Karolo ea lateral hypothalamus le orexin ka boits'oaro bo botle: mohlala bakeng sa phetolelo ea phihlelo ea nakong e fetileng le ho lemoha mefokolo ka boitšoaro bo susumelletsang (2014)

Pele Syst Neurosci. 2014 Nov 13; 8: 216. Doi: 10.3389 / fnsys.2014.00216. eCollection 2014.

Hurley SW1, Johnson AK2.

inahaneloang

Hypothalamus e ananetse ho kenya letsoho ha eona ho bolokeng homeostasis le litekanyetsong tsa boitšoaro bo susumetsang. Sengoloa sa hona joale se tšohla sebaka sa hypothalamus se tsejoang ka sebaka sa morao sa hypothalamic (LHA). Ho khothalletsoa hore boko ba kelello kahare ho LHA ​​ho kenyelletsoa le sebaka sa dorsal sa lateral hypothalamus (LHAd) le sebaka se poteletseng (PeF) se fane ka khokahano lipakeng tsa lits'ebetso tsa neural tse laolang homeostasis le tseo boeletsi bo khothalletsang boitshwaro bo khothalletsang boitšoaro. Lintlha tsa ts'ebetso le immunohistochemical li bonts'a hore LHA e khothaletsa boitšoaro bo bongata bo susumetsang bo kenyeletsang ho ja lijo, ho ja metsi, ho ja letsoai le boitšoaro ba thobalano.. Liteko tsa ho batla tsa Anatomical li bonts'a hore LHA e maemong a ho amohela litlatsetso tse tsoang libakeng tsa boko tse kenyelletsang ho laola mokelikeli oa 'mele le homeostasis ea matla. Libaka tse fumanehang kahare ho LHA ​​li romella lits'oants'o tse matla sebakeng sa "ventura tegmental" (VTA), e fana ka tsela bakeng sa LHA ea ho susumetsa lits'ebeletso tsa dopaminergic ka kakaretso tse amoheloang ho nka karolo boits'oarong bo matla le tšebetsong ea bona. Ntle le moo, LHA e na le li-neuron tse kopanyang orexin / hypocretin, e leng neuropeptide e khothalletsang boits'oaro bo bongata ba takatso ea takatso. LHA e boetse e amohela lipehelo tse tsoang libakeng tsa boko tse nkang karolo ho ithuteng tse amanang le moputso le ts'ebetso ea methapo ea kutlo ea orexin e ka ba boemo ba tšusumetso ea tikoloho e amanang le meputso. Ka hona, hoa tšelisoa hore LHA e kenyeletsa ho supa libakeng tse laolang phallo ea 'mele le botsitso ba matla le thuto e amanang le moputso. Ka lehlakoreng le leng, leseli lena le "feptjoa ho" mesolimbic circry ho susumetsa ts'ebetso ea boits'oaro bo susumetsoang. Motsoako ona o ka khothaletsa liteko tse tla etsa hore ho be le kutloisiso e ntlafalitsoeng ea ts'ebetso ea LHA. Kutloisiso e ntlafalitsoeng ea ts'ebetso ea LHA e ka thusa ho phekola maloetse a amanang le ho nona kapa ho senyeha ha polelo ea boits'oaro ba ho ts'oara ho kenyelletsa botenya, ho ipolaisa tlala, ho sitisoa ke lenyora, ho jeoa ke letsoai le khaello ea letsoai.

Keywords: tšusumetso, homeostasis, hamorao hypothalamus, neural plasticity, takatso ea letsoai, lenyora, ho ja lijo, orexin

Selelekela

E le hore u pholohe liphoofolo li tlameha ho boloka matla le fluid homeostasis. Likhalori li lula li lahleha ka mekhoa e bolokang bophelo ba mantlha le ka lebaka la boits'oaro. Ka mokhoa o ts'oanang, liphoofolo tsa lefats'e li lula li lahleheloa ke metsi le sodium ho ea tikolohong ka lebaka la ts'ebetso e tloaelehileng ea 'mele le tikoloho ho kenyelletsa ho phefumoloha, ho fetella, ho ruruha, ho ruruha le ho senyeha. Maemo a mang a sa tloaelehang a kotsi e kholo ho matla le ho mokelikeli oa 'mele homeostasis. Mohlala, ho kula ho ka etsa hore motho a felloe ke matla a ho bolaoa ke lets'ollo le ho hlatsa tse felisang 'mele metsi le sodium. Hang ha mmele o se o na le likhalase, metsi, kapa sodium ho bohlokoa hore phoofolo e fumane lintho tse e jang tikolohong ho khutlisetsa homeostasis.

