cGMP Signalling in the Mammalian Brain: Role in Synaptic Plasticity and Behaviour

Part of the Handbook of Experimental Pharmacology book series (HEP, volume 191)

Abstract

The second messenger cyclic guanosine 3′,5′-monophosphate (cGMP) plays a crucial role in the control of cardiovascular and gastrointestinal homeostastis, but its effects on neuronal functions are less established. This review summarizes recent biochemical and functional data on the role of the cGMP signalling pathway in the mammalian brain, with a focus on the regulation of synaptic plasticity, learning, and other complex behaviours. Expression profiling, along with pharmacological and genetic manipulations, indicates important functions of nitric oxide (NO)-sensitive soluble guanylyl cyclases (sGCs), cGMP-dependent protein kinases (cGKs), and cGMP-regulated phosphodiesterases (PDEs) as generators, effectors, and modulators of cGMP signals in the brain, respectively. In addition, neuronal cGMP signalling can be transmitted through cyclic nucleotide-gated (CNG) or hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels. The canonical NO/sGC/cGMP/cGK pathway modulates long-term changes of synaptic activity in the hippocampus, amygdala, cerebellum, and other brain regions, and contributes to distinct forms of learning and memory, such as fear conditioning, motor adaptation, and object recognition. Behavioural studies indicate that cGMP signalling is also involved in anxiety, addiction, and the pathogenesis of depression and schizophrenia. At the molecular level, different cGK isoforms appear to mediate effects of cGMP on presynaptic transmitter release and postsynaptic functions. The cGKs have been suggested to modulate cytoskeletal organization, vesicle and AMPA receptor trafficking, and gene expression via phosphorylation of various substrates including VASP, RhoA, RGS2, hSERT, GluR1, G-substrate, and DARPP-32. These and other components of the cGMP signalling cascade may be attractive new targets for the treatment of cognitive impairment, drug abuse, and psychiatric disorders.

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References

  1. Ajima A, Ito M (1995) A unique role of protein phosphatases in cerebellar long-term depression. Neuroreport 6:297–300PubMedGoogle Scholar
  2. Antonova I, Arancio O, Trillat AC, Wang HG, Zablow L, Udo H, Kandel ER, Hawkins RD (2001) Rapid increase in clusters of presynaptic proteins at onset of long-lasting potentiation. Science 294:1547–1550PubMedGoogle Scholar
  3. Apergis-Schoute AM, Debiec J, Doyere V, LeDoux JE, Schafe GE (2005) Auditory fear conditioning and long-term potentiation in the lateral amygdala require ERK/MAP kinase signaling in the auditory thalamus:a role for presynaptic plasticity in the fear system. J Neurosci 25:5730–5739PubMedGoogle Scholar
  4. Arancio O, Kandel ER, Hawkins RD (1995) Activity-dependent long-term enhancement of transmitter release by presynaptic 3′,5′-cyclic GMP in cultured hippocampal neurons. Nature 376:74–80PubMedGoogle Scholar
  5. Arancio O, Kiebler M, Lee CJ, Lev-Ram V, Tsien RY, Kandel ER, Hawkins RD (1996) Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. Cell 87:1025–1035PubMedGoogle Scholar
  6. Arancio O, Antonova I, Gambaryan S, Lohmann SM, Wood JS, Lawrence DS, Hawkins RD (2001) Presynaptic role of cGMP-dependent protein kinase during long-lasting potentiation. J Neurosci 21:143–149PubMedGoogle Scholar
  7. Barco A, Alarcon JM, Kandel ER (2002) Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell 108:689–703PubMedGoogle Scholar
  8. Barnstable CJ, Wei JY, Han MH (2004) Modulation of synaptic function by cGMP and cGMP-gated cation channels. Neurochem Int 45:875–884PubMedGoogle Scholar
  9. Bear MF, Malenka RC (1994) Synaptic plasticity:LTP and LTD. Curr Opin Neurobiol 4:389–399PubMedGoogle Scholar
  10. Beavo JA, Brunton LL (2002) Cyclic nucleotide research - still expanding after half a century. Nat Rev Mol Cell Biol 3:710–718PubMedGoogle Scholar
  11. Ben-Shahar Y, Robichon A, Sokolowski MB, Robinson GE (2002) Influence of gene action across different time scales on behavior. Science 296:741–744PubMedGoogle Scholar
  12. Biel M, Zong X, Ludwig A, Sautter A, Hofmann F (1999) Structure and function of cyclic nucleotide-gated channels. Rev Physiol Biochem Pharmacol 135:151–171PubMedGoogle Scholar
  13. Blair HT, Schafe GE, Bauer EP, Rodrigues SM, LeDoux JE (2001) Synaptic plasticity in the lateral amygdala:a cellular hypothesis of fear conditioning. Learn Mem 8:229–242PubMedGoogle Scholar
  14. Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232:331–356PubMedGoogle Scholar
  15. Boess FG, Hendrix M, van der Staay FJ, Erb C, Schreiber R, van Staveren W, de Vente J, Prickaerts J, Blokland A, Koenig G (2004) Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology 47:1081–1092PubMedGoogle Scholar
  16. Boulton CL, Southam E, Garthwaite J (1995) Nitric oxide-dependent long-term potentiation is blocked by a specific inhibitor of soluble guanylyl cyclase. Neuroscience 69:699–703PubMedGoogle Scholar
  17. Boxall AR, Garthwaite J (1996) Long-term depression in rat cerebellum requires both NO synthase and NO-sensitive guanylyl cyclase. Eur J Neurosci 8:2209–2212PubMedGoogle Scholar
  18. Bradley J, Zhang Y, Bakin R, Lester HA, Ronnett GV, Zinn K (1997) Functional expression of the heteromeric “olfactory” cyclic nucleotide-gated channel in the hippocampus:a potential effector of synaptic plasticity in brain neurons. J Neurosci 17:1993–2005PubMedGoogle Scholar
  19. Bredt DS, Nicoll RA (2003) AMPA receptor trafficking at excitatory synapses. Neuron 40:361–379PubMedGoogle Scholar
  20. Burette A, Zabel U, Weinberg RJ, Schmidt HH, Valtschanoff JG (2002) Synaptic localization of nitric oxide synthase and soluble guanylyl cyclase in the hippocampus. J Neurosci 22:8961–8970PubMedGoogle Scholar
