). Liteko tsa inro ea vitro li bontša hore ts'ebetso ea li-receptor ea D1 / D5 e ka ameha ts'ebetsong ena (Sajikumar le Frey 2004; sheba Lethathamo 1). Lithibelo tsa L-LTP tse entsoeng ke D1 / D5 receptor antagonism li ka hlalosoa ka tekanyo ea limolek'hule ka motsoako o thibelitsoeng oa protheine o susumetsoang ke khang ea li-receptor tsena.

Ketso e kopanetsoeng ea DA ea ho hohela LTD kapa LTP e kanna ea bakoa ke ts'usumetso e tlisoang ke lits'ebetso tse fapaneng tsa phosphorylation tse lebisang ho LTD kapa ho LTP (Saijkumar le Frey 2004). Ho feto-fetoha ha sebopeho se itšetlehileng sa NMDA receptor ka bobeli ba E-LTP le E-LTD ka ts'ebetso ea li-receptor tsa D1 / D5 sebakeng sa CA1 e kanna ea e-ba teng hobane lets'oao la DA le fetohela ho receptor ea NMDA ho kenya ts'ebetso ea ERK2 ts'ebetsong ena e hippocampal (Kaphzan et al. 2006). Li-receptor tsa D1 / D5 le tsona li laola receptor ea NMDA ka kotloloho (Cepeda et al. 1998; Stramiello le Wagner 2008; Varela et al. 2009) hape e ka ama mekhoa e meng e kenang ea PDP le LTD (Cummings le al. 1996), le ho supa li-cascades tse qaliloeng ke li-receptor tsa D1 / D5 tse lebisang ts'ebetsong ea CREB le synthesis ea protheine (Smith et al. 2005; Moncada et al. 2011; Sarantis et al. 2012). LTD e sebetsa liprotheine (Manahan-Vaughan le al. 2000). Ka lebaka la hore bohanyetsi ba li-receptor tsa D1 / D5 li thibela tlhokomelo ea LTD (Sajikumar le Frey 2004) ka tsela e ts'oanang le protheine synthet inhibitors (Sajikumar le Frey 2003), e ho leka ho tiisa hore DA e kanna ea ameha ka kotloloho lits'ebetsong tse hlokahalang bakeng sa tlhahiso ea liprotheine tse amanang le polasetiki tse sa amaneng le PDP feela, empa hape le LTD (Sajikumar le Frey 2004).

Eya ho:

Matla a mosebetsi oa D1 / D5 Receptor ho Ithuta ka Hippocampus-Dependent

Liphumano tse boletsoeng ka holimo li fana ka maikutlo a hore khokahano e thata haholo pakeng tsa molao oa polasetiki ea synaptic ke li-receptors tsa D1 / D5 le karolo ea tsona thutong e itšetlehileng ka hippocampus. Hippocampus e bapala karolo ea bohlokoa ho ithuteng le ho hopoleng (Eichenbaum et al. 1990; Mishkin le al. 1998) hape e kenella mohopolong oa sebaka le episodic (Burgess le al. 2002). Dopaminergic midbrain e nka karolo sebopeho sa memori ea episodic ea motho (Schott le al. 2006). Ntle le moo, ka litoeba, mohopolo oa nako e telele oa ho fumana hippocampus-mediated kutora tsa balekane ba bacha ba paired (mosebetsi oa memori-episodic-like) o hloka ts'ebetso ea li-receptors tsa D1 / D5. Ho fapana le hoo, mohopolo oa pele ha o qojoe ke antela ea D1 / D5 receptor antagonism (Bethus et al. 2010), mme DA ha e na phello mohopolong o seng o thehiloe kapa ho khutla (O'Caroll et al. 2006; Tafole 2).