Tsamaiso ea methapo e bohareng e hlahisa linaha tse susumetsang ho khothaletsa ho batla le ho monya ha lintho tse tikolohong. Boemo bo susumetsang ba tlala, kapa ho batla le ho ja lijo, hoa hlokahala bakeng sa phoofolo ho khutlisa bofokoli ho matla homeostasis. Takatso ea lijo le lenyora la sodium (hape e tsejoang e le [AKA] takatso ea letsoai), kapa ho fumaneha ha metsi le sodium, hoa hlokahala ho khutlisetsa tekanyo ea mokelikeli. Mebuso ena e susumetsoang e tsamaea le lits'ebetso tsa methapo ea methapo e matlafatsang boitšoaro (ke hore, e hlahisa boemo ba kelello bo hlasimollang le ho khothaletsa boitšoaro ba locomotor) le ho khothaletsa boitšoaro bo tataisoang ke sepheo (Bindra, 1959; Bolles, 1975). Ho bonts'itsoe hore linaha tse ngata tse susumetsang li tsamaisana le phetoho ea hedonic moo likarabo tse khahlisang kapa tse nyarosang tse hlahisoang ke ts'usumetso e itseng li ntlafalitsoeng kapa li thibetsoe (Garcia et al., 1974; Fanselow le Birk, 1982; Berridge et al., 1984; Mehiel le Bolles, 1988; Berridge le Schulkin, 1989). Mohlala, ha litoeba tse nang le sodium-replete li fumana infusions tse tsoang kahare tsa tharollo ea letsoai le matla li bontša likarabo tse ikhethileng tsa boits'oaro tse bonts'ang mofetoheli (Grill le Norgren, 1978; Berridge et al., 1984) le litoeba tse nang le sodium e phetseng hantle li tla sesa litharollo tsa letsoai le leholo (Robinson le Berridge, 2013). Leha ho le joalo, ha likhoto li haelloa ke sodium li bonts'a mekhoa ea tloaelo ho tharollo ea letsoai mme li tla etsa likarabo tse bohlokoa ho fumana likarabo tsa sodium (AKA opereishene; Berridge et al., 1984; Clark le Bernstein, 2006; Robinson le Berridge, 2013). Tlas'a maemo a haelloang ke sodium ba bile ba bontša likarabo tsa boitšoaro tse bonts'ang thabo ho e-na le ho tsilatsila ha litharollo tsa letsoai la hypertonic le kenngoa kahare (Berridge et al., 1984). Ka mokhoa o ts'oanang, batho ba lekanya lijo tse letsoai haholo ho feta ha li na le sodium e fokolang (McCance, 1936; Beauchamp et al., 1990).

Mebuso e susumetsang ea tlala, lenyora, le takatso ea letsoai li susumetsoa haholo ke boemo ba phoofolo ba matla le boits'oaro ba metsi (ke hore, homeostatic state). Hoa utloahala ho kenyelletsa lisebelisoa tsa neural tse hlokometseng matla le phallo ea homeostasis e le lits'ebetso tsa maikutlo ka tokelo ea bona. Mabapi le ho leka-lekana ha matla, khubu ea arcuate ea hypothalamus (ARH) e amohetse tlhokomelo e kholo bakeng sa karolo ea eona ea ho utloa matšoao a pherekano a amanang le tlala le ho satiety (Schwartz et al., 2000). Li-ensemble of forebrain nuclei e lutseng haufi le lamina terminalis (LT) li bohlokoa bakeng sa ho fumana lipontšo tse amanang le boemo ba mokelikeli oa 'mele (Denton et al., 1996; Johnson le Thunhorst, 1997). Meaho e ikhethileng e haufi le LT ke karolo ea subfornical organ (SFO), sebaka sa "Medium preoptic" (MnPO), le organum vasculosum ea lamina terminalis (OVLT). Ho thusa ho hlakisa meaho ena ho bokana hammoho ho thoe ke LT. SFO le OVLT ke litho tsa kelello tse potileng, kapa libaka tsa boko tse se nang tšitiso ea 'nete ea mali (Johnson le Gross, 1993) e ba lumellang ho lekola lintho tse maling tse sebetsang e le lipontšo tsa boemo ba mokelikeli ba mmele (Johnson le Thunhorst, 1997, 2007). Ho bohlokoa hape ho tseba mona hore hona joale ho na le ngangisano ea hore na ARH e haelloa ke tšitiso ea mali le mali mme ke karolo ea 'nete e potileng (Mimee et al., 2013). Kahoo, ho bile le tlhahiso ea hore LT e ka sebetsa hape ho fumana lipontšo tse amanang le tekanyo ea matla (Mimee et al., 2013; Smith le Ferguson, 2014).

Ho bohlokoa ho hlokomela hore ho kenella ha lijo, metsi le sodium ho hloka tšebetso e hokahaneng pakeng tsa lipotoloho tsa neural tse utloang matla le boemo ba mokelikeli le potoloho ea neural e kenyelletsang ho susumetsa boits'oaro bo susumetsang (Garcia et al., 1974;; Roitman et al., 1997; Kelley le Berridge, 2002; Liedtke et al., 2011). Ka hona, likarolo tsa bokong tse lekolang boemo ba mokelikeli le boemo ba matla li tlameha ho kenella libakeng tse laolang tšusumetso le moputso. Tsela e 'ngoe ea ho qetela e tloaelehileng e amehang molokong oa mekhoa eohle ea takatso ea takatso ea lijo e ntseng e phenyekolloa ho fihlela joale ke ea projeke ea dopaminergic ho tloha sebakeng sa ventral tegmental (VTA) ho ea ho li-nucleus accumbens (AKA sa mesolimbic dopamine system le sehlopha sa lisele tsa A10 dopaminergic; Mogenson et al. ., 1980; Bozarth, 1994). ARH le LT, tse amehang ho fumaneng matla le phallo ea mokelikeli, ha li bonahale e le kahare ho VTA (Phillipson, 1979; Geisler le Zahm, 2005; leha ho le joalo ARH e kenella ka kotloloho ho li-nucleus bokello; Yi et al., 2006; van den Heuvel et al., 2014). Kaha ha ho na likhakanyo tse tobileng ho VTA ho ka etsahala hore libaka tsa hypothalamus li ka thusa ho "koala lekhalo" pakeng tsa homeostasis le ts'usumetso le tsamaiso ea meputso (Mogenson et al., 1980; Swanson le Mogenson, 1981; Swanson le Lind, 1986). Mohlala, lithuto tsa ho batla morao-rao li bontšitse hore sebaka se seholo sa hypothalamus se na le li-neurons tse projeke e eang ho VTA (Geisler le Zahm, 2005). Setereke sena se tloha ho dorsomedial hypothalamus (DMH) ho ea sebakeng sa dorsal sa lateroth hypothalamus (LHAd) mme se bonahala se le teng ho pholletsa le boemo bohle ba ka morao ba hypothalamus.

