Inligting

Kan neurone met elektriese stroom geïnhibeer word?

Kan neurone met elektriese stroom geïnhibeer word?


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

Dit is welbekend dat elektrisiteit gebruik kan word om neurone af te vuur. Maar kan dit gebruik word om neuronale afvuur te inhibeer? Dit is in die konteks van ekstrasellulêre stimulasie. By ekstrasellulêre stimulasie is dit bekend dat daar 'n drempel vir stimulasie en 'n drempel vir skade (elektroporasie) is. Is daar 'n drempel tussen hierdie twee wat neuronvuur sonder enige skade inhibeer? Verskaf asseblief verwysing vir jou antwoord.


Ja, maar miskien nie hoe jy dink nie.

Dit is belangrik om te erken dat spannings verwys na potensiaal verskille. Wanneer ons sê die "'n sel is by -65mV" byvoorbeeld, bedoel ons "Die potensiaalverskil oor die sel se membraan na die ekstrasellulêre ruimte is -65mV." Wanneer jy elektries stimuleer, skep jy 'n verbygaande elektriese veld, waardeur die ekstrasellulêre ruimte nie meer effektief isopotensiaal is nie.

Kom ons verbeel ons ter wille van een of ander neuron dat hierdie veldsterkte in die orde van 40 mV oor die membraan is. As hierdie elektriese veld loodreg op een of ander neuronale proses is, sal die spanning oor die membraan ongeveer -105mV aan die een kant en -25mV aan die ander kant wees. Die -25mV-kant is nou genoeg gedepolariseer om spanningsgehekte natriumkanale oop te maak, en 'n mate van stroom vloei die sel binne. Sodra die skok verby is, sal positiewe stroom deur daardie oop kanale bly vloei en meer kanale oopmaak. Dit maak nie veel saak dat die ander kant kortstondig op -105mV is nie, al wat saak maak, is dat jy 'n klomp spanning-omheinde natriumkanale oopgemaak het wat 'n positiewe terugvoerlus begin.

Daarom sal verbygaande elektriese simulasie byna altyd opwindend wees. Daar is twee uitsonderings:

1) Neurochemiese inhibisie. As jy 'n spesifieke breinstreek opwek wat spesifiek deur inhiberende projeksieneurone bewoon word, sal jy primêr daardie inhiberende selle opwek en dus opwekking elders veroorsaak. Natuurlik, in hierdie geval is die elektriese stimulasie self steeds direk opwindende selle, hulle het toevallig inhiberende effekte elders.

2) Depolarisasieblok. As jy voortdurend dieselfde populasie neurone stimuleer met 'n hoëfrekwensiestimulasie, kan jy neurone in 'n toestand genaamd "depolarisasieblok" plaas. Spanningsbeheerde natriumkanale het 'n kans om te deaktiveer wanneer hulle geaktiveer word. As jy genoeg kanale deaktiveer, is daar nie genoeg beskikbaar om 'n aksiepotensiaal te produseer nie. Daarom, as jy 'n sel feitlik konstant gedepolariseer kan hou deur voortdurend te stimuleer, kan jy aksiepotensiaal-voortplanting voorkom omdat te veel van die spanning-omheinde kanale in die akson-aanvanklike segment geïnaktiveer is.


In die praktyk kan fokale elektriese stimulasie van die brein gebruik word om aanvalle te voorkom of te stop. Daar is 'n toestel hiervoor bemark.

van https://www.scientificamerican.com/article/implant-epilepsy-seizure/

NeuroPace se Responsive Neurostimulation System (RNS), 'n elektriese-stimulasie-inplantaat met twee leidings, wat elk vier elektrodes bevat, wat in die brein geplaas word by die beslagleggingsfokus. Die RNS bespeur elektriese aktiwiteit wat die begin van 'n beslaglegging aandui en lewer direkte elektriese stimulasie om die aktiwiteit te onderbreek en die area te normaliseer.

Dit is nie dadelik vir my duidelik hoekom dit sou werk nie. Die gekoppelde resensie beskryf hoe dit die eerste keer empiries waargeneem is. My verstaan ​​is dat die elektriese stimulasie polarisasie veroorsaak sodanig dat die senuwee nie dadelik weer kan vuur as deel van die epileptiese fokus nie. Soort van 'n teenbrand as jy 'n veldbrand bestry.

Sun FT et al. Responsiewe kortikale stimulasie vir die behandeling van epilepsie.Neuroterapeutika. 2008 Jan;5(1):68-74.

In die 1990's het Durand en kollegas sukses getoon in die onderdrukking van spontane interiktale uitbarstings in vitro deur responsiewe stimulasie direk in die epileptogeniese streek te verskaf. Hul resultaat het voorgestel dat die meganisme vir onderdrukking 'n inhiberende polarisasie is wat veroorsaak word deur die transmembraanstrome wat deur die toegepaste puls gegenereer word. Hierdie proewe in diere het die grondslag gelê vir responsiewe stimulasieterapie vir epilepsie.


Kort antwoord

Ja.

Lang antwoord

Neuronaktiwiteit kan inderdaad geïnhibeer word met die korrekte tipe elektriese insetstimulus.

Trouens, jy kan self rondspeel met verskeie elektriese seinstimuli, en die resultate waarneem nie net vir 'n enkele neuron nie, maar die hele netwerk, self:

https://www.neuron.yale.edu/neuron/

Die skakel hierbo is 'n simulasie-omgewing wat probeer het om neuronale aktiwiteit na te boots gebaseer op gebruikergedefinieerde seinstimuli. Nie net kan jy seine inhibeer nie, maar jy kan makroskopiese gedrag heeltemal beheer: bv. opwekking van hele streke van 'n prototipiese neuronale baan.


Opwekking en inhibisie: Die Yin en Yang van die brein

Om 'n werkende senuweestelsel te maak, is slegs twee kragte nodig: opwekking en inhibisie. Opwindende seine van een sel na die volgende maak die laasgenoemde sel meer geneig om te vuur. Inhiberende sein maak laasgenoemde sel minder geneig om te vuur. By chemiese sinapse in die brein is glutamaat en GABA (gamma-aminobottersuur) oordragstowwe vir onderskeidelik opwekking en inhibisie. Hulle name roep weliswaar nie heeltemal simmetrie op nie - die een verwys na goedkoop kosgeurmiddels en die ander van 'n Sweedse popgroep. Tog is glutamaat en GABA die Yin en Yang van die brein. Dopamien, serotonien, norepinefrien en ander meer gevierde breinchemikalieë het hul bekendheid verwerf as oordragers met baie meer gespesialiseerde effekte. Maar die brood en botter van die brein is ongetwyfeld glutamaat en GABA. In beginsel is 'n senuweestelsel van slegs 'n handjievol neurone en twee oordragstowwe—opwindend en inhiberend— moontlik.

Die balans tussen neurale opwekking en neurale inhibisie is deurslaggewend vir gesonde kognisie en gedrag. 'n Brein wat deur glutamaat oorheers word, sal homself net in herhaalde uitbarstings van aktiwiteit kan opwind, soortgelyk aan 'n epileptiese aanval. Omgekeerd, 'n brein wat deur GABA oorheers word, sal slegs in staat wees tot stille fluisteringe van aktiwiteit, met min sinchronisasie wat nodig is vir betekenisvolle kommunikasie tussen breinareas. Gesonde breinaktiwiteit floreer in die middelarea tussen hierdie twee uiterstes, waar 'n balans tussen opwinding en inhibisie komplekse aktiwiteitspatrone genereer. Dus, 'n skynbaar eenvoudige senuweestelsel wat met slegs glutamaat en GABA gevorm word, lei nietemin tot hoogs komplekse aktiwiteit.