Lethathamo 2

Tafole 2

Li-receptors tsa D1 / D5 le thuto e itšetlehileng ka hippocampus

Phekolo ea agonist ea D1 ho likhoto e ntlafatsa mohopolo oa moea o amanang le sebaka sa hippocampus (Bach et al. 1999; da Silva et al. 2012) ntle le ho ama mohopolo o sa tsotelleng (da Silva et al. 2012). Ka lehlakoreng le leng, bahanyetsi ba D1 / D5 receptor ba senya nako e telele ea nako le ea nako e telele (Elena h et al. 2011; da Silva et al. 2012). Boithuto ho litoeba tsa transgenic li bontša hore D1 receptor (El-Gundi et al. 1999) mme eseng D3 kapa li-receptor tsa D5 li bohlokoa bakeng sa thuto ea sebaka (Granado et al. 2008; Xing et al. 2010). Receptor ea D1 e bohlokoa hape bakeng sa ho kenyelletsa tikoloho ea lipalesa le boemeli ba hippocampal ba polasetiki (Tran le al. 2008). Receptor ea D1 e bohlokoa molemong oa ho kenya Zif268 le arc, liprotheine tse hlokahalang bakeng sa phetoho ea E-LTP ho L-LTP le ho kopanngoa hoa memori ho liphoofolo tse anyesang (Granado et al. 2008), le ts'ebetso ea li-receptor tsa D1 / D5 lia hlokahala nakong ea kh'outu ea memori ho hlahisa lethathamo la memori le phehellang hippocampus (O'Carroll le al. 2006). Liphetoho tse itšetlehileng ka ho ithuta ho matla a synaptic a mefuta e meng ea thuto e itšetlehileng ka hippocampal, joalo ka boemo ba mahlo ba mahlo (Kuo et al. 2006, Suzuki 2007; Madronal et al. 2009), hape e fetotsoe ke ts'ebetso ea D1 receptor (Ortiz le al. 2010). Liphumano tsena li fana ka maikutlo a hore ts'ebetso ea li-receptor tsa D1 / D5 ke karolo ea bohlokoa ho thehoeng ha mohopolo oa nako e telele bokong ba mammary.

Eya ho:

Karolo ea Signal Novelty

Maikutlo ana a phahamisa potso ea hore na ke eng e fetolang liphetoho maemong a DA hippocampus le monehelo o amanang le D1 / D5 receptors ho polasetiki ea synaptic le sebopeho sa memori. Ntho e ka sehloohong ke karabelo ea bocha. Mohloli oa bohlokoahali oa ho lokolloa ha DA ho hippocampus o tsoa ho VTA, li-neuron tsa dopaminergic tseo e tsoa ho tsona ka lebaka la ts'usumetso ea pale e ncha (Ljunberg et al. 1992; Grenhoff et al. 1993) le semelo sa ho phatloha ho phasic (Ljunberg et al. 1992). Ha maqhubu a karabelo ea ts'usumetso ea buka e ncha a tšoana hantle pakeng tsa VTA le hippocampus (50-200 ms), Lisman le Grace ba hlahisitse mohlala oa monahano o bonts'ang tlhaiso-leseling ea pale e qalisoang pele ke hippocampus 'me ea bobeli, e lebisang ts'ebetsong e sa tobang ea VTA ka NAcc le VP. Ts'ebetso e sa tsejoeng ea VTA e etsahala ka boiketsetso bo thabisang ba glutamatergic ho tloha subiculum ho NAcc, probello ea Gabaergic ea inhibitory ea NAcc ho VP, qetellong, ke inhibitory GABAergic projeke ea VP ho VTA (Legault et al. 2000; Floresco et al. 2001, Legault le Bohlale 2001; Likokonyana 2 'me Le33).

Ho 'nile ha fanoa ka tlhahisoleseling e bolokiloeng leseli la sensory tsamaisong ea DG-CA3 e romella leseli la "ho nahana esale pele" ho CA1 ka SC e "bapisang" tlhaiso-leseling ea senoloa sa nalane e tsoang tseleng e monate. Letshwao lena la "mismatch" le hlahisang VTA ka tsela e sa tobang (NAcc le VP) ea hippocampal-VTA loop (Lisman le Mohau 2005). Lithuto tse nang le phetoho e matla ho batho li ts'ehetsa ho kenya ts'ebetso ea maikutlo a hippocampal-VTA e itšetlehileng ka eona.Wittmann le al. 2005; Adcock et al. 2006). Lintlha tse ling hape tse amanang le batho ka nepo li totobisitse ho kopanngoa ha VTA, hippocampus, le VP ka ts'usumetso e ncha e ncha (Bunzeck le Düzel 2006), 'me tlhahlobo ea vivo ho likhoto e bonts'itse hore tlhahiso ea lipale e ile ea hlohlelletsa ho phahama ha DA ho NAc ho its'etleha ts'ebetsong ea tlhahisoleseling e tsoang ho "subral" subralulum ea hippocampus (Legault le Bohlale 2001).

