Glycine transporter-1 inhibition promotes striatal axon sprouting via NMDA receptors in dopamine neurons

Journal of Neuroscience

Volumn 33, Issue 42, 2013, Pages 16778-16789

  Schmitz, Yvonne ^a   Castagna, Candace ^a   Mrejeru, Ana ^a   Lizardi Ortiz, José E ^a   Klein, Zoe ^a   Lindsley, Craig W ^b   Sulzer, David ^a  

^a NewYork Presbyterian Hospital   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 4 CHLORO N (1 (4 PHENYL 1 (PROPYLSULFONYL)PIPERIDIN 4 YL)ETHYL)BENZAMIDE S 35; 6 NITRO 7 SULFAMOYLBENZO [F] QUINOXALINE 2, 3 DIONE; DOPAMINE; GLYCINE TRANSPORTER 1; N [3 (4 FLUOROPHENYL) 3 (4 PHENYLPHENOXY) PROPYL] SARCOSINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN DAMAGE; CONTROLLED STUDY; CYCLIC POTENTIOMETRY; DOPAMINERGIC NERVE CELL; ELECTROSTIMULATION; EXCITATORY POSTSYNAPTIC POTENTIAL; HEMISPHERIC DOMINANCE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IMMUNOHISTOLOGY; MALE; MOUSE; NERVE FIBER GROWTH; NERVE SPROUTING; NONHUMAN; PATCH CLAMP; PRIORITY JOURNAL; PROTEIN EXPRESSION; SENSORIMOTOR FUNCTION; SPIKE WAVE;

ANIMALS; AXONS; BEHAVIOR, ANIMAL; CORPUS STRIATUM; DOPAMINERGIC NEURONS; GLYCINE PLASMA MEMBRANE TRANSPORT PROTEINS; MESENCEPHALON; MICE; MOTOR SKILLS; OXIDOPAMINE; PARKINSON DISEASE, SECONDARY; RECEPTORS, N-METHYL-D-ASPARTATE; RECOVERY OF FUNCTION; SUBSTANTIA NIGRA;

EID: 84885460335     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.3041-12.2013     Document Type: Article

References (86)

