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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Phillips, Keith Geoffrey
Languages: English
Types: Doctoral thesis
Subjects: RC0321

Classified by OpenAIRE into

mesheuropmc: musculoskeletal, neural, and ocular physiology, nervous system
Studies in GluRl knockout mice have shown that neocortical LTP consist of both pre- and post-synaptic components that rely on nitric oxide and GluRl respectively (Hardingham and Fox, 2006). Given that GluRl knockout also show hippocampal LTP (Hoffmann et al., 2002) I hypothesised that the residual LTP might depend on nitric oxide. I have found that hippocampal LTP can be induced in GluRl knockout with purely orthodromic stimuli in mature mice (>8weeks) and that a theta-burst protocol was effective at inducing LTP while 100Hz stimulation was not. I found that only theta-burst stimulation produced reliable post-synaptic spikes, while 100Hz stimulation produced relatively few spikes. Inhibition of post-synaptic somatic spikes with local TTX application prevented LTP in the GluRl knockout mice. Theta-burst induced LTP in GluRl knockout was almost entirely nitric oxide dependent and involved both nitric oxide synthase 1 and nitric oxide synthase 3 isoforms. Finally, I also found that somatic spike production was also necessary for a nitric oxide dependent form of LTP in wild-type mice, which made up approximately 50% of the potentiation at 2 hours post-tetanus. I conclude that nitric oxide dependent LTP can be produced by physiologically relevant theta-burst stimuli because this protocol evokes reliable action potentials. Since this form of activity occurs during learning it could be relevant to memory formation in GluRl knockout and wild-type mice.
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    • Andrisfalvy BK, Smith MA, Borchardt T, Sprengel R, Magee JC (2003) Im ­ paired regulation o f synaptic strength in hippocampal neurons from G luRl-deficient mice. J Physiol 552:35-45.
    • Bayazitov IT, Richardson RJ, Fricke RG, Zakharenko SS (2007) Slow presynaptic and fast postsynaptic com ponents o f com pound long-term potentiation. J Neurosci 27:11510-11521.
    • Blackshaw S, Eliasson MJ, Sawa A, Watkins CC, Krug D, Gupta A, Arai T, Ferrante RJ, Snyder SH (2003) Species, strain and developmental variations in hippocampal neuronal and endothelial nitric oxide synthase clarify discrepancies in nitric oxide-dependent synaptic plasticity. Neuroscience 119:979-990.
    • Bliss TV, Lomo T (1973) Long-lasting potentiation o f synaptic transmission in the dentate area o f the anaesthetized rabbit following stimulation o f the perforant path. J Physiol 232:331-356.
    • Chetkovich DM, Klann E, Sweatt JD (1993) Nitric oxide synthaseindependent long-term potentiation in area CA1 o f hippocampus. N euroreport 4:919-922.
    • Eliasson MJ, Blackshaw S, Schell MJ, Snyder SH (1997) Neuronal nitric o x ­ ide synthase alternatively spliced forms: prominent functional localizations in the brain. Proc Natl Acad Sci U S A 94:3396-3401.
    • Golding NL, Staff NP, Spruston N (2002) Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature 418:326-331.
    • Gribkoff VK, Lum-Ragan JT (1992) Evidence for nitric oxide synthase inhibitor-sensitive and insensitive hippocampal synaptic potentiation. J Neurophysiol 68:639-642.
    • Haley JE, Wilcox GL, Chapman PF (1992) The role o f nitric oxide in hippocampal long-term potentiation. Neuron 8:211-216.
    • Haley JE, Malen PL, Chapman PF (1993) Nitric oxide synthase inhibitors block long-term potentiation induced by weak but not strong tetanic stimulation at physiological brain temperatures in rat hippocampal slices. Neurosci Lett 160:85-88.
    • Hardingham N, Fox K (2006) The role o f nitric oxide and GluRl in presynaptic and postsynaptic com ponents o f neocortical potentiation. JN eurosci 26:7395-7404.
    • Hawkins RD, Son H, Arancio O (1998) Nitric oxide as a retrograde messenger during long-term potentiation in hippocampus. Prog Brain Res 118:155-172.
    • Hoffman DA, Sprengel R, Sakmann B (2002) Molecular dissection o f hippocampal theta-burst pairing potentiation. Proc Natl Acad Sci U S A 99:7740-7745.
    • Hblscher C (1997) Nitric oxide, the enigmatic neuronal messenger: its role in synaptic plasticity. Trends Neurosci 20:298-303.
    • Holscher C (2002) Different strains o f rats show different sensitivity to block o f long-term potentiation by nitric oxide synthase inhibitors. Eur J Pharmacol 457:99-106.
    • Huang PL, Dawson TM, Bredt DS, Snyder SH, Fishman MC (1993) Targeted disruption o f the neuronal nitric oxide synthase gene. Cell 75:1273-1286.