Net so kan 'n oënskynlik eenvoudige mengsel van chemikalieë in 'n petrischaal aanleiding gee tot hoogs komplekse chemiese reaksiepatrone, soos ossillerende spiraalgolwe, wanneer 'n chemikalie wat die reaksie opwek en 'n chemikalie wat die reaksie inhibeer albei teenwoordig is. Hierdie algemene tipe reaksie, wat die Belousov-Zhabotinsky-reaksie genoem word, is selfs bestudeer as 'n model vir hoe neurale netwerke inligting verwerk, aangesien die reaksie se kompleksiteit deur soortgelyke beginsels beheer word.

Omdat daar gedink word dat komplekse patrone van breinaktiwiteit onderliggend is aan buigsame gedrag en kognisie, word die verhouding tussen opwekking en inhibisie - waarna verwys word as E/I-balans - toenemend erken as 'n deurslaggewende maatstaf vir die beoordeling van die fiksheid van enige brein. Skisofrenie, byvoorbeeld, is geassosieer met 'n lae E/I-verhouding wat veroorsaak word deur swak aktiewe glutamaatreseptore. Outisme, aan die ander kant, is geassosieer met 'n hoë E/I-verhouding wat veroorsaak word deur swak aktiewe GABA-reseptore. Selfs groter oormaat opwekking of inhibisie kan onderskeidelik epileptiese aanvalle of breinkoma tot gevolg hê. Trouens, individue met outisme is baie meer geneig om epilepsie te hê - 'n toestand wat aanvalle veroorsaak - as die gemiddelde persoon, wat daarop dui dat beide outisme en epilepsie in 'n hoë E/I-verhouding gewortel is.

Hoe werk die sinergie tussen opwekking en inhibisie? Beide opwinding en inhibisie, wat alleen optree, lok die brein na duidelike patrone van relatief eenvoudige aktiwiteit. Die balans van beide skep 'n kritieke toestand, soos die grens tussen 'n gas en 'n vloeistof. Buite die brein is baie kritieke toestande onstabiel, soos 'n potlood wat vertikaal op sy punt gebalanseer is, maar omval na enige verdere verandering in sy posisie. Tog is dit verbasend dat kritieke toestande in die brein dikwels selfonderhou en sterk is vir verdere veranderinge. Byvoorbeeld, nadat sinaptiese insette na 'n neurale netwerk 'n kritieke toestand gegenereer het, handhaaf verdere sinaptiese insette die kritieke toestand eerder as om die netwerk in 'n eenvoudige, stabiele patroon te druk. Om hierdie rede word die verskynsel self-georganiseerde kritiekheid, of SOC genoem, 'n term vir die konsep wat ontwikkel is deur fisici Per Bak, Chao Tang en Kurt Wiesenfeld van die Brookhaven National Laboratory in New York.

SOC word beskou as belangrik vir breinfunksie omdat dit die brein 'n sekere mate van buigsaamheid toelaat. Net soos 'n kritieke stof buigsaam kan wissel tussen 'n gas- en 'n vloeibare toestand, kan SOC die brein toelaat om baie verskillende aktiwiteitstoestande te besoek. Waar SOC ook al in die natuur waargeneem word, blyk dit komplekse aktiwiteit oor baie tydelike en ruimtelike skale te produseer as gevolg van 'n stadige proses wat energie bou en 'n vinnige proses wat energie versprei. Hierdie kompleksiteit kan beskryf word deur 'n patroon wat 'n skaalvrye verspreiding genoem word. Anders as die normale verspreiding of "klokkurwe" wat ons uit die statistiekklas ken, het 'n skaalvrye verspreiding geen gemiddelde of gemiddelde nie.

Om SOC beter te verstaan, het Bak en sy kollegas 'n bekende scenario voorgestel: die bou van 'n sandhoop by die strand. Die sandhoop word groter totdat sy helling 'n sekere steilte bereik wat 'n kritieke toestand tot gevolg het. Deur meer sand by te voeg, veroorsaak dit sneeustortings van verskillende groottes. Trouens, die kritieke toestand duur voort selfs as jy meer sand byvoeg—dit is werklik self-georganiseerd.

Die twee kompeterende prosesse in hierdie voorbeeld is die stadige proses om sand by te voeg, wat energie bou, en die vinnige proses wat voortspruit uit die swaartekrag wat die kragwrywing oorkom, wat energie versprei. Miskien voel hierdie voorbeeld ver verwyderd van die brein. Maar die stadige proses om sand by te voeg, is eintlik analoog aan die toevoeging van opwindende sinaptiese insette in 'n neurale netwerk. Net so is die vinnige proses van swaartekrag wat wrywing oorkom, analoog aan neurale opwekking wat neurale inhibisie oorkom en uitbarstings van vuur veroorsaak—neuronale sneeustortings. Sandhoop sneeustortings volg dieselfde skaalvrye verspreiding wat in elektriese breinopnames waargeneem word: Aktiwiteit word op alle skale en frekwensies waargeneem, 'n gevolg van delikate E/I-balans.

Trouens, ons kan die sandhoopmodel verander om siektetoestande te simuleer waar opwekking en inhibisie ongebalanseerd is. Stel jou voor dat jy 'n hoop bou van glaskrale eerder as sandkorrels. Die gladde krale plak nie goed nie, en die brose hoop stort ineen soos 'n Jenga-toring sodra dit 'n kritieke massa bereik, en bereik nooit ware self-georganiseerde kritiek nie. Dit is analoog aan toestand van oormatige neurale opwekking: sinaptiese inhibisie is te swak om die storms van opwindende bars te stop wat komplekse seine onderbreek en aanvalle vorm. Omgekeerd, stel jou voor dat jy 'n sandhoop bou met nat sand. Die nat sand is taai, wat min sneeustortings tot gevolg het aangesien die samehorigheid van die sand te hoog is. Dit is analoog aan 'n toestand van oormatige neurale inhibisie: Opwindende dryfkrag kan nie die verstikkende greep van sinaptiese inhibisie oorkom nie, wat neurale berekeninge wat van komplekse seinering afhanklik is, belemmer.

Omdat elektriese breinaktiwiteit maklik waargeneem kan word deur elektrodes op die kopvel (EEG) te plaas, is dit moontlik vir navorsers en klinici om E/I-balans af te lei sonder om selle in die brein direk te ondersoek. Byvoorbeeld, epileptiforme ontladings - uitbarstings van ontwrigtende opgewondenheid - is duidelike tekens van 'n hoë E/I-verhouding. Hierdie ontladings kan aandui dat die brein verby kritiek gedryf is na a superkrities staat. Alhoewel dit tradisioneel met epilepsie geassosieer word, kan epileptiforme afskeidings ook voorkom in die EEG's van pasiënte wat nog nooit 'n enkele aanval gehad het nie. 'n Ontluikende konsep van epilepsiespektrumafwykings poog om geestesiektes, soos paniekversteuring, in dieselfde konteks as epilepsie te raam. Dr. Nash N. Boutros aan die Universiteit van Missouri, Kansas City ondersoek epileptiforme afskeidings by pasiënte met paniekaanvalle as moontlike aanwysers van dieselfde hoë E/I-verhouding wat epilepsie veroorsaak. As paniekversteurings en epilepsie 'n algemene oorsaak het, kan hulle albei met anti-epileptiese middels behandel word. Terwyl sulke middels oor die algemeen aanvalle behandel, word geglo dat dit neuronale prikkelbaarheid verminder en is ook deur die FDA goedgekeur om bipolêre versteuring te behandel, 'n psigiatriese versteuring waar pasiënte toestande van beide verhoogde en verlaagde bui ervaar.

