Hermosolu 1. Hermosolu. Hermosolu 2. Hermosolu 3

Transkriptio

1 Hermosolu 1 Hermosolu Ominaisuudet ärtyvyys sähköisen signaalin kuljetus proteiinit mukana signaalin muodostumisessa ja kuljetuksessa aktiopotentiaali (pitkän matkan kuljetus) Neuronien väliset yhteydet sähköinen synapsi kemiallinen: signaalimolekyylinä neurotransmitteri Hermosolu 2 Hermosolu 3 neurotransmitteri vaikuttaa kohteessa reseptorin kautta muuttaa ionikanavan ominaisuuksia toisiolähetin synteesi: adenylaattisyklaasi camp Gliasolut eivät johda sähköisiä tai kemiallisia signaaleja aineenvaihdunta rakenteellinen tuki eräät toimivat rakennustelineinä ja ohjailussa hermoston kehityksen aikana Oppiminen yksinkertaisissa systeemeissä pienen neuronijoukon ominaisuuksissa tapahtuvia muutoksia

2 Hermosolun rakenne 1 Hermosolun rakenne 2 solukeskus dendriitti, kuljettaa viestejä hermosolulle aksoni, kuljettaa viestejä hermosolusta pois ja liittyy toisiin soluihin, yhdellä aksonilla voi olla yhteyksiä moneen kohdesoluun dendriittimäärä useimmiten suurempi kuin aksonimäärä, esim. pikkuaivojen dendriittipuussa Purkinjen soluissa yli input-liittymää muista soluista, aksonit kuitenkin kuljettavat kauas samat soluorganellit kuin muillakin soluilla: runsaasti mitokondrioita ja ribosomeja käyttävät siis runs. energiaa ja syntetisoivat proteiineja aivot n. 2 % ruumiin painosta, mutta käyttävät n. 20 % energiasta aksoneissa ja dendriiteissä runs. sytoskeletonin proteiineja: dendriiteissä mikrotubuluksia, Hermosolun rakenne 3 Hermosolutyypit ja neuronien luokittelu aksoneissa mikrotubuluksia ja neurofilamentteja sekä neuronispesifisiä välifilamentteja Hermosoluverkko aivoissa neuroneja ja jokaisella neuronilla on keskimäärin 10 4 synapsia synapsin verkko kertainen määrä hermotukisoluja bipolaarinen: dendriitti ja aksoni vastakkaisilla puolilla multipolaarinen: yleisin, muoto ja dendriittien lukumäärä vaihtelevat, pyramidi ja tähtimuoto yleisimmät unipolaarinen: vain aksoni, tyypillisiä kehittyvässä hermokudoksessa pseudounipolaarinen: yleisempi kuin unip., aksoni ja dendriitti kulkevat yhdessä jonkin matkaa

3 Gliasolut Dendrites Dendrites Schwann cell Gliasolujen luokittelu: astrosyytti: keskushermoston yleisin solutyyppi oligodendrosyytti tai Schwannin solu perifeerisessä kudoksessa kiertyy hermosolun ympärille ja muod. myeliinitupen Fig. 1 Intrinsic epigenetic mechanisms converge with extrinsic signals to promote astrocyte fate from NPCs. Schwann cell Nucleus M R Freeman Science 2010;330: Published by AAAS

4 Kuvateksti edelliseen diaan Fig. 2 Astrocyte diversity is generated by production from unique spatial domains. Intrinsic epigenetic mechanisms converge with extrinsic signals to promote astrocyte fate from NPCs. (A) In early NPCs, chromatin is open at the neurogenin1 and neurogenin2 (ngn1 and 2) loci, Wnt signals can activate their expression, and neurogenins promote neuronal fate and inhibit astrocyte fate. In postnatal NPCs, the ngn1 and 2 loci have been methylated and bound by PcG, chromatin is closed, Wnt-dependent ngn1 and 2 expression is suppressed, and astrocyte fate is in turn derepressed. (B) Astrocyte genes are methylated during embryonic stages, which closes local chromatin; this is maintained by DNMT1, and astrocyte fate is suppressed, despite the presence of low levels of the proastrocyte factor CT-1. At the switch from NPC production of neurons to astrocytes, Ngn+ neurons release additional CT-1, which activates JAK-STAT signaling, and also activates Notch signaling (likely through JAG1 or DLL2), which activates NFIA, an inhibitor of Dnmt1 activity. Positive JAK-STAT signaling, coupled with opening of chromatin at astrocyte gene loci, promotes astrocyte fate. Published by AAAS M R Freeman Science 2010;330: Fig. 3 Astrocyte morphology is far more complex than initially appreciated. Kuvateksti edelliseen diaan Astrocyte diversity is generated by production from unique spatial domains. (A) A schematic illustrating VA1, VA2, and VA3 domains of the spinal cord white matter astrocytes and expression domains of Reelin and Slit1. (B) A homeodomain code that controls the generation of neuronal diversity is reused during astrocyte specification to promote white matter astrocyte diversity. [(A) and (B) are adapted from (12)] M R Freeman Science 2010;330: Published by AAAS