  21. Buys ES, Sips P, Vermeersch P, Raher MJ, Rogge E, Ichinose F, Dewerchin M, Bloch KD, Janssens S, Brouckaert P (2008) Gender-specific hypertension and responsiveness to nitric oxide in sGCalpha1 knockout mice. Cardiovasc Res 79:179–186PubMedGoogle Scholar
  22. Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM (2007) Nitric oxide in the central nervous system:neuroprotection versus neurotoxicity. Nat Rev Neurosci 8:766–775PubMedGoogle Scholar
  23. Canellada A, Cano E, Sanchez-Ruiloba L, Zafra F, Redondo JM (2006) Calcium-dependent expression of TNF-alpha in neural cells is mediated by the calcineurin/NFAT pathway. Mol Cell Neurosci 31:692–701PubMedGoogle Scholar
  24. Carey M, Lisberger S (2002) Embarrassed, but not depressed:eye opening lessons for cerebellar learning. Neuron 35:223–226PubMedGoogle Scholar
  25. Chen A, Muzzio IA, Malleret G, Bartsch D, Verbitsky M, Pavlidis P, Yonan AL, Vronskaya S, Grody MB, Cepeda I, Gilliam TC, Kandel ER (2003) Inducible enhancement of memory storage and synaptic plasticity in transgenic mice expressing an inhibitor of ATF4 (CREB-2) and C/EBP proteins. Neuron 39:655–669PubMedGoogle Scholar
  26. Chetkovich DM, Klann E, Sweatt JD (1993) Nitric oxide synthase-independent long-term potenti-ation in area CA1 of hippocampus. Neuroreport 4:919–922PubMedGoogle Scholar
  27. Chien WL, Liang KC, Teng CM, Kuo SC, Lee FY, Fu WM (2003) Enhancement of long-term potentiation by a potent nitric oxide-guanylyl cyclase activator, 3-(5-hydroxymethyl-2-furyl)-1-benzyl-indazole. Mol Pharmacol 63:1322–1328PubMedGoogle Scholar
  28. Chien WL, Liang KC, Teng CM, Kuo SC, Lee FY, Fu WM (2005) Enhancement of learning behaviour by a potent nitric oxide-guanylate cyclase activator YC-1. Eur J Neurosci 21:1679–1688PubMedGoogle Scholar
  29. Chung HJ, Steinberg JP, Huganir RL, Linden DJ (2003) Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression. Science 300:1751–1755PubMedGoogle Scholar
  30. Citri A, Malenka RC (2007) Synaptic plasticity:multiple forms, functions, and mechanisms. Neu-ropsychopharmacology 33(1):18–41Google Scholar
  31. Clementi E, Sciorati C, Riccio M, Miloso M, Meldolesi J, Nistico G (1995) Nitric oxide action on growth factor-elicited signals. Phosphoinositide hydrolysis and [Ca2+]i responses are negatively modulated via a cGMP-dependent protein kinase I pathway. J Biol Chem 270:22277–22282PubMedGoogle Scholar
  32. Conti M, Beavo J (2007) Biochemistry and physiology of cyclic nucleotide phosphodiesterases:essential components in cyclic nucleotide signaling. Annu Rev Biochem 76:481–511PubMedGoogle Scholar
  33. Dang MT, Yokoi F, Yin HH, Lovinger DM, Wang Y, Li Y (2006) Disrupted motor learning and long-term synaptic plasticity in mice lacking NMDAR1 in the striatum. Proc Natl Acad Sci USA 103:15254–15259PubMedGoogle Scholar
  34. Dere E, Frisch C, De Souza Silva MA, Godecke A, Schrader J, Huston JP (2001) Unaltered radial maze performance and brain acetylcholine of the endothelial nitric oxide synthase knockout mouse. Neuroscience 107:561–570PubMedGoogle Scholar
  35. Derkach VA, Oh MC, Guire ES, Soderling TR (2007) Regulatory mechanisms of AMPA receptors in synaptic plasticity. Nat Rev Neurosci 8:101–113PubMedGoogle Scholar
  36. de Vente J, Hopkins DA, Markerink-Van Ittersum M, Emson PC, Schmidt HH, Steinbusch HW (1998) Distribution of nitric oxide synthase and nitric oxide-receptive, cyclic GMP-producing structures in the rat brain. Neuroscience 87:207–241PubMedGoogle Scholar
  37. de Vente J, Asan E, Gambaryan S, Markerink-van Ittersum M, Axer H, Gallatz K, Lohmann SM, Palkovits M (2001) Localization of cGMP-dependent protein kinase type II in rat brain. Neu- roscience 108:27–49Google Scholar
  38. DiCicco-Bloom E, Lelievre V, Zhou X, Rodriguez W, Tam J, Waschek JA (2004) Embryonic expression and multifunctional actions of the natriuretic peptides and receptors in the developing nervous system. Dev Biol 271:161–175PubMedGoogle Scholar
  39. Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61PubMedGoogle Scholar
  40. Doreulee N, Brown RE, Yanovsky Y, Godecke A, Schrader J, Haas HL (2001) Defective hip-pocampal mossy fiber long-term potentiation in endothelial nitric oxide synthase knockout mice. Synapse 41:191–194PubMedGoogle Scholar
  41. El-Husseini AE, Bladen C, Vincent SR (1995) Molecular characterization of a type II cyclic GMP-dependent protein kinase expressed in the rat brain. J Neurochem 64:2814–2817PubMedGoogle Scholar
  42. El-Husseini AE, Williams J, Reiner PB, Pelech S, Vincent SR (1999) Localization of the cGMP-dependent protein kinases in relation to nitric oxide synthase in the brain. J Chem Neuroanat 17:45–55PubMedGoogle Scholar
  43. Eliasson MJ, Blackshaw S, Schell MJ, Snyder SH (1997) Neuronal nitric oxide synthase alternatively spliced forms:prominent functional localizations in the brain. Proc Natl Acad Sci USA 94:3396–3401PubMedGoogle Scholar
  44. Erceg S, Monfort P, Hernandez-Viadel M, Rodrigo R, Montoliu C, Felipo V (2005) Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts. Hepatology 41:299–306PubMedGoogle Scholar
  45. Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HH, Stasch JP (2006) NO-independent stimulators and activators of soluble guanylate cyclase:discovery and therapeutic potential. Nat Rev Drug Discov 5:755–768PubMedGoogle Scholar
  46. Feil R, Kemp-Harper B (2006) cGMP signalling:from bench to bedside. Conference on cGMP generators, effectors and therapeutic implications. EMBO Rep 7:149–153PubMedGoogle Scholar
  47. Feil R, Kleppisch T (2008) NO/cGMP-dependent modulation of synaptic transmission. Handb Exp Pharmacol 184:529–560PubMedGoogle Scholar