Bopaki bo tšehetsang karolo ea LHA ho kopanya mmuso oa homeostatic le litsamaiso tsa khothatso le moputso

Ka pampiri ea khale, Stellar (1954) e hlahisitse mohopolo oa tšusumetso ea hypothalamus. Stellar o ile a fana ka maikutlo a hore hypothalamus e na le "litsi" tseo ka tloaelo li arohaneng mme setsi ka seng se phethile karolo ea bohlokoa ho holiseng boits'oaro bo itseng bo susumetsoang. Mohlala, o bontšitse hore hypothalamus e na le litsi tse laolang ka kotloloho thobalano, satiety, tlala le boroko. Tlhahiso ea Stellar e fumane tlhahlobo e hlokolosi ea liteko mme e fumanoe e sa lekana ho hlalosa data e hlahang (Miller et al., 1964; Miller, 1965; Hoebel le Teitelbaum, 1966; Booth et al., 1969). Leha taba ea hore khopolo ea Stellar e oele e hlakisa karolo ea hypothalamus ka boits'oaro bo itseng bo khothalletsoang, bopaki bo nahanang bo bontša hore libaka tse kahare ho hypothalamus li hlile li bapala karolo ea bohlokoa ho holiseng boits'oaro bo khothalletsoang ba bohloeki ka kakaretso.

Liteko tsa khale tse sebelisitseng likhahla tse nyane tsa ts'usumetso ea motlakase tse lebisitsoeng sebakeng sa morao sa hypothalamic (LHA) li bonts'itse hore LHA e kentse letsoho lits'ebetsong tsa khothaletso le moputso. Ba baholo le ba Milner (1954) ea mantlha e fumane hore likhoto li tla etsa moetsi ho fumana ts'usumetso e matla ea motlakase ea LHA, e leng tlhahlobo ea tlhahlobo ea linako tse ling eo ho thoeng ke ea ho ikhatholla kapa ea ho khothatsa moputso. Ba fetoletse ho fumana ha bona ho bolela hore tšusumetso ea motlakase ea LHA e-na le moputso (ke hore, tšusumetso ea LHA e ile ea tsosa mofere-fere). Haeba tlhahlobo ena e nepahetse, ho ka khothaletsa hore li-neuron tse ling ka har'a LHA li bohlokoa ka mokhoa o nepahetseng bakeng sa ho khabisa litlatsetso ho tsoa ho tšebeliso ea meputso. Leha ho le joalo, ba bang ba boletse hore tšusumetso ea LHA e kanna ea hlahisa maemo a ho lakatsa ho e-na le ho ithabisa ka bobeli (Berridge le Valenstein, 1991). Haeba tlhaloso ena e le 'nete e ka fana ka maikutlo a hore karolo e ka tlase ea li-neuron tse fumanehang ho LHAd e kenelletse takatsong e khannelang liphoofolo ho fumana meputso. Ho ka etsahala hore thepa e susumetsang le e khotsofatsang ea tšusumetso ea LHA e hlahisoe ke ts'ebetso ea li-neurons ho LHA ​​morero ona ho sisteme ea mesolimbic dopamine system (Phillipson, 1979; Geisler le Zahm, 2005). Liteko tsa morao-rao tse sebelisang 'mapa oa "hedonic hotspots", kapa libaka tsa boko tse shebahalang li thabisa khoutu (Peciña le Berridge, 2000), bonts'a hore li-neuron tse sebakeng sa projeke ea LHA ho ea hotspot ea hedonic e ka har'a dorsomedial nucleus accumbens shell (Thompson le Swanson, 2010), mme ho ka etsahala hore tšusumetso ea LHA e ka etsa hore li-neuron tsena tsa projeke li tsose mohopolo oa thabo. Ho khahlisang, haeba LHA e hlohlelletsoa nako le nako hore e be litoeba tse lekaneng (~ 10-30 s) e tla etsa boits'oaro bo khothalletsoang ho kenyelletsa ho noa, ho ja le boits'oaro bo kopanetsoeng (Wise, 1968). Ntle le moo, marang-rang a LHA a felisa tšebeliso ea lijo le metsi, ho li qopitsa le ho fokotsa takatso ea lijo ea sodium (Anand le Brobeck, 1951; Montemurro le Stevenson, 1957; Teitelbaum le Epstein, 1962; Wolf, 1964; Wolf le Quartermain, 1967; Cagguila et al., 1973; Grossman et al., 1978; Hansen et al., 1982).