Ha li kopantsoe, liphumano tsena li ts'ehetsa hore tlhaiso-leseling e ncha e ka qala ho ngolisoa ke hippocampus, ka mor'a moo, e etsa hore VTA e hlahise ponts'o e sa tloaelehang eo ka mora moo e nang le tšusumetso ea tlhahisoleseling ea hippocampal. Tumellanong le sena, ntlafatso ea polasetiki ea nako e telele ho DG e hlohlellelitsoeng ke HFS e bonoa ha rat e beoa tikolohong ea nova (Davis et al. 2004), ho fana ka maikutlo a hore bocha bo na le tšusumetso e bonts'ang thabo ea hippocampal. Ka hona, bonyatsi bo etsa hore mesebetsi ea hippocampal e tsoele pele.Vinogradova 2001), likhoto (Jenkins et al. 2004), le batho (Tulving et al. 1996; Strange le Dolan 2001). Ntle le moo, ke hippocampus eseng VTA e hlahang e qala karabo e ncha: Mekhoa e amanang le ketsahalo e amanang le liketsahalo tsa hippocampus ea katse (Ruusurvita et al. 1995) le Rat (Brankack le al. 1996) bonts'a hore hippocampus e baka ho thunya ho amanang le bohlanya ha VTA. Ka mokhoa o ts'oanang, tokollo ea DA e etsahala kamora ho susumetsa maikutlo ho noha ka hippocampus ea mouse (Ihalainen et al. 1999) le matšoao a bonoa a hippocampal a makatsang a eketsang palo ea li-neurons tsa DA VTA tse entsoeng ka matlaFloresco et al. 2003; Likokonyana 2 'me Le3) .3). Puisano pakeng tsa hippocampus le VTA e bonahala e hlokahala bakeng sa polokelo ea nako e telele ea tlhaiso-leseling. Ka hona, ho ikopanya ho kopaneng hoa potoloho ea VTA / hippocampus ho thusa ho kenyeletsa tlhahisoleseling ea pale ea memori ea nako e telele ka tokollo ea VTA DA (Mizumori et al. 2004; Lisman le Mohau 2005; Wittmann le al. 2005; Adcock et al. 2006).

Ho hlophisoa ha bocha ke hippocampus, leha ho le joalo, e kanna ea tšehetsoa ke likarolo tse ling ntle le VTA. Mohlala, "Noradrenergic LC e chesa ka mokhoa o phahameng" ho arabela phihlelong ea lipale tse ncha (Sara le al. 1994). Ts'ebetso ea sebopeho sena e fetola thabo ea hippocampal (Kitchigina et al. 1997) mme e tsamaisa polasetiki ea synaptic (Lemon et al. 2009). Empa LC le VTA li hokahane maemong ohle a sebetsang le a anatomical. Phuputso e sebelisitsoeng ka mekhoa ea ho latellana ea morao-rao le ea ho hula morao e bontšitse hore LC le VTA li na le lihokelo tsa li-anatomical (Simon et al. 1979). Merero ea VTA ka kotloloho ho LC mme e kanna ea lokolla DA moo, e bonts'ang kamano e kopaneng pakeng tsa VTA le LC (Ornstein le al. 1987; Sara 2009). Ho feta moo, VTA e ka susumetsa ts'ebetso ea PFC ka ts'ebeliso ea DA hore e fetole ts'ebetso ea methapo ea LC ka tokollo ea glutamate (Sara 2009), le li-neuron tsa VTA DA li fetoloa ka noradrenaline e lokolloang ka lebaka la ts'usumetso ea motlakase oa LC (Grenhoff et al. 1993). Lipatlisiso tsa lesions tsa li-neuron tsa LC noradrenaline le li-neurons tsa VTA DA li fana ka maikutlo a hore LC noradrenaline neurons le VTA DA neurons li na le tšusumetso e thibelang methapo ea DA ho thunya ho VTA le li-neuron tsa methapo ea methapo ho LC, ka ho latellana (Guiard et al. 2008). Leha ho le joalo, α1-receptor antagonism e entsoeng ke prazosine ho LC e senotse ho fokotseha ha ho thunya ha neuron ho VTA, ho fana ka maikutlo a phello e thabisang ea LC noradrenaline neurons ho li-neurons tsa VTA DA le (Grenhoff le Svensson 1993). Kahoo, LC e etsa puisano e rarahaneng e sebetsang le VTA.