  48. Feil R, Hartmann J, Luo C, Wolfsgruber W, Schilling K, Feil S, Barski JJ, Meyer M, Konnerth A, De Zeeuw CI, Hofmann F (2003) Impairment of LTD and cerebellar learning by Purkinje cell- specific ablation of cGMP-dependent protein kinase I. J Cell Biol 163:295–302PubMedGoogle Scholar
  49. Feil R, Hofmann F, Kleppisch T (2005a) Function of cGMP-dependent protein kinases in the nervous system. Rev Neurosci 16:23–41Google Scholar
  50. Feil S, Zimmermann P, Knorn A, Brummer S, Schlossmann J, Hofmann F, Feil R (2005b) Distribution of cGMP-dependent protein kinase type I and its isoforms in the mouse brain and retina. Neuroscience 135:863–868Google Scholar
  51. Feil R, Feil S, Franken P, Emmenegger Y, Tafti M, Weindl K, Holter S, Wurst W, Langmesser S, Albrecht U, Foller M, Lang F, Weber S, Hofmann F (2007) New mouse models for the analysis of cGMP signalling. BMC Pharmacol 7:S19Google Scholar
  52. Fiedler B, Lohmann SM, Smolenski A, Linnemuller S, Pieske B, Schroder F, Molkentin JD, Drexler H, Wollert KC (2002) Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP- dependent protein kinase type I in cardiac myocytes. Proc Natl Acad Sci USA 99:11363–11368PubMedGoogle Scholar
  53. Finkbeiner S, Tavazoie SF, Maloratsky A, Jacobs KM, Harris KM, Greenberg ME (1997) CREB:a major mediator of neuronal neurotrophin responses. Neuron 19:1031–1047PubMedGoogle Scholar
  54. Frey U, Krug M, Reymann KG, Matthies H (1988) Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res 452:57–65PubMedGoogle Scholar
  55. Friebe A, Koesling D (2003) Regulation of nitric oxide-sensitive guanylyl cyclase. Circ Res 93:96–105PubMedGoogle Scholar
  56. Friebe A, Mullershausen F, Smolenski A, Walter U, Schultz G, Koesling D (1998) YC-1 potentiates nitric oxide- and carbon monoxide-induced cyclic GMP effects in human platelets. Mol Pharmacol 54:962–967PubMedGoogle Scholar
  57. Friebe A, Mergia E, Dangel O, Lange A, Koesling D (2007) Fatal gastrointestinal obstruction and hypertension in mice lacking nitric oxide-sensitive guanylyl cyclase. Proc Natl Acad Sci USA 104:7699–7704PubMedGoogle Scholar
  58. Frisch C, Dere E, Silva MA, Godecke A, Schrader J, Huston JP (2000) Superior water maze performance and increase in fear-related behavior in the endothelial nitric oxide synthase- deficient mouse together with monoamine changes in cerebellum and ventral striatum. J Neu- rosci 20:6694–6700Google Scholar
  59. Fujiwara M, Sengupta P, McIntire SL (2002) Regulation of body size and behavioral state of C. elegans by sensory perception and the EGL-4 cGMP-dependent protein kinase. Neuron 36:1091–1102PubMedGoogle Scholar
  60. Fukazawa Y, Saitoh Y, Ozawa F, Ohta Y, Mizuno K, Inokuchi K (2003) Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo. Neuron 38:447–460PubMedGoogle Scholar
  61. Garthwaite J, Boulton CL (1995) Nitric oxide signaling in the central nervous system. Annu Rev Physiol 57:683–706PubMedGoogle Scholar
  62. Garthwaite G, Bartus K, Malcolm D, Goodwin D, Kollb-Sielecka M, Dooldeniya C, Garthwaite J (2006) Signaling from blood vessels to CNS axons through nitric oxide. J Neurosci 26:7730–7740PubMedGoogle Scholar
  63. Geiselhoringer A, Gaisa M, Hofmann F, Schlossmann J (2004) Distribution of IRAG and cGKI- isoforms in murine tissues. FEBS Lett 575:19–22PubMedGoogle Scholar
  64. Gibb BJ, Garthwaite J (2001) Subunits of the nitric oxide receptor, soluble guanylyl cyclase, expressed in rat brain. Eur J Neurosci 13:539–544PubMedGoogle Scholar
  65. Gonzalez Bosc LV, Wilkerson MK, Bradley KN, Eckman DM, Hill-Eubanks DC, Nelson MT (2004) Intraluminal pressure is a stimulus for NFATc3 nuclear accumulation:role of calcium, endothelium-derived nitric oxide, and cGMP-dependent protein kinase. J Biol Chem 279:10702–10709PubMedGoogle Scholar
  66. Graef IA, Mermelstein PG, Stankunas K, Neilson JR, Deisseroth K, Tsien RW, Crabtree GR (1999) L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons. Nature 401:703–708PubMedGoogle Scholar
  67. Graef IA, Wang F, Charron F, Chen L, Neilson J, Tessier-Lavigne M, Crabtree GR (2003) Neu- rotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons. Cell 113:657–670PubMedGoogle Scholar
  68. Groth RD, Mermelstein PG (2003) Brain-derived neurotrophic factor activation of NFAT (nuclear factor of activated T-cells)-dependent transcription:a role for the transcription factor NFATc4 in neurotrophin-mediated gene expression. J Neurosci 23:8125–8134PubMedGoogle Scholar
  69. Groth RD, Coicou LG, Mermelstein PG, Seybold VS (2007) Neurotrophin activation of NFAT- dependent transcription contributes to the regulation of pro-nociceptive genes. J Neurochem 102:1162–1174PubMedGoogle Scholar
  70. Guix FX, Uribesalgo I, Coma M, Munoz FJ (2005) The physiology and pathophysiology of nitric oxide in the brain. Prog Neurobiol 76:126–152PubMedGoogle Scholar
  71. Haghikia A, Mergia E, Friebe A, Eysel UT, Koesling D, Mittmann T (2007) Long-term potentiation in the visual cortex requires both nitric oxide receptor guanylyl cyclases. J Neurosci 27:818–823PubMedGoogle Scholar
  72. Haley JE, Wilcox GL, Chapman PF (1992) The role of nitric oxide in hippocampal long-term potentiation. Neuron 8:211–216PubMedGoogle Scholar
  73. Hall KU, Collins SP, Gamm DM, Massa E, DePaoli-Roach AA, Uhler MD (1999) Phosphorylation-dependent inhibition of protein phosphatase-1 by G-substrate. A Purkinje cell substrate of the cyclic GMP-dependent protein kinase. J Biol Chem 274:3485–3495PubMedGoogle Scholar
  74. Han J, Mark MD, Li X, Xie M, Waka S, Rettig J, Herlitze S (2006) RGS2 determines short-term synaptic plasticity in hippocampal neurons by regulating Gi/o-mediated inhibition of presynaptic Ca2+ channels. Neuron 51:575–586PubMedGoogle Scholar
  75. Hartell NA (1994) cGMP acts within cerebellar Purkinje cells to produce long term depression via mechanisms involving PKC and PKG. Neuroreport 5:833–836PubMedCrossRefGoogle Scholar