1. Alberati D, Moreau JL, Lengyel J, Hauser N, Mory R, Borroni E, Pinard E, Knoflach F, Schlotterbeck G, Hainzl D, Wettstein JG (2012) Glycine reuptake inhibitor RG1678: a pharmacologic characterization of an investigational agent for the treatment of schizophrenia. Neuropharmacology 62:1152-1161. CrossRef Medline
2. Alsiö J, Nordenankar K, Arvidsson E, Birgner C, Mahmoudi S, Halbout B, Smith C, Fortin GM, Olson L, Descarries L, Trudeau LÉ, Kullander K, Lévesque D, Wallén-MackenzieA (2011) Enhanced sucrose and cocaine self-administration and cue-induced drug seeking after loss of VGLUT2 in midbrain dopamine neurons in mice. J Neurosci 31:12593-12603. CrossRef Medline
3. Bäckman CM, Malik N, Zhang Y, Shan L, Grinberg A, Hoffer BJ, Westphal H, Tomac AC (2006) Characterization of a mouse strain expressing Cre recombinase from the 3 untranslated region of the dopamine transporter locus. Genesis 44:383-390. CrossRef Medline
4. Berger AJ, Dieudonné S, Ascher P (1998) Glycine uptake governs glycine site occupancy atNMDAreceptors of excitatory synapses. J Neurophysiol 80:3336-3340. Medline
5. Bergeron R, Meyer TM, Coyle JT, Greene RW (1998) Modulation of N-methyl-D-aspartate receptor function by glycine transport. Proc Natl Acad Sci U S A 95:15730-15734. CrossRef Medline
6. Bérubé-Carrière N, Riad M, Dal Bo G, Lévesque D, Trudeau LE, Descarries L (2009) The dual dopamine-glutamate phenotype of growing mesencephalic neurons regresses in mature rat brain. J Comp Neurol 517:873-891. CrossRef Medline
7. Borroni E, Zhou Y, Ostrowitzki S, Alberati D, Kumar A, Hainzl D, Hartung T, Hilton J, Dannals RF, Wong DF (2013) Pre-clinical characterization of [(11)C]R05013853 as a novel radiotracer for imaging of the glycine transporter type 1 by positron emission tomography. Neuroimage 75:291-300. CrossRef Medline
8. Bouyer JJ, Park DH, Joh TH, Pickel VM (1984) Chemical and structural analysis of the relation between cortical inputs and tyrosine hydroxylasecontaining terminals in rat neostriatum. Brain Res 302:267-275. CrossRef Medline
9. Bridges TM, Williams R, Lindsley CW (2008) Design of potent GlyT1 inhibitors: in vitro and in vivo profiles. Curr Opin Mol Ther 10:591-601. Medline
10. Calabresi P, Di Filippo M, Ghiglieri V, Tambasco N, Picconi B (2010) Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap. Lancet Neurol 9:1106-1117. CrossRef Medline
11. Cheng HC, Ulane CM, Burke RE (2010) Clinical progression in Parkinson disease and the neurobiology of axons. Ann Neurol 67:715-725. CrossRef Medline
12. Christie JM, Jahr CE (2008) DendriticNMDAreceptors activate axonal calcium channels. Neuron 60:298-307. CrossRef Medline
13. Chuhma N, Zhang H, Masson J, Zhuang X, Sulzer D, Hen R, Rayport S (2004) Dopamine neurons mediate a fast excitatory signal via their glutamatergic synapses. J Neurosci 24:972-981. CrossRef Medline
14. Clements JD, Westbrook GL (1991) Activation kinetics reveal the number of glutamate and glycine binding sites on the N-methyl-D-aspartate receptor. Neuron 7:605-613. CrossRef Medline
15. Colonnese MT, Zhao JP, Constantine-Paton M (2005) NMDA receptor currents suppress synapse formation on sprouting axons in vivo. J Neurosci 25:1291-1303. CrossRef Medline
16. Constantine-Paton M, Cline HT (1998) LTP and activity-dependent synaptogenesis: the more alike they are, the more different they become. Curr Opin Neurobiol 8:139-148. CrossRef Medline
17. Corlew R, Wang Y, Ghermazien H, Erisir A, Philpot BD (2007) Developmental switch in the contribution of presynaptic and postsynapticNMDA receptors to long-term depression. J Neurosci 27:9835-9845. CrossRef Medline
18. Cubelos B, Giménez C, Zafra F (2005) Localization of the GLYT1 glycine transporter at glutamatergic synapses in the rat brain. Cereb Cortex 15: 448-459. CrossRef Medline Dal
19. Bo G, Bérubé-Carrière N, Mendez JA, Leo D, Riad M, Descarries L, Lévesque D, Trudeau LE (2008) Enhanced glutamatergic phenotype of mesencephalic dopamine neurons after neonatal 6-hydroxydopamine lesion. Neuroscience 156:59-70. CrossRef Medline