Ka bobeli LC (Vankov et al. 1995) le VTA (Schultz et al. 1993) li-neurons li qaptjoa ke lipalesa, li sebetsa e le lipontšo tsa ho ithuta ka mokhoa o tlatselletsang (Harley 2004). Athe LC e qala ho sebetsa hang ha ho qala boiphihlelo (Aston-Jones le Bloom 1981; Sara le al. 1994), VTA e qala ho sebetsa nakong ea li-millisecond tse makholo hamorao (Ljungberg et al. 1992). Sena se fana ka maikutlo a hore LC, ebang ke ka puisano e tobileng le VTA, kapa ka hippocampus-VTA loop, e ka laola ho lokolloa ha DA ho tloha VTA ho ea hippocampus. Tumellanong le monyetla ona, li-receptors tsa D1 / D5 li kentse letsoho ho laola hippocampal LTD e khothalletsoang ke ts'usumetso ea LC (Lemon et al. 2009; Lemon le Manahan-Vaughan 2011). Mona, D1 / D5 antagonism e thibela LC-CA1 LTD. Ntle le moo, ts'ebeliso ea agonist ea d1 / D5 receptor e nolofalletsa LC-e thehiloe CA1 E-LTD ho L-LTD e nka nako e fetang 24 h (Lemon le Manahan-Vaughan 2011; Tafole 1B). Liphumano tsena li fana ka maikutlo a hore sistimi ea li-receptor ea D1 / D5 e sebeletsa ho theola monyako o hlokahalang bakeng sa ho boloka tlhaiso-leseling ea litaba tlasa maemo a bocha kapa ho eketseha hoa thabo ho sa tsotelehe mohloli oa ponts'o e sa tloaelehang (Lemon le Manahan-Vaughan 2011).

Eya ho:

D1 / D5 Receptors ke Phokotso ea ho Boloka Tlhahisoleseling ea Hippocampal

Ho ipapisitsoe le tsebo ea hona joale, ho hlakile hore li-receptors tsa D1 / D5 li bapala karolo e makatsang le e makatsang ho thuseng ha khokahanyo ea tlhahisoleseling le polokelong ea hippocampus. Ba ka tsamaisa polelo ea bobeli ba LTP le LTD, mme ba ela hloko bopaki bo bokelletseng ba hore PDP e kenyelletsa likarolo tse fapaneng tsa boemeli ba sebaka (Kemp le Manahan-Vaughan 2007, 2008a; Goh le Manahan-Vaughan 2012), sena se fana ka maikutlo a hore li-receptor tsa D1 / D5 li ka tsamaisa mofuta le litekanyetso tsa tlhahisoleseling tse bolokiloeng hippocampus. Ka mokhoa o makatsang, motheong o sebetsang mme o tsamaellana le seteraeke sena, ts'ebetso ea li-receptor tsa D1 / D5 e lebisa tšebetsong e eketsehileng ka har'a potoloho ea "trisynaptic DG-CA3-CA1", ho isa tsietsing ea tlatsetso ea entorhinal-CA1 ka kotloloho.Varela et al. 2009), ka tsela eo, fokotsa khatello ea ts'ebetso ea ho se bone hantle (Lismann le Otmakhova 2001) molemong oa ho beha polokelong ea tlhaiso-leseling. Sena le sona se kanna sa sebetsa haholo ha ho kopanngoa le polokelo ea litaba le mohopolo ka boiphihlelo ba moputso.

Ho nka hammoho le tlhokomeliso ea hore D1 / D5 receptor activation modulates ea episodic e itšetlehileng ka nako e telele, lintlha tsena li bonts'a hore D1 / D5 receptors gate hippocampal ea nako e telele le memori bokong ba mammary, ebile li bohlokoa ho fetisa mokokotlo. thepa ea bohlanya le moputso ho tlhahisoleseling e ntseng e sebetsoa ke hippocampus.

Eya ho:

dithuso tsa ditjhelete

Mosebetsi ona o tšehetsoa ke chelete ea thuso e tsoang motheong oa lipatlisiso tsa Jeremane (Deutsche Forschungsgemeinscaft, www.dfg.de) ho Denise Manahan-Vaughan (Ma1843 / 6-2).

Eya ho:

Notes

Khohlano ea ThahaselloHa ho ea phatlalalitsoeng.

Eya ho:

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