  76. Haul S, Godecke A, Schrader J, Haas HL, Luhmann HJ (1999) Impairment of neocortical long- term potentiation in mice deficient of endothelial nitric oxide synthase. J Neurophysiol 81:494–497PubMedGoogle Scholar
  77. Hauser W, Knobeloch KP, Eigenthaler M, Gambaryan S, Krenn V, Geiger J, Glazova M, Rohde E, Horak I, Walter U, Zimmer M (1999) Megakaryocyte hyperplasia and enhanced agonist- induced platelet activation in vasodilator-stimulated phosphoprotein knockout mice. Proc Natl Acad Sci USA 96:8120–8125PubMedGoogle Scholar
  78. Hawkins RD, Son H, Arancio O (1998) Nitric oxide as a retrograde messenger during long-term potentiation in hippocampus. Prog Brain Res 118:155–172PubMedGoogle Scholar
  79. Hebb DO (1949) The organisation of behavior. A neurophsychological theory. Wiley, New YorkGoogle Scholar
  80. Henniger MS, Spanagel R, Wigger A, Landgraf R, Holter SM (2002) Alcohol self-administration in two rat lines selectively bred for extremes in anxiety-related behavior. Neuropsychopharma- cology 26:729–736Google Scholar
  81. Herman JP, Langub MC, Jr, Watson RE, Jr (1993) Localization of C-type natriuretic peptide mRNA in rat hypothalamus. Endocrinology 133:1903–1906PubMedGoogle Scholar
  82. Hinds HL, Goussakov I, Nakazawa K, Tonegawa S, Bolshakov VY (2003) Essential function of alpha-calcium/calmodulin-dependent protein kinase II in neurotransmitter release at a gluta- matergic central synapse. Proc Natl Acad Sci USA 100:4275–4280PubMedGoogle Scholar
  83. Ho AM, Jain J, Rao A, Hogan PG (1994) Expression of the transcription factor NFATp in a neuronal cell line and in the murine nervous system. J Biol Chem 269:28181–28186PubMedGoogle Scholar
  84. Hofmann F, Sold G (1972) A protein kinase activity from rat cerebellum stimulated by guanosine-3′:5′-monophosphate. Biochem Biophys Res Commun 49:1100–1107PubMedGoogle Scholar
  85. Hofmann F, Biel M, Feil R, Kleppisch T (2004) Mouse models of NO/natriuretic peptide/cGMP kinase signaling. In:Hein L, Offermanns S (eds) Handbook of Experimental Pharmacology, Vol. 159. Springer, Heidelberg, pp 95–130Google Scholar
  86. Hofmann F, Biel M, Kaupp UB (2005) International union of pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. Pharmacol Rev 57:455–462PubMedGoogle Scholar
  87. Hofmann F, Feil R, Kleppisch T, Schlossmann J (2006) Function of cGMP-dependent protein kinases as revealed by gene deletion. Physiol Rev 86:1–23PubMedGoogle Scholar
  88. Hollinger S, Hepler JR (2002) Cellular regulation of RGS proteins:modulators and integrators of G protein signaling. Pharmacol Rev 54:527–559PubMedGoogle Scholar
  89. Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108PubMedGoogle Scholar
  90. Hotchkiss AK, Pyter LM, Gatien ML, Wen JC, Milman HA, Nelson RJ (2005) Aggressive behavior increases after termination of chronic sildenafil treatment in mice. Physiol Behav 83:683–688PubMedGoogle Scholar
  91. Huang EP (1997) Synaptic plasticity:a role for nitric oxide in LTP. Curr Biol 7:R141–R143PubMedGoogle Scholar
  92. Huang YY, Kandel ER (1998) Postsynaptic induction and PKA-dependent expression of LTP in the lateral amygdala. Neuron 21:169–178PubMedGoogle Scholar
  93. Ingi T, Krumins AM, Chidiac P, Brothers GM, Chung S, Snow BE, Barnes CA, Lanahan AA, Siderovski DP, Ross EM, Gilman AG, Worley PF (1998) Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity. J Neurosci 18:7178–7188PubMedGoogle Scholar
  94. Ito M (2001) Cerebellar long-term depression:characterization, signal transduction, and functional roles. Physiol Rev 81:1143–1195PubMedGoogle Scholar
  95. Ito M (2002) Historical review of the significance of the cerebellum and the role of Purkinje cells in motor learning. Ann N Y Acad Sci 978:273–288PubMedGoogle Scholar
  96. Josselyn SA, Nguyen PV (2005) CREB, synapses and memory disorders:past progress and future challenges. Curr Drug Targets CNS Neurol Disord 4:481–497PubMedGoogle Scholar
  97. Josselyn SA, Shi C, Carlezon WA, Jr, Neve RL, Nestler EJ, Davis M (2001) Long-term memory is facilitated by cAMP response element-binding protein overexpression in the amygdala. J Neurosci 21:2404–2412PubMedGoogle Scholar
  98. Josselyn SA, Kida S, Silva AJ (2004) Inducible repression of CREB function disrupts amygdala- dependent memory. Neurobiol Learn Mem 82:159–163PubMedGoogle Scholar
  99. Jouvert P, Revel MO, Lazaris A, Aunis D, Langley K, Zwiller J (2004) Activation of the cGMP pathway in dopaminergic structures reduces cocaine-induced EGR-1 expression and locomotor activity. J Neurosci 24:10716–10725PubMedGoogle Scholar
  100. Katoh A, Kitazawa H, Itohara S, Nagao S (2000) Inhibition of nitric oxide synthesis and gene knockout of neuronal nitric oxide synthase impaired adaptation of mouse optokinetic response eye movements. Learn Mem 7:220–226PubMedGoogle Scholar
  101. Kemp-Harper B, Feil R (2008) Meeting report:cGMP matters. Sci Signal 1:pe12PubMedGoogle Scholar
  102. Kingston PA, Zufall F, Barnstable CJ (1996) Rat hippocampal neurons express genes for both rod retinal and olfactory cyclic nucleotide-gated channels:novel targets for cAMP/cGMP function. Proc Natl Acad Sci USA 93:10440–10445PubMedGoogle Scholar
  103. Kleppisch T, Pfeifer A, Klatt P, Ruth P, Montkowski A, Fassler R, Hofmann F (1999) Long-term potentiation in the hippocampal CA1 region of mice lacking cGMP-dependent kinases is normal and susceptible to inhibition of nitric oxide synthase. J Neurosci 19:48–55PubMedGoogle Scholar
  104. Kleppisch T, Wolfsgruber W, Feil S, Allmann R, Wotjak CT, Goebbels S, Nave KA, Hofmann F, Feil R (2003) Hippocampal cGMP-dependent protein kinase I supports an age- and protein synthesis-dependent component of long-term potentiation but is not essential for spatial reference and contextual memory. J Neurosci 23:6005–6012PubMedGoogle Scholar