5 Kuvateksti edelliseen diaan Fig. 4 Coordination of astrocyte morphological growth and refinement with synapse formation. Astrocyte morphology is far more complex than initially appreciated. Astrocytes in an organotypic slice preparation labeled with the common marker GFAP (red) overlaid with a single astrocyte transfected with the membrane marker Lck-GFP (green fluorescent protein). Arrow indicates GFAP label of Lck-GFP marked astrocyte. [From (53) with permission from Elsevier] M R Freeman Science 2010;330: Published by AAAS Kuvateksti edelliseen diaan Neuronin liittyminen gliasoluun Coordination of astrocyte morphological growth and refinement with synapse formation. (A) Although most neurons are made during embryonic stages, the major waves of synaptogenesis follow and depend on astrocyte production. The timing of astrocyte growth and morphological refinement overlaps significantly with this window of synaptogenesis. (B) Astrocytes initially extend large, filopodial processes that overlap significantly with neighboring astrocytes; however, by postnatal day 21, astrocytes refine their morphology to occupy unique spatial domains and elaborate fine processes that closely associate with synapses. (C) A complex interrelation exists between synapses and astrocyte processes. Eph or ephrin signaling can bidirectionally control astrocyte features, as well as spine morphology (see text). Cell body Presynaptic axon terminal Synapse Postsynaptic dendrite Cell body (initial segment) Collateral Nucleus hillock Myelin sheath terminal veriaivoeste, blood brain barrier

6 Hermosoluverkko Ependymal cell Lepopotentiaali Interneurons Node Oligodendrocyte Microglia Capillary Astrocyte lepopotentiaali riippuvainen ionikanavien selektiivisyydestä ja ionipumpuista solukalvon ulkopuoli on positiivinen koska: 1. Na-K-pumppu ylläpitää varausgradienttia: käyttää energiaa (ATP) pumpatakseen Na + ulos ja K + sisään (1 mooli ATP:tä 3 Na + ulos ja 2 K + sisään) 2. solukalvon selektiivisyys Na + ja K + ioneille Ekstrasellulaarinen mittaus lasinen kapillaarielektrodi on tavallisin potentiaalieroa mitataan esim. oskilloskoopilla mikroelektrodien välillä näkyvä jänniteero tuottaa aktiopotentiaalin (usein rekisteröi-dään summapoten-tiaalina) spiket voidaan rekisteröidä myös tietokoneelle esim. Spike 2 ohjelmalla intrasellulaarinen mittaaminen vaativampaa Microelectrodes Time (msec)

7 Aktiopotentiaali 1 Aktiopotentiaali 2 OUTSIDE CELL Sodiumpotassium pump Voltage-gated Na + channels open and Na + enters the axon Trigger zone [K + ] 5 mm [Na + ] [Cl - ] 150 mm 120 mm OUTSIDE CELL plasmamembrane A graded potential above threshold reaches the trigger zone INSIDE CELL [K + ] 150 mm [Na] 15 mm [Cl- ] 10 mm [A - ] 100 mm INSIDE CELL Aktiopotentiaali 3 Aktiopotentiaali 4 Na + entry depolarizes the membrane, which opens additional Na + channels Refactory region Active regions Inactive Positive charge flows into adjacent sections of the axon by local current flow The trigger zone is in its refactory period. K + gates have opened and the Na + inactivation gates have closed. Loss of K + from the cytoplasm repolarizes the membrane In the distal parts of the axon, local current flow from the active region causes new sections of the membrane to depolarize

8 Neurotransmitterin synteesi ja kuljetus Kemiallinen synapsi 2 6. Old membrane components digested in lysosomes Action potential terminal 5. Retrograde fast axonal transport Synaptic vesicle Soma Rough endoplasmic reticulum Golgi body 1. Peptides synthesized and packed 2. Fast axonal transport along microtubule network 3. Vesicle contents released by exocytosis Voltagegated Ca 2+ channel Ca 2+ Docking protein Postsynaptic cell Receptor Myeliinitupellinen neuroni 1 Dendrites Myeliinitupellinen neuroni 2 Site of injury Nucleus of Schwann cell Proximal stump Distal stump terminal Myelin

9 Schwannin solu ja Ranvierin kurouma Cytosol of Schwann cell Node of Ranvier Miten neurotransmitterien vapautuminen liittyy muistiin? Plasma membrane of axon NMDA = N-methyl-Daspartaatti, reseptorit jotka sitovat tätä ligandia ja toiset eivät yksittäinen stimulus vapauttaa glutamaattia Mg 2+ blokeeraa Pitkäkestoisessa muistissa NMDA-glutamaattireseptorin (a) depolarisaatio johtaa kalvopotentiaalimuutoksiin ja Ca 2+ Ca sitoutuu calmoduliiniin signaali Plasma membrane of Schwann cell Glutamate from CA3 neuron Metabotropic glutamate receptor Voltage-gated Ca 2+ channel NMDA-reseptori Normal synaptic transmission Mg 2+ K + NMDA glutamate receptor CA3 neuron Non-NMDA glutamate receptor Cendritic spine relating to or being a receptor for glutamate that when complexed with G protein triggers increased production of certain intracellular messengers <metabotropic glutamate receptors The hippocampus is perhaps the most studied structure in the brain. together with the adjacent Amygdyla, it forms the central axis of the Limbic System. It is critical to spatial learning and awareness, navigation, episodic/event memory, associational recollection... and much more. Hippocampus Dendritic shaft