20. Decressac M, Ulusoy A, Mattsson B, Georgievska B, Romero-Ramos M, Kirik D, Björklund A (2011) GDNF fails to exert neuroprotection in a rat alpha-synuclein model of Parkinson's disease. Brain 134:2302-2311. CrossRef Medline
21. Desce JM, Godeheu G, Galli T, Artaud F, Chéramy A, Glowinski J (1992) L-glutamate-evoked release of dopamine from synaptosomes of the rat striatum: involvement of AMPA and N-methyl-D-aspartate receptors. Neuroscience 47:333-339. CrossRef Medline
22. Dowd E, Monville C, Torres EM, Dunnett SB (2005) The Corridor Task: a simple test of lateralised response selection sensitive to unilateral dopamine deafferentation and graft-derived dopamine replacement in the striatum. Brain Res Bull 68:24-30. CrossRef Medline
23. Dravid A, Jaton AL, Enz A, Frei P (1984) Spontaneous recovery from motor asymmetry in adult rats with 6-hydroxydopamine-induced partial lesions of the substantia nigra. Brain Res 311:361-365. CrossRef Medline
24. Eulenburg V, Armsen W, Betz H, Gomeza J (2005) Glycine transporters: essential regulators of neurotransmission. Trends Biochem Sci 30:325-333. CrossRef Medline
25. Eulenburg V, Retiounskaia M, Papadopoulos T, Gomeza J, Betz H (2010) Glial glycine transporter 1 function is essential for early postnatal survival but dispensable in adult mice. Glia 58:1066-1073. CrossRef Medline
26. Finkelstein DI, Stanic D, Parish CL, Tomas D, Dickson K, HorneMK (2000) Axonal sprouting following lesions of the rat substantia nigra. Neuroscience 97:99-112. CrossRef Medline
27. Franklin K, PaxinosG(1997) The mouse brain in stereotaxic coordinates. San Diego: Academic.
28. Gelfin E, Kaufman Y, Korn-Lubetzki I, Bloch B, Kremer I, Javitt DC, Heresco-Levy U (2012) D-serine adjuvant treatment alleviates behavioural and motor symptoms in Parkinson's disease. Int J Neuropsychopharmacol 15:543-549. Medline
29. Gracy KN, Pickel VM (1996) Ultrastructural immunocytochemical localization of the N-methyl-D-aspartate receptor and tyrosine hydroxylase in the shell of the rat nucleus accumbens. Brain Res 739:169-181. CrossRef Medline
30. Gray JA, Nicoll RA (2012) Thinking outside the synapse: glycine at extrasynaptic NMDA receptors. Cell 150:455-456. CrossRef Medline
31. Grealish S, Mattsson B, Draxler P, Björklund A (2010) Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease. Eur J Neurosci 31:2266-2278. CrossRef Medline
32. Hamill TG, Eng W, Jennings A, Lewis R, Thomas S, Wood S, Street L, Wisnoski D, Wolkenberg S, Lindsley C, Sanabria-Bohó rquez SM, Patel S, Riffel K, Ryan C, Cook J, Sur C, Burns HD, Hargreaves R (2011) The synthesis and preclinical evaluation in rhesus monkey of [(1)(8)F]MK-6577 and [(1)(1)C]CMPyPB glycine transporter 1 positron emission tomography radiotracers. Synapse 65:261-270. CrossRef Medline
33. Hansen JT, Sakai K, Greenamyre JT, Moran S (1995) Sprouting of dopaminergic fibers from spared mesencephalic dopamine neurons in the unilateral partial lesioned rat. Brain Res 670:197-204. CrossRef Medline
34. Herdon HJ, Roberts JC, Coulton S, PorterRA (2010) Pharmacological characterisation of the GlyT-1 glycine transporter using two novel radioligands. Neuropharmacology 59:558-565. CrossRef Medline
35. Heresco-Levy U, Shoham S, Javitt DC (2013) Glycine site agonists of the N-methyl-D-aspartate receptor and Parkinson's disease: a hypothesis. Mov Disord 28:419-424. CrossRef Medline
36. Herkert M, Röttger S, Becker CM (1998) The NMDA receptor subunit NR2B of neonatal rat brain: complex formation and enrichment in axonal growth cones. Eur J Neurosci 10:1553-1562. CrossRef Medline
37. Hnasko TS, Chuhma N, Zhang H, Goh GY, Sulzer D, Palmiter RD, Rayport S, Edwards RH (2010) Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. Neuron 65:643-656. CrossRef Medline
38. Javitt DC (2008) Glycine transport inhibitors and the treatment of schizophrenia. Biol Psychiatry 63:6-8. CrossRef Medline