Ho sitisoa ke matla le ho feto-fetoha ha tekanyo ea mokelikeli ho arabela bakeng sa ho intlafatsa (Olds, 1958; Morris et al., 2006, 2010). Maqheku (1958) qalong o fumane hore likhoto tse fokotsang lijo le ho susumetsa boemo ba tlala ba tlala ho eketsa ho arabela bakeng sa ho ikhatholla. Ntle le moo, ho arabela ka mokhoa o eketsehileng bakeng sa ho itlhasimolla nakong ea ho hloka lijo ho ka thibeloa ke tsamaiso ea leptin, e leng hormone e khothalletsang satiety (Fulton et al., 2000). Ho fapana le khaello ea lijo, ho fokotsoa ha sodium ho fokotsa ho arabela bakeng sa ho intlafatsa (Morris et al., 2010). Phokotso ea ho arabela bakeng sa ho itlhasimolla le ho bonoa ha likhoto li etsoa letsoai le lapile ka tsamaiso ea lihormone tse tsoetseng pele tse khothalletsang takatso ea letsoai; leha ho le joalo le likhoto li boloka sodium e leka-lekaneng nakong ea kalafo ena (Morris et al., 2006). Ha ho hlake hore na ke hobaneng ha linaha tse susumetsang tsa tlala le takatso ea letsoai li hlahisa litlamorao tse tlatselletsang molemong oa ho ikhatholla. Leha ho le joalo, lithuto tsena li bonts'a hore tlala le letsoai la takatso ea lijo li iphetola ka mokhoa o ikhethileng mme phello ena e bonahala e ikemetse ka thipa ea tšitiso ea 'nete ea matla kapa mokelikeli oa ntlo. Mohlala, leptin e tloaela ho itšireletsa e arabela ntle le ho lokisa likhalori tse lahlehileng (Fulton et al., 2000) le ho ikarabela ho itšunya-tšunya ho ka fokotsoa ka ho qhekelloa ho theosetsang tlala ea letsoai ntle le ho kenyelletsa khaello ea sodium (Morris et al., 2006). Habohlokoa, liteko tsena li tšehetsa tšibollo ea hona joale ka ho bonts'a hore LHA e tsotella boemo ba phoofolo bo susumetsang.

Bo bong ba bopaki bo matla ka ho fetisisa bo tšehetsang karolo ea hypothalamus ho khothaletsa boitšoaro bo susumetsoang bo tsoa ho lithuto tse hlahlobang orexin (AKA hypocretin). Orexin ke "neuropeptide" e hlahisoang haholo karolong ea caudal ea hypothalamus moo e ajoang ka arc e tlohang ho DMH ho ea ho LHAd (Setšoantšo. (Figure1) .1). Orexin e bonahala e le ona feela tsamaiso e tsebahalang ea peptide neurotransmitter e le li-neuron tsa orexin tse tsoang sebakeng se batlang se le sephara se romella lits'oants'o tsa distal libakeng tse fapaneng tsa boko (Peyron et al., 1998). Ka mokhoa o sebetsang, li-neuron tsa orexin li kentsoe haholo linthong tse fapaneng tsa boitšoaro bo khothalletsoang (Harris et al., 2005; Borgland et al., 2009). Orexin e amohetse tlhokomelo e kholo bakeng sa bokhoni ba eona ba ho etsa hore ho nkoe lijo tse matla (ka hona lebitso orexin; Sakurai et al., 1998; Choi et al., 2010) empa e kenelletse ho nts'etsapele lenyora, takatso ea letsoai (Kunii et al., 1999; Hurley et al., 2013a), le boitšoaro ba ho ba le bana (Muschamp et al., 2007; Di Sebastiano et al., 2010). Li-neuron tsa Orexin li ka hlophisoa ka mokhoa o hlophisitsoeng hore e be lihlopha tse tharo tsa lisele ho hypothalamus: sehlopha sa DMH, sebaka sa pherekano (PeF), le LHAd (Setšoantšo. (Figure1) .1). Ka bobeli PeF le LHAd ke litereke tse ho LHA ​​ha DMH e lutse kahare moo e sebelisang mochini oa boraro. Sehlopha se seng le se seng sa orexin se na le karolo ea li-neuron tsa orexin tse projeke ho VTA (Setšoantšo. (Figure1; 1; Fadel le Deutch, 2002), mme orexin e khona ho nyenyefatsa li-neuron ho VTA (Korotkova et al., 2003). Ka hona, li-neuron tsa orexin li fana ka mokhoa oa libaka bakeng sa libaka tsa LHA ho kenya lits'ebetsong tseo ka tloaelo li nkiloeng e le karolo ea tšusumetso le moputso. Bopaki bo boetse bo bonts'a hore li-neuron tsa orexin li na le menahano e otlolohileng ka kotloloho ho khubung ea li-nucleus accumbens (Peyron et al., 1998; Kampe et al., 2009) moo ba ka nkang bohato ba ho khothaletsa boitšoaro bo susumetsang (Thorpe le Kotz, 2005).