    • Huang Y, Man HY, Sekine-Aizawa Y, Han Y, Juluri K, Luo H, Cheah J, Lowenstein C, Huganir RL, Snyder SH (2005) S-nitrosylation o f N-ethylmaleimide sensitive factor mediates surface expression o f AMPA receptors. Neuron 46:533-540.
    • Ishida A, Shigeri Y, Tatsu Y, Uegaki K, Kameshita I, Okuno S, Kitani T, Yumoto N, Fujisawa H (1998) Critical amino acid residues o f AIP, a highly specific inhibitory peptide o f calmodulin-dependent protein kinase II. FEBS Lett 427:115-118.
    • Jensen V, Kaiser KM, Borchardt T, Adelmann G, Rozov A, Burnashev N, Brix C, Frotscher M, Andersen P, Hvalby O, Sakmann B, Seeburg PH, Sprengel R (2003) A juvenile form o f postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A. J Physiol 553:843-856.
    • Kantor DB, Lanzrein M, Stary SJ, Sandoval GM, Smith WB, Sullivan BM, Davidson N, Schuman EM (1996) A role for endothelial NO synthase in LTP revealed by adenovirus-mediated inhibition and rescue. Science 274:1744-1748.
    • Lisman J, Raghavachari S (2006) A unified model o f the presynaptic and postsynaptic changes during LTP at CA1 synapses. Sci STKE 2006:rel 1.
    • Mack V, Burnashev N, Kaiser KM, Rozov A, Jensen V, Hvalby O, Seeburg PH, Sakmann B, Sprengel R (2001) Conditional restoration o f hippocampal synaptic potentiation in Glur-A-deficient mice. Science 292:2501-2504.
    • Malenka RC, Kauer JA, Perkel DJ, Mauk MD, Kelly PT, Nicoll RA, Waxham MN (1989) An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation. Nature 340:554-557.
    • Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103-126.
    • Malinow R, Tsien RW (1990) Presynaptic enhancement shown by wholecell recordings o f long-term potentiation in hippocampal slices. Nature 346:177-180.
    • O 'Dell TJ, Hawkins RD, Kandel ER, Arancio O (1991) Tests o f the roles o f two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proc Natl Acad Sci U S A 88:11285-11289.
    • O 'Dell TJ, Huang PL, Dawson TM, Dinerman JL, Snyder SH, Kandel ER, Fishman MC (1994) Endothelial NOS and the blockade o f LTP by NOS inhibitors in mice lacking neuronal NOS. Science 265:542-546.
    • Raymond CR (2008) Different requirements for action potentials in the induction o f different forms o f long-term potentiation. J Physiol 586:1859-1865.
    • Sanderson DJ, Good MA, Seeburg PH, Sprengel R, Rawlins JN, Bannerman DM (2008) The role of the GluR-A (G luRl) AMPA receptor subunit in learning and memory. Prog Brain Res 169:159-178.
    • Schmitt WB, Deacon RM, Seeburg PH, Rawlins JN, Bannerman DM (2003) A within-subjects, within-task demonstration o f intact spatial reference memory and impaired spatial working memory in glutamate receptor-Adeficient mice. J Neurosci 23:3953-3959.
    • Schmitt WB, Sprengel R, Mack V, Draft RW, Seeburg PH, Deacon RM, Rawlins JN, Bannerman DM (2005) Restoration o f spatial working memory by genetic rescue o f GluR-A-deficient mice. Nat Neurosci 8:270-272.
    • Schulz PE, Cook EP, Johnston D (1994) Changes in paired-pulse facilitation suggest presynaptic involvement in long-term potentiation. J Neurosci 14:5325-5337.
    • Son H, Hawkins RD, Martin K, Kiebler M, Huang PL, Fishman MC, Kandel ER (1996) Long-term potentiation is reduced in mice that are doubly mutant in endothelial and neuronal nitric oxide synthase. Cell 87:1015-1023.
    • Stanton PK, Winterer J, Zhang XL, Muller W (2005) Imaging LTP o f presynaptic release o f F M 1-43 from the rapidly recycling vesicle pool of Schaffer collateral-CAl synapses in rat hippocampal slices. Eur JNeurosci 22:2451-2461.
    • Wright N, Glazewski S, Hardingham N, Phillips K, Pervolaraki E, Fox K (2008) Laminar analysis o f the role played by GluRl in experiencedependent and synaptic depression o f sensory responses in barrel cortex. Nat Neurosci 11:1140-1142.
    • Zamanillo D, Sprengel R, Hvalby O, Jensen V, Burnashev N, Rozov A, Kaiser KM, Koster HJ, Borchardt T, Worley P, Liibke J, Frotscher M, Kelly PH, Sommer B, Andersen P, Seeburg PH, Sakmann B (1999) Importance o f AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 284:1805-1811.
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