  105. Koesling D, Mergia E, Taqatqeh F, Mittmann T, Becker A, Hoellt V, Grecksch G (2007) Functional roles of isoforms of NO-sensitive guanylyl cyclase. BMC Pharmacology 7:S44Google Scholar
  106. Komatsu Y, Nakao K, Suga S, Ogawa Y, Mukoyama M, Arai H, Shirakami G, Hosoda K, Nakagawa O, Hama N, et al. (1991) C-type natriuretic peptide (CNP) in rats and humans. Endocrinology 129:1104–1106PubMedCrossRefGoogle Scholar
  107. Kotera J, Yanaka N, Fujishige K, Imai Y, Akatsuka H, Ishizuka T, Kawashima K, Omori K (1997) Expression of rat cGMP-binding cGMP-specific phosphodiesterase mRNA in Purkinje cell layers during postnatal neuronal development. Eur J Biochem 249:434–442PubMedGoogle Scholar
  108. Kotera J, Fujishige K, Omori K (2000) Immunohistochemical localization of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in rat tissues. J Histochem Cytochem 48:685–693PubMedGoogle Scholar
  109. Kuhn M (2003) Structure, regulation, and function of mammalian membrane guanylyl cyclase receptors, with a focus on guanylyl cyclase-A. Circ Res 93:700–709PubMedGoogle Scholar
  110. Labouebe G, Lomazzi M, Cruz HG, Creton C, Lujan R, Li M, Yanagawa Y, Obata K, Watanabe M, Wickman K, Boyer SB, Slesinger PA, Luscher C (2007) RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nat Neurosci 10:1559–1568PubMedGoogle Scholar
  111. Larkman AU, Jack JJ (1995) Synaptic plasticity: hippocampal LTP. Curr Opin Neurobiol 5: 324–334PubMedGoogle Scholar
  112. Lein ES, Hawrylycz MJ, et al (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168–176PubMedGoogle Scholar
  113. L'Etoile ND, Coburn CM, Eastham J, Kistler A, Gallegos G, Bargmann CI (2002) The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory adaptation inC. elegans. Neuron 36:1079–1089PubMedGoogle Scholar
  114. Lev-Ram V, Makings LR, Keitz PF, Kao JP, Tsien RY (1995) Long-term depression in cerebellar Purkinje neurons results from coincidence of nitric oxide and depolarization-induced Ca2+transients. Neuron 15:407–415PubMedGoogle Scholar
  115. Lev-Ram V, Jiang T, Wood J, Lawrence DS, Tsien RY (1997a) Synergies and coincidence requirements between NO, cGMP, and Ca2+in the induction of cerebellar long-term depression. Neuron 18:1025–1038Google Scholar
  116. Lev-Ram V, Nebyelul Z, Ellisman MH, Huang PL, Tsien RY (1997b) Absence of cerebellar long-term depression in mice lacking neuronal nitric oxide synthase. Learn Mem 4:169–177Google Scholar
  117. Lewin MR, Walters ET (1999) Cyclic GMP pathway is critical for inducing long-term sensitization of nociceptive sensory neurons. Nat Neurosci 2:18–23PubMedGoogle Scholar
  118. Li S, Doss JC, Hardee EJ, Quock RM (2005) Involvement of cyclic GMP-dependent protein kinase in nitrous oxide-induced anxiolytic-like behavior in the mouse light/dark exploration test. Brain Res 1038:113–117PubMedGoogle Scholar
  119. Lisman J (2003) Actin's actions in LTP-induced synapse growth. Neuron 38:361–362Google Scholar
  120. Lisman J, Raghavachari S (2006) A unified model of the presynaptic and postsynaptic changes during LTP at CA1 synapses. Sci STKE 2006(356):re11Google Scholar
  121. Lisman J, Schulman H, Cline H (2002) The molecular basis of CaMKII function in synaptic and behavioural memory. Nat Rev Neurosci 3:175–190PubMedGoogle Scholar
  122. Liu S, Ninan I, Antonova I, Battaglia F, Trinchese F, Narasanna A, Kolodilov N, Dauer W, Hawkins RD, Arancio O (2004) Alpha-synuclein produces a long-lasting increase in neurotransmitter release. Embo J 23:4506–4516PubMedGoogle Scholar
  123. Lohmann SM, Walter U, Miller PE, Greengard P, De Camilli P (1981) Immunohistochemical localization of cyclic GMP-dependent protein kinase in mammalian brain. Proc Natl Acad Sci USA 78:653–657PubMedGoogle Scholar
  124. Lonze BE, Ginty DD (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35:605–623PubMedGoogle Scholar
  125. Lu YF, Hawkins RD (2002) Ryanodine receptors contribute to cGMP-induced late-phase LTP and CREB phosphorylation in the hippocampus. J Neurophysiol 88:1270–1278PubMedGoogle Scholar
  126. Lu YF, Kandel ER, Hawkins RD (1999) Nitric oxide signaling contributes to late-phase LTP and CREB phosphorylation in the hippocampus. J Neurosci 19:10250–10261PubMedGoogle Scholar
  127. Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44:5–21PubMedGoogle Scholar
  128. Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103–126PubMedGoogle Scholar
  129. Man HY, Lin JW, Ju WH, Ahmadian G, Liu L, Becker LE, Sheng M, Wang YT (2000) Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internaliza-tion. Neuron 25:649–662PubMedGoogle Scholar
  130. Manahan-Vaughan D, Braunewell KH (1999) Novelty acquisition is associated with induction of hippocampal long-term depression. Proc Natl Acad Sci USA 96:8739–8744PubMedGoogle Scholar
  131. Maren S, Quirk GJ (2004) Neuronal signalling of fear memory. Nat Rev Neurosci 5:844–852PubMedGoogle Scholar
  132. Martin TF (2001) PI(4,5)P(2) regulation of surface membrane traffic. Curr Opin Cell Biol 13: 493–499PubMedGoogle Scholar
  133. Mauk MD, Garcia KS, Medina JF, Steele PM (1998) Does cerebellar LTD mediate motor learning? Toward a resolution without a smoking gun. Neuron 20:359–362PubMedGoogle Scholar
  134. McKernan MG, Shinnick-Gallagher P (1997) Fear conditioning induces a lasting potentiation of synaptic currents in vitro. Nature 390:607–611PubMedGoogle Scholar
  135. Menniti FS, Faraci WS, Schmidt CJ (2006) Phosphodiesterases in the CNS: targets for drug development. Nat Rev Drug Discov 5:660–670PubMedGoogle Scholar
  136. Mergia E, Russwurm M, Zoidl G, Koesling D (2003) Major occurrence of the new alpha2beta1 isoform of NO-sensitive guanylyl cyclase in brain. Cell Signal 15:189–195PubMedGoogle Scholar
  137. Mergia E, Friebe A, Dangel O, Russwurm M, Koesling D (2006) Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system. J Clin Invest 116:1731–1737PubMedGoogle Scholar