Setšoantšo sa 1 

Lintlha tse sa phatlalatsoang ho tsoa ho bangoli. Ho tsamaisana pakeng tsa li-neuron tsa orexin le VTA ho hypothalamus. Fluoro-Gold (Fluorochrome, Denver CO) ea morao-rao e ne e fokotsoe (2% ho 250 nl) ho VTA, mehopolo e ne e bokelloa le ho sebelisoa ha 40µm, ...

Mesebetsi e meng e meholo ea orexin e kenyelletsa ho ntšetsa pele ho tsosa takatso ea motho (Hagan et al., 1999) le likarabo tsa tsamaiso ea methapo e nang le kutloelo-bohloko tse kenyeletsang ho phahama ha khatello ea mali (Samson et al., 1999; Ferguson le Samson, 2003; Kayaba et al., 2003) le tokollo ea lihormone tsa khatello ea maikutlo (Kuru et al., 2000; Spinazzi et al., 2006). Ho ka etsahala hore li-neuron tsa orexin li sebetse ha phoofolo e ntse e e-na le bothata ba caloric, hydrational kapa sodium kapa e le boemong ba ho tsosa takatso ea thobalano. Ho lokolloa ha morao ha orexin ho pholletsa le neuraxis ho khothaletsa ts'ebetso ea boits'oaro bo tataisitsoeng ka sepheo sa ts'ebetso ea ts'ebetso ea ts'ebetso ea ts'ebetso ea methapo e kenyelletsang molemong oa ho tsosa moferefere, tlhokomelo, ts'ebetso ea kutloelo-bohloko, le boitšoaro bo susumetsang. Ts'ebetso ea kutloelo-bohloko e ts'ehetsa ho bokella matla (mohlala, khatello ea mali e eketsehang le litekanyetso tsa glucose tse teng, le tokollo ea lihormone) le phano ea mali e hlokahalang ho ts'ehetsa ts'ebetso e eketsehileng ea locomotor. Ha li kopane likarabo tsena tse bohareng le tse matla li eketsa monyetla oa hore phoofolo e atlehe ho batla le ho sebelisa matlafatso a tikoloho a khutlisetsang matla le motlakase oa homeostasis.

Lithuto tsa Anatomical le immunohistochemical li ts'ehetsa mohopolo oa hore LHA e thusa ho hokahanya ho saena ho tsoa ho li-peptides tsa orexigenic tse nang le li-neurocircuitry tse kenyelletsang tšusumetso le moputsong. Neuropeptide Y (NPY) e hlahisoa ka li-neurons tsa ARH (Hahn et al., 1998) le neuropeptide ena e etsa hore motho a fepe (Schwartz et al., 2000). Ho khahlisang, li-neuron tsa NPY li romela likhakanyo tse matla tse ntseng li sebetsa le li-neuron tsa orexin tse fumanehang ho LHA ​​(Broberger et al., 1998). Mekhoa ea kalafo e bakang tlala e kang hypoglycemia kapa tsamaiso ea li-peptide tsa orexigenic ho kenyelletsa ghrelin le NPY ho ts'oara c-fos expression in orexin-tseka li-neurons (Moriguchi et al., 1999; Niimi et al., 2001; Toshinai et al., 2003). Ho kenyelletsa moo, ho senya orexin neurotransmission e kenyelletsa ho fepa ho susumetsoang ke tsamaiso ea NPY kapa ghrelin. Li-Neurons tse sebakeng sa dorsomedial ARH, e leng sebaka sa ARH se nang le li-neuron tse ngata tsa NPY, le tsona li etsa projeke ea PeF mohlomong le LHAd (Setšoantšo. (Figure2; 2; Hahn le Swanson, 2010).

Setšoantšo sa 2 

Lintlha tse sa phatlalatsoang ho tsoa ho bangoli. Retrograde labelling ho tloha LHAd le PeF ho ea ho LT le arcuate nucleus ea hypothalamus. 2% Fluoro-Khauta ho saline ea 'mele e ne e qoelitsoe ho PeF le LHAd (A). Retrograde labeling e bonoe ho pholletsa le ...

Ho fapana le lithuto mabapi le lijo, ha ho na mosebetsi o fokolang o entsoeng ho hlalosa hore na LT e ka ba le tšusumetso e joang le ho putsa maqhubu a ho potoloha. Ho bonahala eka LT ha e bue ka ho toba ho VTA (Phillipson, 1979; Geisler le Zahm, 2005) kapa li-nucleus accumbens (Brog et al., 1993), empa, ka tsela tse ling, tse khahlisang le ho sebetsana le tlhaiso-leseling e amanang le mokelikeli oa 'mele oa homeostasis e tlameha ho ts'oara le ho putsa li-neurocircuitry. SFO e bontšitsoe hore e romella lits'oants'o ho DMH, PeF, le LHAd (Swanson le Lind, 1986; Hurley et al., 2013a). Ntle le moo, liteko tsa morao-rao ka laboratoring ea rona li bonts'itse ts'ebeliso ea iontophoretic ea "trluer-tracer" ea morao-rao karolong ea bokantle ea DMH, PeF, 'me LHAd e senola ho ngola ka morao ho potoloho eohle ea enjene. hasanngoa ho tloha PeF ho ea LH e hlahisoa ka Setšoantšo Figure2) .2). Ba bang ba bonts'itse hore PeF e amohela likhakanyo tse tsoang ho botlalo ba LT (Hahn le Swanson, 2010). Ho ekelletsa moo, haufinyane re fumane hore li-neuron tsa orexin li sebetsa ha likhoto li felisitsoe ke metsi le sodium li lumelloa ho kenella metsi le hypertonic saline le hore microinjection ea orexin receptor antagonist ho VTA e kopaneng ea metsi le ho kenella ha sodium ho likhoto tse felileng (Hurley et al ., 2013a). Ka hona, ho ka etsahala hore projeke ea projeke ho DMH, PeF le LHAd, ebe, e romelle merero ea orexinergic ho VTA. Ho lokolloa ha Orexin ho VTA ho khothalletsa ho kenella ha metsi le sodium. Liteko tsena li fana ka tšehetso ea tšebetsong le ea tšebetso ho khopolo ea hore LHA e kopanya leseli mabapi le naha ea homeostatic ka lits'usumetso tsa meputso le moputso.