In die nabye toekoms kan middels wat neuronale prikkelbaarheid verander, belofte toon om die siek brein na E/I-balans te lei. Inderdaad, net soos baie geestelike praktyke die handhawing van 'n "innerlike balans" voorstaan, blyk 'n fisiese balans tussen opponerende kragte sentraal te wees om 'n gesonde brein te handhaaf. Die sinergie tussen teenoorgesteldes wat in die brein waargeneem word, herinner ons daaraan dat kompleksiteit 'n balans vereis. Terwyl empiriese bewyse getoon het dat breingrootte of breinmassa nie die beste maatstaf van breinfiksheid is nie, kan E/I-balans eerder vir daardie titel veg. Eendag kan 'n ondersoek by die dokter se kantoor nie net die neem van jou pols, lengte en gewig behels nie, maar ook 'n EEG-lesing van jou E/I-verhouding.

Gruenert, Gerd, Peter Dittrich, en Klaus-Peter Zauner. "Kunsmatige nat neuronale netwerke van kompartementaliseerde opgewonde chemiese media." ERCIM NUUS 85 (2011): 30-32.

Vanag, Vladimir K., en Irving R. Epstein. "Opwindende en inhiberende koppeling in 'n eendimensionele reeks Belousov-Zhabotinsky mikro-ossillators: Teorie." Fisiese Oorsig E 84.6 (2011): 066209.

Buzsaki, Gyorgy. Ritmes van die brein. Oxford University Press, 2006.

Bak, Per. "Hoe die natuur werk: die wetenskap van self-georganiseerde kritiek." Nature 383.6603 (1996): 772-773.

Tetzlaff, Christian, et al. "Self-georganiseerde kritiek in die ontwikkeling van neuronale netwerke." PLoS Comput Biol 6.12 (2010): e1001013.

Boutros, Nash N., et al. "Epilepsiespektrumafwykings: 'n konsep wat bekragtiging of weerlegging benodig." Mediese hipoteses 85.5 (2015): 656-663.

Boutros, Nash N., et al. "Voorspellende waarde van geïsoleerde epileptiforme ontladings vir 'n gunstige terapeutiese reaksie op anti-epileptiese middels in nie-epileptiese psigiatriese pasiënte." Tydskrif vir Kliniese Neurofisiologie 31.1 (2014): 21-30.


Glukose-sensitiewe neurone van die hipotalamus

Gespesialiseerde subgroepe van hipotalamiese neurone vertoon spesifieke opwindende of inhiberende elektriese reaksies op veranderinge in ekstrasellulêre vlakke van glukose. Daar is tradisioneel aanvaar dat glukose-opgewekte neurone 'n 'beta-sel' glukose-waarnemingstrategie gebruik, waar glukose sitosoliese ATP verhoog, wat KATP-kanale sluit wat Kir6.2-subeenhede bevat, wat depolarisasie en verhoogde prikkelbaarheid veroorsaak. Onlangse bevindinge dui daarop dat alhoewel elemente van hierdie kanoniese model funksioneel is in sommige hipotalamus-selle, hierdie pad nie universeel noodsaaklik is vir die opwekking van glukose-sensitiewe neurone deur glukose nie. Dus is glukose-geïnduseerde opwekking van boogvormige kernneurone onlangs gerapporteer in muise wat Kir6.2 ontbreek, en geen beduidende toenames in sitosoliese ATP-vlakke kon in hipotalamus-neurone na veranderinge in ekstrasellulêre glukose opgespoor word nie. Moontlike alternatiewe glukose-waarnemingstrategieë sluit in elektrogeniese glukosetoetreding, glukose-geïnduseerde vrystelling van gliale laktaat en ekstrasellulêre glukosereseptore. Glukose-geïnduseerde elektriese inhibisie word baie minder verstaan ​​as opwekking, en is voorgestel om vermindering in die depolariserende aktiwiteit van die Na+/K+ pomp te behels, of aktivering van 'n hiperpolariserende Cl-stroom. Ondersoeke van neurotransmitter-identiteite van glukose-sensitiewe neurone begin gedetailleerde inligting verskaf oor hul fisiologiese rolle. In die muis laterale hipotalamus word oreksien/hipokretienneurone (wat wakkerheid, bewegingsaktiwiteit en vreetsoek bevorder) glukose-geïnhibeer, terwyl melanien-konsentrerende hormoonneurone (wat slaap en energiebesparing bevorder) glukose-opgewonde is. In die hipotalamus-boogkern is opwindende aksies van glukose op anoreksigeniese POMC-neurone in muise gerapporteer, terwyl die eetlus-bevorderende NPY-neurone direk deur glukose geïnhibeer kan word. Hierdie resultate beklemtoon die fundamentele belangrikheid van hipotalamus-glukose-waarnemende neurone in die orkestrering van slaap-wakker-siklusse, energieverbruik en voedingsgedrag.

Syfers

Model vir hoe aksies van glukose op neurone van die laterale hipotalamus...

Veelvuldige paaie sal waarskynlik ...

Veelvuldige paaie sal waarskynlik betrokke wees by die modulasie van die elektriese ...


Opinie: Die oorgesiene krag van inhiberende neurone

Lauren Aguirre
1 Junie 2021

BO: GEWYSIG VANAF © ISTOCK.COM, EERSTE SIGNAL

W anneer ons dink oor hoe die brein werk—of hoe om dit reg te maak—is ons geneig om aan neuro-oordragstowwe soos serotonien of dopamien te dink. Maar die brein is 'n elektriese orgaan, sy geldeenheid is die impulse wat oor duisende kilometers van neurone vlieg. Soos ek in my nuwe boek beskryf, Die geheuedief en die geheime agter hoe ons onthou: 'n mediese raaisel, meer elektriese aktiwiteit is nie altyd beter nie. Trouens, hiperaktiwiteit in die hippokampus - die brein se geheuesentrum - is 'n vroeë teken van Alzheimer se siekte wat agterstallige belangstelling as 'n terapeutiese teiken kry.

Neurone kom in twee hoof "geure," opwindend en inhiberend. Wanneer 'n opwindende neuron genoeg insette van ander opwindende neurone ontvang, skiet dit, en stuur daardie sein langs sy akson na vennote stroomaf. Inhiberende neurone vertel gewoonlik ander neurone nie om te vuur. Hulle is minder volop as opwindende neurone, maar meer divers. Op sommige maniere is hulle die werklike breine van die stelsel, die masjiene in die agtergrond wat 'n onophoudelike gebrom van elektriese aktiwiteit pas en koördineer.

Die bes bestudeerde inhiberende neuron word 'n mandjiesel genoem, so genoem omdat sy akson in baie filamente verdeel en soos 'n mandjie om die selliggaam van ander neurone draai, die punt waar dit maksimum beheer kan uitoefen. Mandselle het 'n relatief eenvoudige taak: hulle tree op as hekwagters, wat opwindende neurone toelaat om te vuur of te verhoed dat hulle dit doen. ’n Enkele mandjiesel kan die uitset van honderde of selfs duisende opwindende neurone beheer en sinchroniseer, hulle aan- en afskakel met presiese tydsberekening en ’n ritmiese toutrekkery opstel wat breingolwe skep. Breingolwe laat op hul beurt toe dat inligting gekoördineer en oor lang afstande oorgedra word. Wanneer inhiberende neurone ophou om goed te werk, verval hierdie delikate balans tussen opwekking en inhibisie, en breingolwe word minder koherent.