  138. Mery F, Belay AT, So AK, Sokolowski MB, Kawecki TJ (2007) Natural polymorphism affecting learning and memory in Drosophila. Proc Natl Acad Sci USA 104:13051–13055PubMedGoogle Scholar
  139. Meyer-Lindenberg A, Straub RE, Lipska BK, Verchinski BA, Goldberg T, Callicott JH, Egan MF, Huffaker SS, Mattay VS, Kolachana B, Kleinman JE, Weinberger DR (2007) Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition. J Clin Invest 117:672–682PubMedGoogle Scholar
  140. Micheva KD, Holz RW, Smith SJ (2001) Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronal activity. J Cell Biol 154:355–368PubMedGoogle Scholar
  141. Micheva KD, Buchanan J, Holz RW, Smith SJ (2003) Retrograde regulation of synaptic vesicle endocytosis and recycling. Nat Neurosci 6:925–932PubMedGoogle Scholar
  142. Milman HA, Arnold SB (2002) Neurologic, psychological, and aggressive disturbances with silde-nafil. Ann Pharmacother 36:1129–1134PubMedGoogle Scholar
  143. Milner B (2003) Visual recognition and recall after right temporal-lobe excision in man. Epilepsy Behav 4:799–812PubMedGoogle Scholar
  144. Ninan I, Arancio O (2004) Presynaptic CaMKII is necessary for synaptic plasticity in cultured hippocampal neurons. Neuron 42:129–141PubMedGoogle Scholar
  145. Nishi A, Watanabe Y, Higashi H, Tanaka M, Nairn AC, Greengard P (2005) Glutamate regulation of DARPP-32 phosphorylation in neostriatal neurons involves activation of multiple signaling cascades. Proc Natl Acad Sci USA 102:1199–1204PubMedGoogle Scholar
  146. Nolan MF, Malleret G, Dudman JT, Buhl DL, Santoro B, Gibbs E, Vronskaya S, Buzsaki G, Siegelbaum SA, Kandel ER, Morozov A (2004) A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons. Cell 119:719–732PubMedGoogle Scholar
  147. Nugent FS, Penick EC, Kauer JA (2007) Opioids block long-term potentiation of inhibitory synapses. Nature 446:1086–1090PubMedGoogle Scholar
  148. O'Dell TJ, Huang PL, Dawson TM, Dinerman JL, Snyder SH, Kandel ER, Fishman MC (1994) Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS. Science 265:542–546PubMedGoogle Scholar
  149. Oliveira-Dos-Santos AJ, Matsumoto G, Snow BE, Bai D, Houston FP, Whishaw IQ, Mariathasan S, Sasaki T, Wakeham A, Ohashi PS, Roder JC, Barnes CA, Siderovski DP, Penninger JM (2000) Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc Natl Acad Sci USA 97:12272–12277PubMedGoogle Scholar
  150. Osborne KA, Robichon A, Burgess E, Butland S, Shaw RA, Coulthard A, Pereira HS, Greenspan RJ, Sokolowski MB (1997) Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila. Science 277:834–836PubMedGoogle Scholar
  151. Osborne SL, Meunier FA, Schiavo G (2001) Phosphoinositides as key regulators of synaptic function. Neuron 32:9–12PubMedGoogle Scholar
  152. Oster H, Werner C, Magnone MC, Mayser H, Feil R, Seeliger MW, Hofmann F, Albrecht U (2003) cGMP-dependent protein kinase II modulates mPer1 and mPer2 gene induction and influences phase shifts of the circadian clock. Curr Biol 13:725–733PubMedGoogle Scholar
  153. Parent A, Schrader K, Munger SD, Reed RR, Linden DJ, Ronnett GV (1998) Synaptic transmission and hippocampal long-term potentiation in olfactory cyclic nucleotide-gated channel type 1 null mouse. J Neurophysiol 79:3295–3301PubMedGoogle Scholar
  154. Paul C, Weinmeister P, Feil R, Hofmann F, Kleppisch T (2007) cGMP-dependent kinase I supports formation of associative fear memory and long-term potentiation in the lateral amygdala. BMC Pharmacol 7:P46Google Scholar
  155. Pedram A, Razandi M, Kehrl J, Levin ER (2000) Natriuretic peptides inhibit G protein activation. Mediation through cross-talk between cyclic GMP-dependent protein kinase and regulators of G protein-signaling proteins. J Biol Chem 275:7365–7372PubMedGoogle Scholar
  156. Pfeifer A, Aszodi A, Seidler U, Ruth P, Hofmann F, Fassler R (1996) Intestinal secretory defects and dwarfism in mice lacking cGMP-dependent protein kinase II. Science 274:2082–2086PubMedGoogle Scholar
  157. Pfeifer A, Klatt P, Massberg S, Ny L, Sausbier M, Hirneiss C, Wang GX, Korth M, Aszodi A, Andersson KE, Krombach F, Mayerhofer A, Ruth P, Fassler R, Hofmann F (1998) Defective smooth muscle regulation in cGMP kinase I-deficient mice. Embo J 17:3045–3051PubMedGoogle Scholar
  158. Pilz RB, Casteel DE (2003) Regulation of gene expression by cyclic GMP. Circ Res 93:1034–1046PubMedGoogle Scholar
  159. Plant K, Pelkey KA, Bortolotto ZA, Morita D, Terashima A, McBain CJ, Collingridge GL, Isaac JT (2006) Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation. Nat Neurosci 9:602–604PubMedGoogle Scholar
  160. Prasad HC, Zhu CB, McCauley JL, Samuvel DJ, Ramamoorthy S, Shelton RC, Hewlett WA, Sutcliffe JS, Blakely RD (2005) Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase. Proc Natl Acad Sci USA 102:11545–11550PubMedGoogle Scholar
  161. Prickaerts J, van Staveren WC, Sik A, Markerink-van Ittersum M, Niewohner U, van der Staay FJ, Blokland A, de Vente J (2002) Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat. Neuroscience 113:351–361PubMedGoogle Scholar
  162. Prickaerts J, Sik A, van Staveren WC, Koopmans G, Steinbusch HW, van der Staay FJ, de Vente J, Blokland A (2004) Phosphodiesterase type 5 inhibition improves early memory consolidation of object information. Neurochem Int 45:915–928PubMedGoogle Scholar
  163. Puzzo D, Vitolo O, Trinchese F, Jacob JP, Palmeri A, Arancio O (2005) Amyloid-beta peptide inhibits activation of the nitric oxide/cGMP/cAMP-responsive element-binding protein pathway during hippocampal synaptic plasticity. J Neurosci 25:6887–6897PubMedGoogle Scholar
  164. Raizen DM, Zimmerman JE, Maycock MH, Ta UD, You YJ, Sundaram MV, Pack AI (2008) Lethargus is aCaenorhabditis elegans sleep-like state. Nature 451:569–572PubMedGoogle Scholar