Bopaki bo tšehetsang karolo ea LHA thutong e amanang le moputso

Litlhahlobo tse ileng tsa hlahloba phello ea ho hlohlelletsa hoa LHA ho boits'oarong bo susumetsang li fane ka bopaki bo bong ba pele ba hore LHA e ka nka karolo ho ithuteng ho amanang le moputso. Ha litoeba ka bomong li fumana tšusumetso ea LHA qalong li bonts'a boitšoaro bo ikhethang bo susumetsang (Valenstein et al., 1970). Likhoto tse ling li tla ja, ha tse ling li tla noa kapa li etsa boitšoaro bo bobe. Boitšoaro bo susumetsang ba Rate e 'ngoe le e' ngoe bo kenella bo bitsoa boitšoaro ba pele ho pele. Habohlokoa le ho feta, boitsoaro ba pelehi bo entsoeng nakong ea ts'usumetso ea LHA bo ka fetoloa ka boiphihlelo (Valenstein et al., 1970). Haeba sepheo sa sepheo se khethiloeng se tlosoa nakong ea ts'usumetso ea LHA, likhoto li tla lebisa boits'oarong ba tsona ho ea ho ntho e 'ngoe e teng tikolohong. Mohlala, haeba mokokotlo o ja nakong ea ts'usumetso ea LHA, lijo li ka tlosoa ha spout e ntse e noella. Maemong ana, morethetho o khothalelitsoeng o tla nooa hona joale ke spout. Habohlokoa, ha LHA e hlohlelletsoa litekong tsa nako e tlang ha lijo le metsi li le teng, rat e tla arola nako ea eona lipakeng tsa ho ja le ho noa. Ka hona, ho ts'oara ho ts'oaroa ha LHA le ho ba teng hoa ntho eo pele e neng e sa khethoe ho etsa hore rat e lebise boits'oaro ba eona nthong ea sepheo e neng e sa tsotelloe pele. Ho bonahala eka tšusumetso ea LHA le tšebeliso e latelang ea ntho ea sepheo li hlahisa sebopeho sa thuto e kopaneng e hlahisoang ka liphetoho mekhoeng ea boitšoaro ba pele.

Orexin neuron e sebetsang e ka ba boemo ba ho hlohlelletsa tikoloho. Sebakeng se khethiloeng paradigms pale e potolohileng ea tikoloho e amahanngoa le moputso. Kamora ho pheta-pheta taba e potolohileng tikoloho ka moputso, likhoto li tla bonts'a khetho ea moelelo o katiloeng ka moputso. Khetho e ntseng e hlaha maemong a khethollo ea libaka e bonahala e amana le ts'ebetso ea orexin neuron. Li-neuron tsa Orexin li hlahisa c-fos ho arabela maemo a tikoloho a amanang le lithethefatsi tsa tlhekefetso le thobalano (Harris et al., 2005; Di Sebastiano et al., 2011). Ntle le moo, lesioning orexin neurons e nang le orexin e kopaneng-saporin e thibela likhoto tsa banna ho bontša sebaka sa maemo a ratang boemo ba tikoloho bo amanang le kopi (Di Sebastiano et al., 2011).

Bopaki bo bong bo tšehetsang karolo ea LHA ho kenya letsoho mefuteng ea thuto ea moputso bo tsoa mohloling oa ho fepa ka sepheo sa cue. Pararigm e kentsoeng ke cue e khothalletsoang ke lijo, likhoto tse haelloang ke lijo li lumelloa ho ja ka pel'a setopo sa tikoloho. Cue ena ha e le hantle e fetoha tšusumetso e nang le maemo (CS +) e khonang ho susumetsa takatso ea lijo. Ha CS + e hlahisoa ho litoeba, leha li le maemong a tsitsitseng, li tla qala ho ja (Petrovich et al., 2007). Ho khahlisang, likhoto li tla ja feela bongata ba lijo tse ikhethileng tse nang le CS +, empa eseng lijo tse tloaelehileng kapa tse tloaelehileng (Petrovich le Gallagher, 2007). Ka hona, ho bonahala eka tlhahiso ea CS + e tsosa takatso e khethehileng ea lijo tse pakiloeng ka CS +, ho fapana le tlala ka bobeli. LHA ke sebaka se seng se bohlokoa bakeng sa ts'ebetso ea phepo e tsoang ho cue-Petrised (Petrvich le Gallagher, 2007; Petrvich et al., 2005). LHA e fumana litlatsetso tse tsoang libakeng tse amehang ho mefuta ea ho ithuta ka moputso ho kenyeletsoa amygdala (Krettek le Price, 1978; E-et et al., 1999) le cortex ea pele (Gallagher et al., 1999). Li-Neurons tseo projeke e eang ho LHA ​​ho tloha basolateral / basomedial amygdala le orbitomedial preortal cortex e hlahisoa ho arabela tlhahiso ea CS + (Petrovich et al., 2005). Ntle le moo, lesapo la mokokotlo la semmuso la li-amygdala tsa basolateral le LHA li thibela ho feptjoa ha cue-ikiwa (Petrovich et al., 2005). Orexin o bonahala a bapala karolo ea phepo e tsoang ho cue-ha litoeba li pepesoa ke CS + li hlahisa haholo c-fos li-neurons tse ntle tsa orexin ho PeF (Petrovich et al., 2012).