Toe navorsers hippokampale hiperaktiwiteit die eerste keer as 'n vroeë Alzheimer-simptoom geïdentifiseer het, het hulle aanvaar dat dit kompenserend was, 'n manier om die volume op swak kommunikasie tussen neurone te verhoog. Navorsers verstaan ​​nou dat hierdie verlies aan inhibisie soos agtergrondstatika is wat inmeng met geheueherwinning, en leidrade dui op inhiberende neurone as noodsaaklike spelers in die ketting van gebeure wat plaasvind soos Alzheimer se vorder. Byvoorbeeld, selfs kognitief normale ouer volwassenes het hiperaktiwiteit in die hippokampus en akkumulasie van tau-proteïen daarmee saam. Benewens taai amyloïed beta-plate, is hierdie giftige tau-proteïene 'n bepalende kenmerk van die siekte. Nog 'n leidraad is dat aanvalle, wat voorkom wanneer opwindende neurone onbeheerbaar vuur, meer algemeen voorkom by mense met Alzheimers as daarsonder, word vermoed dat dit die vordering daarvan versnel, en kan in die vroeë stadiums verskyn - miskien selfs voor ander tekens van siekte. ’n Derde leidraad is dat een tipe breingolf, genaamd gamma, swakker is by mense met Alzheimers. Hierdie insigte dui daarop dat die aanpassing van die balans tussen opwinding en inhibisie geheue kan verbeter en die siekte se vordering kan vertraag.

Navorsers ondersoek verskeie benaderings om daardie balans te herkalibreer. Die verste langs is 'n Fase 3 kliniese proef van 'n wyd gebruikte middel teen beslaglegging genaamd levetiracetam. Die Amerikaanse maatskappy agter die proef, AgeneBio, toets of 'n verlengde-vrystelling, baie lae dosis agtergrondhiperaktiwiteit genoeg verminder om geheue in die vroegste stadiums van Alzheimer's te verbeter. ’n Tweede aanvalshoek is om die breingolwe wat deur inhiberende neurone gegenereer word, te manipuleer. Navorsers by 'n maatskappy genaamd Cognito Therapeutics, by MIT, en elders is besig met verskeie onafhanklike proewe wat eksterne flikkerende ligte en klank gebruik om gamma-ritmes mee te voer en te versterk. 'n Derde aanpak, wat tans in muise getoets word, is om geneties verbeterde inhiberende neurone in die brein oor te plant.

Daar word ook gedink dat foutiewe elektriese kommunikasie 'n rol speel in ander breinafwykings en -siektes, insluitend epilepsie, skisofrenie, depressie en outisme. Ons begrip van inhiberende neurone is in sy kinderskoene in vergelyking met wat ons van neuro-oordragstowwe weet. Omdat neuro-oordragstowwe verskeie rolle speel en dus baie newe-effekte het, kan hulle optree soos 'n farmakologiese kombers wat oor die hele brein se delikate werking gelê word. Miskien, as navorsers uitvind hoe om die inhiberende neurone wat by elke siekte betrokke is, te teiken, kan hulle meer gesofistikeerde maniere ontwikkel om honderde miljoene mense regoor die wêreld te help wat aan hierdie aftakelende breinsiektes ly.

Lauren Aguirre is 'n wetenskapjoernalis wie se werk in die PBS-reeks verskyn het NOVA, The Atlantic, Undark Magazine, en STAT. Lees 'n uittreksel uit Die geheuedief hier.


Onlangse vordering in die ontdekking van Kv7-modulators

Ismet Dorange, Britt-Marie Swahn, in Jaarverslae in Medisinale Chemie, 2011

3.1 Funksie

Subeenhede Kv7.2 en Kv7.3 kom saam en vorm 'n tetrameer wat onderliggend is aan die M-stroom [19] . Dit is opmerklik dat ander subeenhede (Kv7.4 en Kv7.5) ook geassosieer word, al is dit in 'n mindere mate, met M stroomkenmerke [20,21]. Die M-stroom wat by 'n laer drempel membraanpotensiaal geaktiveer word as wat normaalweg neuronale selle sou aktiveer, hiperpolariseer die selmembraan en verminder gevolglik die afvuur van aksiepotensiaal. Met ander woorde, modulasie van hierdie kanale kan neuronale prikkelbaarheid beheer. Met die erkenning dat neuronale hiperprikkelbaarheid die oorsaak is van verskeie kliniese afwykings soos epilepsie en pyn, verteenwoordig modulasie van hierdie kanale 'n aantreklike benadering vir die behandeling van sulke toestande.


Ontwakende dormante neurone kan siekteveranderende Parkinson’-behandeling verskaf, vroeë studie stel voor

Saam met sterwende senuweeselle kan dormante neurone ook die hoofoorsaak van Parkinson’ se siekte wees, volgens 'n onlangse studie in dieremodelle.

Om hierdie neurone te herontwaak deur 'n tipe breinselle genaamd astrocyte te teiken, kan dopamienproduksie in die brein herstel en Parkinson’ se motoriese simptome omkeer, het die studie bevind. Hierdie bevindinge kan lei tot 'n potensiële nuwe siekte-modifiserende behandeling, veral in die vroeë stadiums van Parkinson’s.

Ten spyte van sy voorkoms en aftakelende gevolge, huidige mediese terapie vir Parkinson’s staatmaak op die verligting van simptome. Navorsing wat maniere ondersoek om die siekte te verander of die simptome daarvan om te keer, is skaars, gebaseer op die vaste oortuiging dat Parkinson’s veroorsaak word deur die onomkeerbare dood van senuweeselle - ook genoem neurone - in 'n gebied van die brein wat die substantia nigra.

In hierdie breinstreek is senuweeselle bekend as dopaminerge neurone verantwoordelik vir die vervaardiging van die neurotransmitter dopamien, 'n chemiese boodskapper wat senuweeselle toelaat om te kommunikeer. Dopamien speel 'n sleutelrol in motoriese funksiebeheer en is ook betrokke by gedrag en kognisie, geheue en leer, slaap en bui.

Levodopa, 'n steunpilaar van Parkinson’s behandeling, werk deur ekstra dopamien aan die brein te verskaf. Dit verlig egter net motoriese simptome en verander nie die siekteverloop nie. Boonop kan die langtermyngebruik daarvan ernstige newe-effekte veroorsaak, insluitend onwillekeurige, wisselvallige en kronkelende bewegings.

Nou het 'n span Koreaanse navorsers bykomende leidrade ontdek oor die onderliggende meganismes van Parkinson’s wat hoop kan bied vir die ontwikkeling van siekte-modifiserende behandelings wat die toestand kan omkeer.

Met behulp van muis- en rotmodelle van Parkinson’s, het hulle gevind dat die motoriese abnormaliteite wat die siekte merk, vroeër begin as wat voorheen gedink is. Hulle word geaktiveer wanneer dopaminerge neurone in die substantia nigra leef nog, maar in 'n dormante toestand, nie in staat om dopamien te produseer nie.

Wat egter die sleutel tot daardie dormante toestand hou, is 'n ander soort selle wat astrocyte genoem word, stervormige selle wat in die brein en rugmurg teenwoordig is wat belangrike rolle speel in die beskerming en regulering van die senuweestelsel.

Wanneer neurone sterf, reageer nabygeleë astrasiete deur te prolifereer, en begin om 'n inhiberende neurotransmitter genaamd gamma-aminobottersuur (GABA) teen oormatige vlakke vry te stel. Dit plaas naburige neurone “on hold,”, wat hul produksie van dopamien opskort.

GABA verhoed dat die neurone elektriese impulse afvuur en veroorsaak dat hulle ophou om 'n ensiem te maak, genaamd tyrosienhidroksilase, wat noodsaaklik is vir die produksie van dopamien. In werklikheid plaas GABA die neurone in 'n dormante of slaaptoestand.

Een van die belangrikste ontdekkings van die studie was dat oorlewende dormante neurone eintlik “ontwaak” uit hul “slaap” toestand en gered kon word om motoriese simptome te verlig.

“Almal is so vasgevang in die konvensionele idee van die neuronale dood as die enkele oorsaak van PD. Dit belemmer pogings om die rolle van ander neuronale aktiwiteite, soos omliggende astrasiete, te ondersoek,” C. Justin Lee, PhD, die studie’ se ooreenstemmende skrywer, het in 'n persverklaring gesê.