  165. Rapoport M, van Reekum R, Mayberg H (2000) The role of the cerebellum in cognition and behavior: a selective review. J Neuropsychiatry Clin Neurosci 12:193–198PubMedGoogle Scholar
  166. Raymond JL, Lisberger SG, Mauk MD (1996) The cerebellum: a neuronal learning machine? Science 272:1126–1131PubMedGoogle Scholar
  167. Reinhard M, Jarchau T, Walter U (2001) Actin-based motility: stop and go with Ena/VASP proteins. Trends Biochem Sci 26:243–249PubMedGoogle Scholar
  168. Repaske DR, Corbin JG, Conti M, Goy MF (1993) A cyclic GMP-stimulated cyclic nucleotide phosphodiesterase gene is highly expressed in the limbic system of the rat brain. Neuroscience 56:673–686PubMedGoogle Scholar
  169. Revermann M, Maronde E, Ruth P, Korf HW (2002) Protein kinase G I immunoreaction is colo-calized with arginine-vasopressin immunoreaction in the rat suprachiasmatic nucleus. Neurosci Lett 334:119–122PubMedGoogle Scholar
  170. Reyes M, Stanton PK (1996) Induction of hippocampal long-term depression requires release of Ca2+from separate presynaptic and postsynaptic intracellular stores. J Neurosci 16:5951–5960PubMedGoogle Scholar
  171. Reyes-Harde M, Empson R, Potter BV, Galione A, Stanton PK (1999a) Evidence of a role for cyclic ADP-ribose in long-term synaptic depression in hippocampus. Proc Natl Acad Sci USA 96:4061–4066Google Scholar
  172. Reyes-Harde M, Potter BV, Galione A, Stanton PK (1999b) Induction of hippocampal LTD requires nitric-oxide-stimulated PKG activity and Ca2+release from cyclic ADP-ribose-sensitive stores. J Neurophysiol 82:1569–1576Google Scholar
  173. Rieke F, Schwartz EA (1994) A cGMP-gated current can control exocytosis at cone synapses. Neuron 13:863–873PubMedGoogle Scholar
  174. Rogan MT, Staubli UV, LeDoux JE (1997) Fear conditioning induces associative long-term poten-tiation in the amygdala. Nature 390:604–607PubMedGoogle Scholar
  175. Rumpel S, LeDoux J, Zador A, Malinow R (2005) Postsynaptic receptor trafficking underlying a form of associative learning. Science 308:83–88PubMedGoogle Scholar
  176. Russwurm M, Wittau N, Koesling D (2001) Guanylyl cyclase/PSD-95 interaction: targeting of the nitric oxide-sensitive alpha2beta1 guanylyl cyclase to synaptic membranes. J Biol Chem 276:44647–44652PubMedGoogle Scholar
  177. Sabatini MJ, Ebert P, Lewis DA, Levitt P, Cameron JL, Mirnics K (2007) Amygdala gene expression correlates of social behavior in monkeys experiencing maternal separation. J Neurosci 27:3295–3304PubMedGoogle Scholar
  178. Sano H, Nagai Y, Miyakawa T, Shigemoto R, Yokoi M (2008) Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2. J Neurochem 105(2):546–556PubMedGoogle Scholar
  179. Sato T, Suzuki E, Yokoyama M, Watanabe S, Miyaoka H (2006) Auditory fear conditioning and conditioned stress raise NO(3) level in the amygdala. Neuropsychobiology 53:142–147PubMedGoogle Scholar
  180. Savchenko A, Barnes S, Kramer RH (1997) Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide. Nature 390:694–698PubMedGoogle Scholar
  181. Schafe GE, Bauer EP, Rosis S, Farb CR, Rodrigues SM, LeDoux JE (2005) Memory consolidation of Pavlovian fear conditioning requires nitric oxide signaling in the lateral amygdala. Eur J Neurosci 22:201–211PubMedGoogle Scholar
  182. Schmidt CJ, Chapin DS, Cianfrogna J, Corman ML, Hajos M, Harms JF, Hoffman WE, Lebel LA, McCarthy SA, Nelson FR, Proulx-Lafrance C, Majchrzak MJ, Ramirez AD, Schmidt K, Seymour PA, Siuciak JA, Tingley Iii FD, Williams RD, Verhoest PR, Menniti FS (2008) Pre-clinical characterization of selective PDE10A inhibitors: a new therapeutic approach to the treatment of schizophrenia. J Pharmacol Exp Ther 325(2):681–690PubMedGoogle Scholar
  183. Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neu-rochem 20:11–21Google Scholar
  184. Serulle Y, Zhang S, Ninan I, Puzzo D, McCarthy M, Khatri L, Arancio O, Ziff EB (2007) A GluR1-cGKII interaction regulates AMPA receptor trafficking. Neuron 56:670–688PubMedGoogle Scholar
  185. Shin JH, Linden DJ (2005) An NMDA receptor/nitric oxide cascade is involved in cerebellar LTD but is not localized to the parallel fiber terminal. J Neurophysiol 94:4281–4289PubMedGoogle Scholar
  186. Sigurdsson T, Doyere V, Cain CK, LeDoux JE (2007) Long-term potentiation in the amygdala: a cellular mechanism of fear learning and memory. Neuropharmacology 52:215–227PubMedGoogle Scholar
  187. Siuciak JA, McCarthy SA, Chapin DS, Martin AN, Harms JF, Schmidt CJ (2008) Behavioral characterization of mice deficient in the phosphodiesterase-10A (PDE10A) enzyme on a C57/Bl6N congenic background. Neuropharmacology 54:417–427PubMedGoogle Scholar
  188. Sokolowski M (2007) cGMP kinase and food-related behaviours. BMC Pharmacol 7:S46Google Scholar
  189. 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 87:1015–1023PubMedGoogle Scholar
  190. Starke K (1981) Presynaptic receptors. Annu Rev Pharmacol Toxicol 21:7–30PubMedGoogle Scholar
  191. Straub RE, Lehner T, Luo Y, Loth JE, Shao W, Sharpe L, Alexander JR, Das K, Simon R, Fieve RR, et al (1994) A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3. Nat Genet 8:291–296PubMedGoogle Scholar
  192. Strijbos PJ, Pratt GD, Khan S, Charles IG, Garthwaite J (1999) Molecular characterization and in situ localization of a full-length cyclic nucleotide-gated channel in rat brain. Eur J Neurosci 11:4463–4467PubMedGoogle Scholar
  193. Sudoh T, Minamino N, Kangawa K, Matsuo H (1988) Brain natriuretic peptide-32: N-terminal six amino acid extended form of brain natriuretic peptide identified in porcine brain. Biochem Biophys Res Commun 155:726–732PubMedGoogle Scholar
  194. Sudoh T, Minamino N, Kangawa K, Matsuo H (1990) C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Com-mun 168:863–870Google Scholar
  195. Sun X, Kaltenbronn KM, Steinberg TH, Blumer KJ (2005) RGS2 is a mediator of nitric oxide action on blood pressure and vasoconstrictor signaling. Mol Pharmacol 67:631–639PubMedGoogle Scholar