10 Afferents from the entorhinal cortex (EC) synapse onto distal dendrites, whereas axons from CA3 neurons project to proximal dendrites. (A) Synaptic activation (1 Hz) of proximal dendrites induces a regular firing response at the cell body of the model cell. (B) Strong (theta-burst) stimulation of EC inputs coinciding with CA3 stimulation evokes calcium spikes in the distal dendrites, the occurrence of which initiates bursts of action potentials (APs), and facilitates the somatic response. (C) Temporally distant activation of EC with subthreshold bursts (400 ms after the CA3 input) prevents the initiation of somatic action potentials for several seconds, thus weakening the somatic response. Green dots, excitatory inputs; red dots, inhibitory inputs. The EC is the main interface between the hippocampus and neocortex. Kyriaki Sidiropoulou, Eleftheria Kyriaki Pissadaki & Panayiota Poirazi EMBO reports (2006) 7, Pitkäkestoinen (muisti) Induction of long-term potentiation (LTP) Prolonged transmitter release Ca 2+ Protein kinase C Na + Increased Ca 2+ concentration Calmodulin Ca 2+ calmodulin Tyrosine kinase kinase Retrograde signal generator Signaali välittyy postsynaptiselta puolelta presynaptiselle puolelle Presynaptic spread of retrograde signals associated with the induction of LTP. (A) Schematic diagram showing the direction of spread of potentiation signals in the presynaptic cytoplasm after induction of LTP at hippocampal synapses in cell cultures (see re... Tao H W, Poo M PNAS 2001;98: NMDA receptor-dependent transport from recycling endosomes may provide a unifying cellular mechanism linking functional and structural plasticity at glutamatergic synapses. Work from several laboratories has established that LTP-inducing stimuli promote the physical insertion of AMPA receptors at the postsynaptic membrane, leading to an increase in AMPA receptor-mediated transmission at excitatory synapses (Malenka and Nicoll, 1999).

11 Article Plasticity-Induced Growth of Dendritic Spines by Exocytic Trafficking from Recycling Endosomes Mikyoung Park 1, Jennifer M. Salgado 3, Linnaea Ostroff 3, Thomas D. Helton 1, Camenzind G. Robinson 1, 2, Kristen M. Harris 3, 4 and Michael D. Ehlers1, 2,, 1 Department of Neurobiology, Duke University Medical Center, Durham, North Carolina Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina Department of Neurology, Synapses and Cognitive Neuroscience Center, Medical College of Georgia, Augusta, Georgia Center for Learning and Memory, Section of Neurobiology, The University of Texas at Austin, Austin, Texas Received 30 May 2006; revised 14 September 2006; accepted 27 September Published: December 6, Available online 6 December They're Plastic, but They Recycle Neuron, Volume 52, Issue 5, 7 December 2006, Pages 746- Referred to by: 748 Shelley Halpain SummaryPlus Full Text + Links PDF (60 K) Summary Dendritic spines are micron-sized membrane protrusions receiving most excitatory synaptic inputs in the mammalian brain. Spines form and grow during long-term potentiation (LTP) of synaptic strength. However, the source of membrane for spine formation and enlargement is unknown. Here we report that membrane trafficking from recycling endosomes is required for the growth and maintenance of spines. Using live-cell imaging and serial section electron microscopy, we demonstrate that LTP-inducing stimuli promote the mobilization of recycling endosomes and vesicles into spines. Preventing recycling endosomal transport abolishes LTP-induced spine formation. Using a ph-sensitive recycling cargo, we show that exocytosis from recycling endosomes occurs locally in spines, is triggered by activation of synaptic NMDA receptors, and occurs concurrently with spine enlargement. Thus, recycling endosomes provide membrane for activitydependent spine growth and remodeling, defining a novel membrane trafficking mechanism for spine morphological plasticity and providing a mechanistic link between structural and functional plasticity during LTP. Transmittereiden välittymiseen reseptoreissa vaikuttavat ionikanavat ja psykoaktiiviset kemikaalit 1. Curare blokkaa Achreseptorit poikkijuov. lihaksen lamaantuminen Etelä-Amerikan intiaanien myrkkynuolissa (kasvista peräisin) 2. Unettomuus, ahdistuneisuus, depressio, skitsofrenia lääkkeet kemiallinen synapsi sitoutuu transmittergated ionchannels Author Keywords: CELLBIO; MOLNEURO Transmittereiden välittymiseen reseptoreissa Barbituraatit rauhoittavat lääkkeet (Valium, Librium) sit. GABAreseptoreihin tehostavat GABA:n inhibitorisia vaikutuksia alh. konsentraatio avaa Cl-kanavat Ionikanavat molekulaarinen perusta, joiden kautta neuronaalinen viestintä toimii