Kamora nako, LHA e kentsoe mofuteng o sa amaneng le thuto e amanang le moputso. Ha likhoto li felisoa ka sodium khafetsa li bonts'a keketseho ea tekanyo ea sodium (Falk, 1965; Sakai et al., 1987, 1989), ketsahalo e reng e khothatsa takatso ea sodium (Hurley et al., 2013b). Sensitization ea takatso ea sodium e kanna ea ba mofuta oa thuto e sa amaneng le (Falk, 1966; Frankmann et al., 1986) e itšetlehileng ka glutamatergic NMDA receptor-neural plasticity (Hurley le Johnson, 2013). Bopaki bo fana ka maikutlo a hore takatso ea takatso ea sodium e kenyelletsa polasetiki ea neural ho potoloho e 'meli ea neural: potoloho e le' ngoe e tsamaisang 'mele oa homeostasis le tšusumetso e' ngoe ea potoloho le moputso (Roitman et al., 2002; Na et al., 2007). c-fos polelo e susumetsoang ke ho theoha ha sodium e phahamisitsoe ho likhoto tse nang le nalane ea ho theoha ha sodium ho SFO, basolateral amygdala, medial prefrontal cortex, le li-bokellos tsa nucleus ha li bapisoa le litoeba tse se nang nalane ea ho theoha ha sodium (Na et al., 2007). Ntle le moo, likhoto tse nang le nalane ea sodium depletions li bonts'a ntlafatso ea dendritic arborization le bolelele ba li-nucleus accumbens (Roitman et al., 2002). Libaka tse ngata tse shebahalang li khahlisoa ke nako ea ho theoha ha sodium le tsona li romella likhakanyo ho LHA, ho kenyelletsa SFO, preortalal cortex, le basolateral amygdala. LHA e romela likhakanyo ho VTA, eo le eona e khonang ho ts'oara polasetiki ea neural ho li-nucleus accumbens neurons (Mameli et al., 2009). Qetellong, bopaki bo eketsehileng bo tšehetsa monyetla oa hore li-neurone tsa orexin li latsoehe ka har'a neural ho tloha sodium depletion (Liedtke et al., 2011). Protheine e amanang le tšebetso ea cytoskeleton e amanang le tšebetso, e phethang karolo ea bohlokoa ho polasetiki ea neural (Tzingounis le Nicoll, 2006; Molisa le Beere, 2011), e ngolisitsoe ka har'a li-neuron tsa PeF orexin nakong ea ho theoha ha sodium (Liedtke et al., 2011).

Khopolo-taba le liqeto

Liteko tse hlahlojoang li tšehetsa tšusumetso eo LHA ​​e kenyang khokahanong ea tlhaiso-leseling e amanang le boemo ba homeostatic le boiphihlelo bo fetileng ka litsamaiso tsa khothatso le moputso. Kakaretso ea data ea anatomical le ea ts'ebetso e hlahisoa ho setšoantšo Figure3.3. Nyutlelie kahare ho LHA, ho kenyelletsa PeF le LHAd, e amohela likhakanyo tse tsoang libakeng tsa boko tse laolang matla le homeostasis ea 'mele ho kenyelletsa libaka tse kenyelletsoeng ho ithuteng ho kopaneng (Broberger et al., 1998; Petrvich et al., 2005; Hurley et al., 2013a). Ka lehlakoreng le leng, libaka tsena tsa LHA li romella likhakanyo ho VTA moo li khothaletsang boitšoaro bo susumetsang, bonyane ka kotloloho ka tokollo ea orexin ho VTA (Phillipson, 1979; Fadel le Deutch, 2002; Geisler le Zahm, 2005). Leha e le setšoantšo Figure33 e bontša sebopeho sa boemo bo phahameng ba ts'ebetso ea LHA e laoloang ke likhokahanyo tse sebetsang hantle ho libaka tse tlase tsa bokong, ho kanna ha etsahala hore potoloho ena ke netweke ea neural e nang le liphetho tsa phihlello lipakeng tsa libaka tse amehang ho ithuteng, homeostasis, le tšusumetso le moputso. Mabapi le sena, ts'ebeliso ea ente ea anterograde le retrograde tracer co-inject e tla fana ka ts'ebeliso ho khetholla hore na libaka tsena li theha marangrang a marang-rang (ka mohlala, Thompson le Swanson, 2010).