“Die neuronale dood het enige moontlikheid om PD om te keer, uitgesluit. Aangesien dormante neurone wakker gemaak kan word om hul produksievermoë te hervat, sal hierdie bevinding ons toelaat om PD-pasiënte hoop te gee om 'n nuwe lewe sonder PD te lei,” het Lee bygevoeg.

Behandeling met twee verskillende verbindings wat GABA-produksie in astrasiete blokkeer, genaamd monoamienoksidase-B, of MAO-B, inhibeerders, was voldoende vir neurone om die ensiematiese masjinerie te herstel wat nodig is om dopamien te produseer, het die studie bevind. Dit het Parkinson’ se motoriese simptome in die studiediere aansienlik verlig.

Trouens, die MAO-B-remmers wat vir die studie gebruik word - selegilien (handelsname Eldepryl, Carbex, Zelapar, onder andere), en safinamide (handelsnaam Xadago) - word reeds aan Parkinson se pasiënte voorgeskryf as 'n bykomende terapie om levodopa. Daar word geglo dat hulle die afbreek van dopamien in die brein voorkom.

Wat belangrik is, is dat die bestaan ​​van dormante neurone in die brein van menslike pasiënte waargeneem is. Ontleding van nadoodse breine van individue met ligte en ernstige Parkinson’s het 'n beduidende bevolking van dormante neurone omring deur talle GABA-produserende astrasiete gehad.

Die navorsers hoop dat “ontwaking” neurone met behulp van MAO-B inhibisie `n effektiewe siekte-modifiserende terapeutiese strategie vir Parkinson’s kan wees, veral vir pasiënte in die vroeë stadiums van die siekte. Op daardie tydstip is onaktiewe, dog lewende dopaminergiese neurone steeds teenwoordig.

Alhoewel die resultate van verskeie kliniese proewe twyfel gebring het oor die terapeutiese doeltreffendheid van tradisionele MAO-B-inhibeerders, sê navorsers dat hulle onlangs 'n nuwe inhibeerder, KDS2010, ontwikkel het. KDS2010 inhibeer effektief astrocytiese GABA-produksie met minimale newe-effekte in Alzheimer se dieremodelle en kan ook effektief wees om Parkinson se motoriese simptome te verlig, het die ondersoekers gesê.

“Hierdie navorsing weerlê die algemene oortuiging dat daar geen siekteveranderende behandeling vir PD is nie as gevolg van die basis daarvan op neuronale seldood,” sê Hoon Ryu, PhD, 'n navorser by KIST Brain Science Institute, in Suid-Korea, en een van die senior skrywers van die studie.

“Die betekenis van hierdie studie lê in sy potensiaal as die nuwe vorm van behandeling vir pasiënte in vroeë stadiums van PD,” gesê Ryu.

Die feit dat inhibisie van dopaminerge neurone deur omliggende astrasiete een van die kernoorsake van Parkinson’s is, behoort 'n “drastiese keerpunt” te wees in die begrip en behandeling van nie net Parkinson’s nie, maar ook ander neurodegeneratiewe siektes, het Sang Ryong Jeon bygevoeg, MD, PhD, ook 'n navorser by KIST en 'n studie mede-outeur.


Skrywer(s)

Knowing Neurons is 'n bekroonde neurowetenskaponderwys- en uitreikwebwerf wat deur jong neurowetenskaplikes geskep is. Die globale spanlede by Knowing Neurons verduidelik ingewikkelde idees oor die brein en verstand duidelik en akkuraat deur kragtige beelde, infografika en animasies te gebruik om geskrewe inhoud te verbeter. Met 'n uitgebreide sosiale media-teenwoordigheid het Knowing Neurons 'n belangrike wetenskapkommunikasie-uitlaat en hulpbron vir beide studente en onderwysers geword.


Inhoud

Neurone is die primêre komponente van die senuweestelsel, saam met die gliale selle wat hulle strukturele en metaboliese ondersteuning gee. Die senuweestelsel bestaan ​​uit die sentrale senuweestelsel, wat die brein en rugmurg insluit, en die perifere senuweestelsel, wat die outonome en somatiese senuweestelsels insluit. By gewerwelde diere behoort die meerderheid neurone aan die sentrale senuweestelsel, maar sommige woon in perifere ganglia, en baie sensoriese neurone is geleë in sensoriese organe soos die retina en koglea.

Aksone kan in binde saambind waaruit die senuwees in die perifere senuweestelsel bestaan ​​(soos drade wat kabels uitmaak). Bundels van aksone in die sentrale senuweestelsel word bane genoem.

Neurone is hoogs gespesialiseerd vir die verwerking en oordrag van sellulêre seine. Gegewe hul diversiteit van funksies wat in verskillende dele van die senuweestelsel uitgevoer word, is daar 'n groot verskeidenheid in hul vorm, grootte en elektrochemiese eienskappe. Byvoorbeeld, die soma van 'n neuron kan wissel van 4 tot 100 mikrometer in deursnee. [1]

  • Die soma is die liggaam van die neuron. Aangesien dit die kern bevat, vind die meeste proteïensintese hier plaas. Die kern kan wissel van 3 tot 18 mikrometer in deursnee. [2]
  • Die dendriete van 'n neuron is sellulêre uitbreidings met baie vertakkings. Hierdie algehele vorm en struktuur word metafories na verwys as 'n dendritiese boom. Dit is waar die meeste insette na die neuron via die dendritiese ruggraat plaasvind.
  • Die akson is 'n fyner, kabelagtige projeksie wat tientalle, honderde of selfs tienduisende keer die deursnee van die soma in lengte kan strek. Die akson dra hoofsaaklik senuwee-seine weg van die soma, en dra sekere soorte inligting terug na dit. Baie neurone het net een akson, maar hierdie akson kan - en sal gewoonlik - uitgebreide vertakking ondergaan, wat kommunikasie met baie teikenselle moontlik maak. Die deel van die akson waar dit uit die soma kom, word die genoem akson heuwel. Besides being an anatomical structure, the axon hillock also has the greatest density of voltage-dependent sodium channels. This makes it the most easily excited part of the neuron and the spike initiation zone for the axon. In electrophysiological terms, it has the most negative threshold potential.
    • While the axon and axon hillock are generally involved in information outflow, this region can also receive input from other neurons.

    The accepted view of the neuron attributes dedicated functions to its various anatomical components however, dendrites and axons often act in ways contrary to their so-called main function. [ aanhaling nodig ]

    Axons and dendrites in the central nervous system are typically only about one micrometer thick, while some in the peripheral nervous system are much thicker. The soma is usually about 10–25 micrometers in diameter and often is not much larger than the cell nucleus it contains. The longest axon of a human motor neuron can be over a meter long, reaching from the base of the spine to the toes.

    Sensory neurons can have axons that run from the toes to the posterior column of the spinal cord, over 1.5 meters in adults. Giraffes have single axons several meters in length running along the entire length of their necks. Much of what is known about axonal function comes from studying the squid giant axon, an ideal experimental preparation because of its relatively immense size (0.5–1 millimeters thick, several centimeters long).

    Fully differentiated neurons are permanently postmitotic [3] however, stem cells present in the adult brain may regenerate functional neurons throughout the life of an organism (see neurogenesis). Astrocytes are star-shaped glial cells. They have been observed to turn into neurons by virtue of their stem cell-like characteristic of pluripotency.