  196. Svenningsson P, Nishi A, Fisone G, Girault JA, Nairn AC, Greengard P (2004) DARPP-32: an integrator of neurotransmission. Annu Rev Pharmacol Toxicol 44:269–296PubMedGoogle Scholar
  197. Szabadits E, Cserep C, Ludanyi A, Katona I, Gracia-Llanes J, Freund TF, Nyiri G (2007) Hip-pocampal GABAergic synapses possess the molecular machinery for retrograde nitric oxide signaling. J Neurosci 27:8101–8111PubMedGoogle Scholar
  198. Tang KM, Wang GR, Lu P, Karas RH, Aronovitz M, Heximer SP, Kaltenbronn KM, Blumer KJ, Siderovski DP, Zhu Y, Mendelsohn ME (2003) Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med 9:1506–1512PubMedGoogle Scholar
  199. Tsay D, Dudman JT, Siegelbaum SA (2007) HCN1 channels constrain synaptically evoked Ca2+spikes in distal dendrites of CA1 pyramidal neurons. Neuron 56:1076–1089PubMedGoogle Scholar
  200. Tsou K, Snyder GL, Greengard P (1993) Nitric oxide/cGMP pathway stimulates phosphorylation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, in the substantia nigra. Proc Natl Acad Sci USA 90:3462–3465PubMedGoogle Scholar
  201. Tsvetkov E, Carlezon WA, Benes FM, Kandel ER, Bolshakov VY (2002) Fear conditioning occludes LTP-induced presynaptic enhancement of synaptic transmission in the cortical pathway to the lateral amygdala. Neuron 34:289–300PubMedGoogle Scholar
  202. Uhl GR, Liu QR, Drgon T, Johnson C, Walther D, Rose JE (2007) Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs. BMC Genet 8:10PubMedGoogle Scholar
  203. van Staveren WC, Markerink-van Ittersum M, Steinbusch HW, Behrends S, de Vente J (2005) Localization and characterization of cGMP-immunoreactive structures in rat brain slices after NO-dependent and NO-independent stimulation of soluble guanylyl cyclase. Brain Res 1036:77–89PubMedGoogle Scholar
  204. Volke V, Wegener G, Vasar E (2003) Augmentation of the NO-cGMP cascade induces anxiogenic-like effect in mice. J Physiol Pharmacol 54:653–660PubMedGoogle Scholar
  205. Wang YT, Linden DJ (2000) Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron 25:635–647PubMedGoogle Scholar
  206. Wang HG, Lu FM, Jin I, Udo H, Kandel ER, de Vente J, Walter U, Lohmann SM, Hawkins RD, Antonova I (2005) Presynaptic and postsynaptic roles of NO, cGK, and RhoA in long-lasting potentiation and aggregation of synaptic proteins. Neuron 45:389–403PubMedGoogle Scholar
  207. Watanabe Y, Saito H, Abe K (1995) Nitric oxide is involved in long-term potentiation in the medial but not lateral amygdala neuron synapses in vitro. Brain Res 688:233–236PubMedGoogle Scholar
  208. Weber S, Bernhard D, Lukowski R, Weinmeister P, Worner R, Wegener JW, Valtcheva N, Feil S, Schlossmann J, Hofmann F, Feil R (2007) Rescue of cGMP kinase I knockout mice by smooth muscle specific expression of either isozyme. Circ Res 101(11):1096–1103PubMedGoogle Scholar
  209. Wegener JW, Nawrath H, Wolfsgruber W, Kuhbandner S, Werner C, Hofmann F, Feil R (2002) cGMP-dependent protein kinase I mediates the negative inotropic effect of cGMP in the murine myocardium. Circ Res 90:18–20PubMedGoogle Scholar
  210. Welsh JP, Yamaguchi H, Zeng XH, Kojo M, Nakada Y, Takagi A, Sugimori M, Llinas RR (2005) Normal motor learning during pharmacological prevention of Purkinje cell long-term depression. Proc Natl Acad Sci USA 102:17166–17171PubMedGoogle Scholar
  211. Werner C, Raivich G, Cowen M, Strekalova T, Sillaber I, Buters JT, Spanagel R, Hofmann F (2004) Importance of NO/cGMP signalling via cGMP-dependent protein kinase II for controlling emotionality and neurobehavioural effects of alcohol. Eur J Neurosci 20:3498–3506PubMedGoogle Scholar
  212. Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006) Learning induces long-term potentiation in the hippocampus. Science 313:1093–1097PubMedGoogle Scholar
  213. Wilson RI, Godecke A, Brown RE, Schrader J, Haas HL (1999) Mice deficient in endothelial nitric oxide synthase exhibit a selective deficit in hippocampal long-term potentiation. Neuroscience 90:1157–1165PubMedGoogle Scholar
  214. Wisden W, Seeburg PH (1993) Mammalian ionotropic glutamate receptors. Curr Opin Neurobiol 3:291–298PubMedGoogle Scholar
  215. Wong ML, Whelan F, Deloukas P, Whittaker P, Delgado M, Cantor RM, McCann SM, Licinio J (2006) Phosphodiesterase genes are associated with susceptibility to major depression and antidepressant treatment response. Proc Natl Acad Sci USA 103:15124–15129PubMedGoogle Scholar
  216. Xia C, Bao Z, Yue C, Sanborn BM, Liu M (2001) Phosphorylation and regulation of G-protein-activated phospholipase C-beta 3 by cGMP-dependent protein kinases. J Biol Chem 276:19770–19777PubMedGoogle Scholar
  217. Zhang YW, Gesmonde J, Ramamoorthy S, Rudnick G (2007) Serotonin transporter phosphory-lation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder. J Neurosci 27:10878–10886PubMedGoogle Scholar
  218. Zhu CB, Hewlett WA, Feoktistov I, Biaggioni I, Blakely RD (2004) Adenosine receptor, protein kinase G, and p38 mitogen-activated protein kinase-dependent up-regulation of serotonin transporters involves both transporter trafficking and activation. Mol Pharmacol 65:1462–1474PubMedGoogle Scholar
  219. Zhuo M, Hu Y, Schultz C, Kandel ER, Hawkins RD (1994) Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation. Nature 368:635–639PubMedGoogle Scholar
  220. Zufall F, Shepherd GM, Barnstable CJ (1997) Cyclic nucleotide gated channels as regulators of CNS development and plasticity. Curr Opin Neurobiol 7:404–412PubMedGoogle Scholar

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© Springer 2009

Authors and Affiliations

  1. 1.Institut für Pharmakologie und ToxikologieTechnische Universität MünchenMünchenGermany
  2. 2.Interfakultäres Institut für BiochemieUniversität TübingenTübingenGermany

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