Setšoantšo sa 3 

Kakaretso ea merero ea liteko tse lekiloeng. Libaka tse amehang ho ithuteng ho kopaneng (botala) le ho boloka projeke ea homeostasis (e putsoa) ho LHA. LHA e romela likhakanyo libakeng tsa khothatso le moputso (tse khubelu) ho qala boitšoaro bo susumetsang. The ...

Kaha orexin ha e kenelle feela tšebelisanong le boits'oaro bo le bong feela bo susumetsoang, ho ka etsahala hore orexin e nke bohato ba ho matlafatsa likarabo tse lebisitsoeng ho sepheo tse amanang le linaha tse 'maloa tse susumetsoang (Borgland et al., 2009). Lits'oants'o tse amanang le tlhahiso ea moputso le tšebeliso li ka baka ts'ebetso ea li-neuron tsa orexin (Harris et al., 2005; Di Sebastiano et al., 2011; Petrvich et al., 2012), e fana ka tlhahiso ea hore boiphihlelo bo fetileng bo susumetsa tšebetso ea orexin neuron. Ka hona, ho na le bonyane maemo a mabeli a khothalletsang ts'ebetso ea orexin neuron: (1) ho batla le ho sebelisa meputso ka tsela ea 'nete; hape (2) o ithutile ho tloaelana le moputso. Mabapi le ntlha ea bobeli ho bohlokoa ho supa hore orexin e ka kenya polasetiki ea neural ho VTA ka boeona (Borgland et al., 2006). Ha ho na monyetla oa hore orexin e shebane le litlamorao ho boits'oaro bo khothalletsoang bo bonoang ka ho qhekelloa ha LHA, joalo ka ha lipakanyo tse ngata ho tloha ho hypothalamus ho ea VTA ha li sa orexinergic.

Mosebetsi oa nako e tlang o ikemiselitseng ho fuputsa ka hloko karolo ea li-nuclei tse ka har'a LHA o tla hlahisa litholoana. LHA ha e le hantle e na le pokello ea libaka tsa bongoana tse nang le khokahano e ikhethang ea li-neuroanatomical le cytoarchitecture (Swanson et al., 2005; Hahn le Swanson, 2010). Ho feta moo, ho bonahala eka lihlopha tse arohaneng tsa "orexin neuron" li kenngoe tlas'a maemo a fapaneng a liteko (Harris et al., 2005; Harris le Aston-Jones, 2006; Petrvich et al., 2012). Manolo a optogenetic a fana ka mokhoa oa ho lekola hore na li-cluster tsena tsa cell orexin li na le projeke ea bohlokoa ho li-VTA kapa li-nucleus accumbens. Ntle le moo, ho se sebetse ha lihlopha tsa lisele tsa orexin ho lokela ho susumetsa ts'ebetso ea VTA le li-neuron tsa bokellane. Kamora nako, ho bohlokoa ho hlokomela hore liteko tse ngata tse builoeng ha lia ka tsa ikarola le ho hlalosa likarolo tsa methapo ea kelello kahare ho LHA ​​mme ha lia ka tsa bua ka karolo ea DMH ka boits'oaro bo susumetsang. DMH e boetse e fumana likhakanyo tse tsoang libakeng tse nang le metsi homeostasis (Swanson le Lind, 1986), e romela likhakanyo ho VTA (Geisler le Zahm, 2005), hape e na le li-neurons tsa Orexin (Fadel le Deutch, 2002), tseo kaofela li amehang ka boits'oaro bo botle ba lapeng.

Litlamorao tsa bophelo bo botle

Ho ea ka pono ea boits'oaro, mathata a mang a ka nkuoa e le mathata a ho ja. Ka mohlala, li-anorexics li sitoa ho ja lijo tse lekaneng ha ba nang le bothata ba ho nona ba ja lijo tse ngata haholo. Ka mokhoa o ts'oanang, batho ba bang ba ja sodium e ngata haholo; ketsahalo eo ka linako tse ling e bitsoang letsoalo la letsoai (Schulkin, 1986), ha ba bang ba ja sodium e nyane haholo mme ka lebaka leo ba haelloa ke sodium e ba etsa hore ba be le khatello ea maikutlo le pelo le methapo (Bou-Holaigah et al., 1995). Ho feta moo, batho ba baholo ba kanna ba bonts'a lenyora le ho omella ka mor'a moo (Roll le Phillips, 1990; Warren et al., 1994). Mokhoa o mong oa ho utloisisa mafu ana a tšoailoeng ke ntho e fetelletseng kapa e sa sebetseng hantle ka hare ho boits'oaro ke ho e nka e le mathata a ts'ebetso ea methapo e sebetsang e amanang le ho boloka homeostasis le ho etsa ka nepo boitšoaro bo susumetsoang. Ha LHA e kenya letsoho ka mokhoa o hlakileng ho bolokeng homeostasis le boits'ebetsong bo susumetsang, kutlwisiso e ntlafalitsoeng ea LHA e ka thusa ho fumana le ho phekola mafu a ho kenella.

Khohlano ea polelo ea thahasello

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

lumela hore baa fokola

Bangoli ba leboha Young In Kim ka thuso ea hae ea tekheniki le Marilyn Dennis bakeng sa maikutlo a hae. Patlisiso ena e ne e tšehelitsoe ke National Institutes of Health Grants HL14388, HL098207, le MH08241. Bangoli ha ba na liphatlalatso tse tlaleha.

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