    Membrane Edit

    Like all animal cells, the cell body of every neuron is enclosed by a plasma membrane, a bilayer of lipid molecules with many types of protein structures embedded in it. A lipid bilayer is a powerful electrical insulator, but in neurons, many of the protein structures embedded in the membrane are electrically active. These include ion channels that permit electrically charged ions to flow across the membrane and ion pumps that chemically transport ions from one side of the membrane to the other. Most ion channels are permeable only to specific types of ions. Some ion channels are voltage gated, meaning that they can be switched between open and closed states by altering the voltage difference across the membrane. Others are chemically gated, meaning that they can be switched between open and closed states by interactions with chemicals that diffuse through the extracellular fluid. The ion materials include sodium, potassium, chloride, and calcium. The interactions between ion channels and ion pumps produce a voltage difference across the membrane, typically a bit less than 1/10 of a volt at baseline. This voltage has two functions: first, it provides a power source for an assortment of voltage-dependent protein machinery that is embedded in the membrane second, it provides a basis for electrical signal transmission between different parts of the membrane.

    Histology and internal structure Edit

    Numerous microscopic clumps called Nissl bodies (or Nissl substance) are seen when nerve cell bodies are stained with a basophilic ("base-loving") dye. These structures consist of rough endoplasmic reticulum and associated ribosomal RNA. Named after German psychiatrist and neuropathologist Franz Nissl (1860–1919), they are involved in protein synthesis and their prominence can be explained by the fact that nerve cells are very metabolically active. Basophilic dyes such as aniline or (weakly) haematoxylin [4] highlight negatively charged components, and so bind to the phosphate backbone of the ribosomal RNA.

    The cell body of a neuron is supported by a complex mesh of structural proteins called neurofilaments, which together with neurotubules (neuronal microtubules) are assembled into larger neurofibrils. [5] Some neurons also contain pigment granules, such as neuromelanin (a brownish-black pigment that is byproduct of synthesis of catecholamines), and lipofuscin (a yellowish-brown pigment), both of which accumulate with age. [6] [7] [8] Other structural proteins that are important for neuronal function are actin and the tubulin of microtubules. Class III β-tubulin is found almost exclusively in neurons. Actin is predominately found at the tips of axons and dendrites during neuronal development. There the actin dynamics can be modulated via an interplay with microtubule. [9]

    There are different internal structural characteristics between axons and dendrites. Typical axons almost never contain ribosomes, except some in the initial segment. Dendrites contain granular endoplasmic reticulum or ribosomes, in diminishing amounts as the distance from the cell body increases.

    Neurons vary in shape and size and can be classified by their morphology and function. [11] The anatomist Camillo Golgi grouped neurons into two types type I with long axons used to move signals over long distances and type II with short axons, which can often be confused with dendrites. Type I cells can be further classified by the location of the soma. The basic morphology of type I neurons, represented by spinal motor neurons, consists of a cell body called the soma and a long thin axon covered by a myelin sheath. The dendritic tree wraps around the cell body and receives signals from other neurons. The end of the axon has branching axon terminals that release neurotransmitters into a gap called the synaptic cleft between the terminals and the dendrites of the next neuron.

    Structural classification Edit

    Polarity Edit

    Most neurons can be anatomically characterized as:

      : single process : 1 axon and 1 dendrite : 1 axon and 2 or more dendrites
        : neurons with long-projecting axonal processes examples are pyramidal cells, Purkinje cells, and anterior horn cells : neurons whose axonal process projects locally the best example is the granule cell

      Ander wysig

      Some unique neuronal types can be identified according to their location in the nervous system and distinct shape. Enkele voorbeelde is:

        , interneurons that form a dense plexus of terminals around the soma of target cells, found in the cortex and cerebellum , large motor neurons , interneurons of the cerebellum , most neurons in the corpus striatum , huge neurons in the cerebellum, a type of Golgi I multipolar neuron , neurons with triangular soma, a type of Golgi I , neurons with both ends linked to alpha motor neurons , interneurons with unique dendrite ending in a brush-like tuft , a type of Golgi II neuron cells, motoneurons located in the spinal cord , interneurons that connect widely separated areas of the brain

      Functional classification Edit

      Direction Edit

        convey information from tissues and organs into the central nervous system and are also called sensory neurons. (motor neurons) transmit signals from the central nervous system to the effector cells. connect neurons within specific regions of the central nervous system.

      Afferent and efferent also refer generally to neurons that, respectively, bring information to or send information from the brain.

      Action on other neurons Edit

      A neuron affects other neurons by releasing a neurotransmitter that binds to chemical receptors. The effect upon the postsynaptic neuron is determined by the type of receptor that is activated, not by the presynaptic neuron or by the neurotransmitter. A neurotransmitter can be thought of as a key, and a receptor as a lock: the same neurotransmitter can activate multiple types of receptors. Receptors can be classified broadly as excitatory (causing an increase in firing rate), inhibitory (causing a decrease in firing rate), or modulatory (causing long-lasting effects not directly related to firing rate).

      The two most common (90%+) neurotransmitters in the brain, glutamate and GABA, have largely consistent actions. Glutamate acts on several types of receptors, and has effects that are excitatory at ionotropic receptors and a modulatory effect at metabotropic receptors. Similarly, GABA acts on several types of receptors, but all of them have inhibitory effects (in adult animals, at least). Because of this consistency, it is common for neuroscientists to refer to cells that release glutamate as "excitatory neurons", and cells that release GABA as "inhibitory neurons". Some other types of neurons have consistent effects, for example, "excitatory" motor neurons in the spinal cord that release acetylcholine, and "inhibitory" spinal neurons that release glycine.

      The distinction between excitatory and inhibitory neurotransmitters is not absolute. Rather, it depends on the class of chemical receptors present on the postsynaptic neuron. In principle, a single neuron, releasing a single neurotransmitter, can have excitatory effects on some targets, inhibitory effects on others, and modulatory effects on others still. For example, photoreceptor cells in the retina constantly release the neurotransmitter glutamate in the absence of light. So-called OFF bipolar cells are, like most neurons, excited by the released glutamate. However, neighboring target neurons called ON bipolar cells are instead inhibited by glutamate, because they lack typical ionotropic glutamate receptors and instead express a class of inhibitory metabotropic glutamate receptors. [12] When light is present, the photoreceptors cease releasing glutamate, which relieves the ON bipolar cells from inhibition, activating them this simultaneously removes the excitation from the OFF bipolar cells, silencing them.

      It is possible to identify the type of inhibitory effect a presynaptic neuron will have on a postsynaptic neuron, based on the proteins the presynaptic neuron expresses. Parvalbumin-expressing neurons typically dampen the output signal of the postsynaptic neuron in the visual cortex, whereas somatostatin-expressing neurons typically block dendritic inputs to the postsynaptic neuron. [13]

      Discharge patterns Edit

      Neurons have intrinsic electroresponsive properties like intrinsic transmembrane voltage oscillatory patterns. [14] So neurons can be classified according to their electrophysiological characteristics:

      • Tonic or regular spiking. Some neurons are typically constantly (tonically) active, typically firing at a constant frequency. Example: interneurons in neurostriatum.
      • Phasic or bursting. Neurons that fire in bursts are called phasic.
      • Fast spiking. Some neurons are notable for their high firing rates, for example some types of cortical inhibitory interneurons, cells in globus pallidus, retinal ganglion cells. [15][16]

      Neurotransmitter Edit

      • Cholinergic neurons—acetylcholine. Acetylcholine is released from presynaptic neurons into the synaptic cleft. It acts as a ligand for both ligand-gated ion channels and metabotropic (GPCRs) muscarinic receptors. Nicotinic receptors are pentameric ligand-gated ion channels composed of alpha and beta subunits that bind nicotine. Ligand binding opens the channel causing influx of Na + depolarization and increases the probability of presynaptic neurotransmitter release. Acetylcholine is synthesized from choline and acetyl coenzyme A.
      • Adrenergic neurons—noradrenaline. Noradrenaline (norepinephrine) is release from most postganglionic neurons in the sympathetic nervous system onto two sets of GPCRs: alpha adrenoceptors and beta adrenoceptors. Noradrenaline is one of the three common catecholamine neurotransmitter, and the most prevalent of them in the peripheral nervous system as with other catecholamines, it is synthesised from tyrosine.
      • GABAergic neurons—gamma aminobutyric acid. GABA is one of two neuroinhibitors in the central nervous system (CNS), along with glycine. GABA has a homologous function to ACh, gating anion channels that allow Cl − ions to enter the post synaptic neuron. Cl − causes hyperpolarization within the neuron, decreasing the probability of an action potential firing as the voltage becomes more negative (for an action potential to fire, a positive voltage threshold must be reached). GABA is synthesized from glutamate neurotransmitters by the enzyme glutamate decarboxylase.
      • Glutamatergic neurons—glutamate. Glutamate is one of two primary excitatory amino acid neurotransmitters, along with aspartate. Glutamate receptors are one of four categories, three of which are ligand-gated ion channels and one of which is a G-protein coupled receptor (often referred to as GPCR).
        and Kainate receptors function as cation channels permeable to Na + cation channels mediating fast excitatory synaptic transmission. receptors are another cation channel that is more permeable to Ca 2+ . The function of NMDA receptors depend on glycine receptor binding as a co-agonist within the channel pore. NMDA receptors do not function without both ligands present.
  • Metabotropic receptors, GPCRs modulate synaptic transmission and postsynaptic excitability.
    • Dopaminergic neurons—dopamine. Dopamine is a neurotransmitter that acts on D1 type (D1 and D5) Gs-coupled receptors, which increase cAMP and PKA, and D2 type (D2, D3, and D4) receptors, which activate Gi-coupled receptors that decrease cAMP and PKA. Dopamine is connected to mood and behavior and modulates both pre- and post-synaptic neurotransmission. Loss of dopamine neurons in the substantia nigra has been linked to Parkinson's disease. Dopamine is synthesized from the amino acid tyrosine. Tyrosine is catalyzed into levadopa (or L-DOPA) by tyrosine hydroxlase, and levadopa is then converted into dopamine by the aromatic amino acid decarboxylase.
    • Serotonergic neurons—serotonin. Serotonin (5-Hydroxytryptamine, 5-HT) can act as excitatory or inhibitory. Of its four 5-HT receptor classes, 3 are GPCR and 1 is a ligand-gated cation channel. Serotonin is synthesized from tryptophan by tryptophan hydroxylase, and then further by decarboxylase. A lack of 5-HT at postsynaptic neurons has been linked to depression. Drugs that block the presynaptic serotonin transporter are used for treatment, such as Prozac and Zoloft.
    • Purinergic neurons—ATP. ATP is a neurotransmitter acting at both ligand-gated ion channels (P2X receptors) and GPCRs (P2Y) receptors. ATP is, however, best known as a cotransmitter. Such purinergic signalling can also be mediated by other purines like adenosine, which particularly acts at P2Y receptors.
    • Histaminergic neurons—histamine. Histamine is a monoamine neurotransmitter and neuromodulator. Histamine-producing neurons are found in the tuberomammillary nucleus of the hypothalamus. [17] Histamine is involved in arousal and regulating sleep/wake behaviors.

    Multimodel Classification Edit

    Since 2012 there has been a push from the cellular and computational neuroscience community to come up with a universal classification of neurons that will apply to all neurons in the brain as well as across species. this is done by considering the 3 essential qualities of all neurons: electrophysiology, morphology, and the individual transcriptome of the cells. besides being universal this classification has the advantage of being able to classify astrocytes as well. A method called Patch-Seq in which all 3 qualities can be measured at once is used extensively by the Allen Institute for Brain Science. [18]

    Neurons communicate with each other via synapses, where either the axon terminal of one cell contacts another neuron's dendrite, soma or, less commonly, axon. Neurons such as Purkinje cells in the cerebellum can have over 1000 dendritic branches, making connections with tens of thousands of other cells other neurons, such as the magnocellular neurons of the supraoptic nucleus, have only one or two dendrites, each of which receives thousands of synapses.

    Synapses can be excitatory or inhibitory, either increasing or decreasing activity in the target neuron, respectively. Some neurons also communicate via electrical synapses, which are direct, electrically conductive junctions between cells. [19]

    When an action potential reaches the axon terminal, it opens voltage-gated calcium channels, allowing calcium ions to enter the terminal. Calcium causes synaptic vesicles filled with neurotransmitter molecules to fuse with the membrane, releasing their contents into the synaptic cleft. The neurotransmitters diffuse across the synaptic cleft and activate receptors on the postsynaptic neuron. High cytosolic calcium in the axon terminal triggers mitochondrial calcium uptake, which, in turn, activates mitochondrial energy metabolism to produce ATP to support continuous neurotransmission. [20]

    An autapse is a synapse in which a neuron's axon connects to its own dendrites.

    The human brain has some 8.6 x 10 10 (eighty six billion) neurons. [21] Each neuron has on average 7,000 synaptic connections to other neurons. It has been estimated that the brain of a three-year-old child has about 10 15 synapses (1 quadrillion). This number declines with age, stabilizing by adulthood. Estimates vary for an adult, ranging from 10 14 to 5 x 10 14 synapses (100 to 500 trillion). [22]

    In 1937 John Zachary Young suggested that the squid giant axon could be used to study neuronal electrical properties. [23] It is larger than but similar to human neurons, making it easier to study. By inserting electrodes into the squid giant axons, accurate measurements were made of the membrane potential.

    The cell membrane of the axon and soma contain voltage-gated ion channels that allow the neuron to generate and propagate an electrical signal (an action potential). Some neurons also generate subthreshold membrane potential oscillations. These signals are generated and propagated by charge-carrying ions including sodium (Na + ), potassium (K + ), chloride (Cl − ), and calcium (Ca 2+ ).

    Several stimuli can activate a neuron leading to electrical activity, including pressure, stretch, chemical transmitters, and changes of the electric potential across the cell membrane. [24] Stimuli cause specific ion-channels within the cell membrane to open, leading to a flow of ions through the cell membrane, changing the membrane potential. Neurons must maintain the specific electrical properties that define their neuron type. [25]

    Thin neurons and axons require less metabolic expense to produce and carry action potentials, but thicker axons convey impulses more rapidly. To minimize metabolic expense while maintaining rapid conduction, many neurons have insulating sheaths of myelin around their axons. The sheaths are formed by glial cells: oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. The sheath enables action potentials to travel faster than in unmyelinated axons of the same diameter, whilst using less energy. The myelin sheath in peripheral nerves normally runs along the axon in sections about 1 mm long, punctuated by unsheathed nodes of Ranvier, which contain a high density of voltage-gated ion channels. Multiple sclerosis is a neurological disorder that results from demyelination of axons in the central nervous system.

    Some neurons do not generate action potentials, but instead generate a graded electrical signal, which in turn causes graded neurotransmitter release. Such non-spiking neurons tend to be sensory neurons or interneurons, because they cannot carry signals long distances.

    Neural coding is concerned with how sensory and other information is represented in the brain by neurons. The main goal of studying neural coding is to characterize the relationship between the stimulus and the individual or ensemble neuronal responses, and the relationships among the electrical activities of the neurons within the ensemble. [26] It is thought that neurons can encode both digital and analog information. [27]

    The conduction of nerve impulses is an example of an all-or-none response. In other words, if a neuron responds at all, then it must respond completely. Greater intensity of stimulation, like brighter image/louder sound, does not produce a stronger signal, but can increase firing frequency. [28] : 31 Receptors respond in different ways to stimuli. Slowly adapting or tonic receptors respond to steady stimulus and produce a steady rate of firing. Tonic receptors most often respond to increased intensity of stimulus by increasing their firing frequency, usually as a power function of stimulus plotted against impulses per second. This can be likened to an intrinsic property of light where greater intensity of a specific frequency (color) requires more photons, as the photons can't become "stronger" for a specific frequency.

    Other receptor types include quickly adapting or phasic receptors, where firing decreases or stops with steady stimulus examples include skin which, when touched causes neurons to fire, but if the object maintains even pressure, the neurons stop firing. The neurons of the skin and muscles that are responsive to pressure and vibration have filtering accessory structures that aid their function.

    The pacinian corpuscle is one such structure. It has concentric layers like an onion, which form around the axon terminal. When pressure is applied and the corpuscle is deformed, mechanical stimulus is transferred to the axon, which fires. If the pressure is steady, stimulus ends thus, typically these neurons respond with a transient depolarization during the initial deformation and again when the pressure is removed, which causes the corpuscle to change shape again. Other types of adaptation are important in extending the function of a number of other neurons. [29]

    The German anatomist Heinrich Wilhelm Waldeyer introduced the term neuron in 1891, [30] based on the ancient Greek νεῦρον neuron 'sinew, cord, nerve'. [31]

    The word was adopted in French with the spelling neurone. That spelling was also used by many writers in English, [32] but has now become rare in American usage and uncommon in British usage. [33] [31]


    The inhibition of high-voltage-activated calcium current by activation of MrgC11 involves phospholipase C-dependent mechanisms

    High-voltage-activated (HVA) calcium channels play an important role in synaptic transmission. Activation of Mas-related G-protein-coupled receptor subtype C (MrgC mouse MrgC11, rat homolog rMrgC) inhibits HVA calcium current (ICa) in small-diameter dorsal root ganglion (DRG) neurons, but the intracellular signaling cascade underlying MrgC agonist-induced inhibition of HVA ICa in native DRG neurons remains unclear. To address this question, we conducted patch-clamp recordings in MrgA3-eGFP-wild-type mice, in which most MrgA3-eGFP(+) DRG neurons co-express MrgC11 and can be identified for recording. We found that the inhibition of HVA ICa by JHU58 (0.001-100nM, a dipeptide, MrgC-selective agonist) was significantly reduced by pretreatment with a phospholipase C (PLC) inhibitor (U73122, 1μM), but not by its inactive analog (U73343) or vehicle. Further, in rats that had undergone spinal nerve injury, pretreatment with intrathecal U73122 nearly abolished the inhibition of mechanical hypersensitivity by intrathecal JHU58. The inhibition of HVA ICa in MrgA3-eGFP(+) neurons by JHU58 (100nM) was partially reduced by pretreatment with a Gβγ blocker (gallein, 100μM). However, applying a depolarizing prepulse and blocking the Gαi and Gαs pathways with pertussis toxin (PTX) (0.5μg/mL) and cholera toxin (CTX) (0.5μg/mL), respectively, had no effect. These findings suggest that activation of MrgC11 may inhibit HVA ICa in mouse DRG neurons through a voltage-independent mechanism that involves activation of the PLC, but not Gαi or Gαs, pathway.

    Sleutelwoorde: MrgC PLC calcium channel dorsal root ganglion pain.

    Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

    Syfers

    Fig. 1. Pertussis toxin (PTX) does not…

    Fig. 1. Pertussis toxin (PTX) does not block JHU58-induced inhibition of high-voltage-activated (HVA) calcium currents…

    Fig. 2. Pertussis toxin (PTX) does not…

    Fig. 2. Pertussis toxin (PTX) does not reduce BAM8-22–induced inhibition of high-voltage-activated (HVA) calcium currents…

    Fig. 3. JHU58-induced inhibition of high-voltage-activated (HVA)…

    Fig. 3. JHU58-induced inhibition of high-voltage-activated (HVA) calcium currents ( ek Ca ) in MrgA3-eGFP…

    Fig. 4. Effects of gallein and prepulse…

    Fig. 4. Effects of gallein and prepulse stimulation on JHU58-induced inhibition of high-voltage-activated (HVA) calcium…

    Fig. 5. Cholera toxin (CTX) does not…

    Fig. 5. Cholera toxin (CTX) does not block JHU58-induced inhibition of high-voltage-activated (HVA) calcium currents…

    Fig. 6. U73122 reduces JHU58-induced inhibition of…

    Fig. 6. U73122 reduces JHU58-induced inhibition of neuropathic mechanical hypersensitivity


    Songbird neurons for advanced cognition mirror the physiology of mammalian counterparts

    University of Massachusetts Amherst neuroscientists examining genetically identified neurons in a songbird's forebrain discovered a remarkable landscape of physiology, auditory coding and network roles that mirrored those in the brains of mammals.

    The research, published May 13 in Huidige Biologie, advances insight into the fundamental operation of complex brain circuits. It suggests that ancient cell types in the pallium -- the outer regions of the brain that include cortex -- most likely retained features over millions of years that are the building blocks for advanced cognition in birds and mammals.

    "We as neuroscientists are catching on that birds can do sophisticated things and they have sophisticated circuits to do those things," says behavioral neuroscientist Luke Remage-Healey, associate professor of psychological and brain sciences and senior author of the paper.

    For the first time, the team of neuroscientists, including lead author Jeremy Spool, who worked as a National Institutes of Health (NIH) postdoctoral fellow in Remage-Healey's lab, used viral optogenetics to define the molecular identities of excitatory and inhibitory cell types in zebra finches (Taeniopygia guttata) and match them to their physiological properties.

    "In the songbird community, we've had a hunch for a long time that when we record the electrical signatures of these two cell types, we say -- 'that's a putative excitatory neuron, that's a putative inhibitory neuron.' Now we know that these features are grounded in molecular truth," Remage-Healey says. "Without being able to pinpoint the cell types with these viruses, we wouldn't be able to learn how the cell and network features bear resemblance to those in mammals, because the brain architectures are so different."

    The research team used viruses from a collection curated by co-author Yoko Yazaki-Sugiyama at the Okinawa Institute of Science and Technology in Japan to conduct viral optogenetic experiments in the brain. With optogenetics, the team used flashes of light to manipulate one cell type independent of the other. The team targeted excitatory vs. inhibitory neurons (using CaMKII? and GAD1 promoters, respectively) in the zebra finch auditory pallium to test predictions based on the mammalian pallium.

    "There's so much work out there on the physiology of these different cell types in the mammalian cortex that we were able to line up a series of predictions about what features birds may or may not have," Spool says.

    The CaMKII? and GAD1 populations in the songbird were distinct "in exactly the proportions you would expect from the mammalian brain," Spool says. With the cell type populations isolated, the researchers then examined systematically whether each population would correspond to the physiology of their mammalian counterparts.

    "As we kept moving forward, again and again these cell populations were acting as if they were essentially from the mammalian cortex in a lot of physiological ways," Spool says.

    Remage-Healey adds, "The correspondence between the cortex in mammals and what we're pulling out with molecularly identified cell types in birds is pretty striking."

    In both birds and mammals, these neurons are thought to support advanced cognitive functions, such as memory, individual recognition and associative learning, Spool says.

    Remage-Healey says the research, supported by NIH grants, helps delineate "the basic nuts and bolts of how the brain operates." Knowing the nuts and bolts builds foundations necessary to develop breakthroughs that could lead to neurological interventions for brain disorders.

    "This can help us figure out what brain diversity is out there by unpacking these circuits and the ways they can go awry," Remage-Healey says.


    Kyk die video: Natuurkunde uitleg elektriciteit 1: Stroomsterkte (Junie 2022).


Kommentaar:

  1. Voodooshura

    In my opinion, this is a big mistake.

  2. Iwdael

    In my opinion it already was discussed, use search.

  3. Taidhgin

    Uhahahah

  4. Lee

    Fantastiese tema, baie aangenaam :)

  5. Choviohoya

    Dit lyk vir my uitstekende idee is



Skryf 'n boodskap