39. Javitt DC, Balla A, Burch S, Suckow R, Xie S, Sershen H (2004) Reversal of phencyclidine-induced dopaminergic dysregulation by N-methyl-Daspartate receptor/glycine-site agonists. Neuropsychopharmacology 29: 300-307. CrossRef Medline
40. Jourdain P, Bergersen LH, Bhaukaurally K, Bezzi P, Santello M, Domercq M, Matute C, Tonello F, Gundersen V, Volterra A (2007) Glutamate exocytosis from astrocytes controls synaptic strength. Nat Neurosci 10:331-339. CrossRef Medline
41. Katz LC, Shatz CJ (1996) Synaptic activity and the construction of cortical circuits. Science 274:1133-1138. CrossRef Medline
42. Kirik D, Georgievska B, Björklund A (2004) Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nat Neurosci 7:105-110. CrossRef Medline
43. Krebs MO, Kemel ML, Gauchy C, Desban M, Glowinski J (1989) Glycine potentiates the NMDA-induced release of dopamine through a strychnine-insensitive site in the rat striatum. Eur J Pharmacol 166:567-570. CrossRef Medline
44. Larsen RS, Corlew RJ, Henson MA, Roberts AC, Mishina M, Watanabe M, Lipton SA, Nakanishi N, Pérez-Otaño I, Weinberg RJ, Philpot BD (2011) NR3A-containing NMDARs promote neurotransmitter release and spike timing-dependent plasticity. Nat Neurosci 14:338-344. CrossRef Medline
45. Lee J, Zhu WM, Stanic D, Finkelstein DI, Horne MH, Henderson J, Lawrence AJ, O'Connor L, Tomas D, Drago J, Horne MK (2008) Sprouting of dopamine terminals and altered dopamine release and uptake in Parkinsonian dyskinaesia. Brain 131:1574-1587. CrossRef Medline
46. Lee LJ, Iwasato T, Itohara S, Erzurumlu RS (2005) Exuberant thalamocortical axon arborization in cortex-specific NMDAR1 knockout mice. J Comp Neurol 485:280-292. CrossRef Medline
47. Li Y, Erzurumlu RS, Chen C, Jhaveri S, Tonegawa S (1994) Whisker-related neuronal patterns fail to develop in the trigeminal brainstem nuclei of NMDAR1 knockout mice. Cell 76:427-437. CrossRef Medline
48. Lien CC, Mu Y, Vargas-Caballero M, Poo MM (2006) Visual stimuliinduced LTD of GABAergic synapses mediated by presynaptic NMDA receptors. Nat Neurosci 9:372-380. CrossRef Medline
49. Lindsley CW, Zhao Z, Leister WH, O'Brien J, Lemaire W, Williams DL Jr, Chen TB, Chang RS, Burno M, Jacobson MA, Sur C, Kinney GG, Pettibone DJ, Tiller PR, Smith S, Tsou NN, Duggan ME, Conn PJ, Hartman GD (2006) Design, synthesis, and in vivo efficacy of glycine transporter-1 (GlyT1) inhibitors derived from a series of [4-phenyl-1-(propylsulfonyl)piperidin-4-yl]methyl benzamides. ChemMedChem 1:807-811. CrossRef Medline
50. Love S, Plaha P, Patel NK, Hotton GR, Brooks DJ, Gill SS (2005) Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain. Nat Med 11:703-704. CrossRef Medline
51. Marti MJ, James CJ, Oo TF, Kelly WJ, Burke RE (1997) Early developmental destruction of terminals in the striatal target induces apoptosis in dopamine neurons of the substantia nigra. J Neurosci 17:2030-2039. Medline
52. Martina M, Gorfinkel Y, Halman S, Lowe JA, Periyalwar P, Schmidt CJ, Bergeron R (2004) Glycine transporter type 1 blockade changes NMDA receptor-mediated responses and LTP in hippocampal CA1 pyramidal cells by altering extracellular glycine levels. J Physiol 557:489-500. CrossRef Medline
53. Martin-Facklam M, Pizzagalli F, Zhou Y, Ostrowitzki S, Raymont V, Brašić JR, Parkar N, Umbricht D, Dannals RF, Goldwater R, Wong DF (2013) Glycine transporter type 1 occupancy by bitopertin: a positron emission tomography study in healthy volunteers. Neuropsychopharmacology 38: 504-512. CrossRef Medline
54. Matsuda W, Furuta T, Nakamura KC, Hioki H, Fujiyama F, Arai R, Kaneko T (2009) Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum. J Neurosci 29:444-453. CrossRef Medline
55. Matsushita N, Okada H, Yasoshima Y, Takahashi K, Kiuchi K, Kobayashi K (2002) Dynamics of tyrosine hydroxylase promoter activity during midbrain dopaminergic neuron development. J Neurochem 82:295-304. CrossRef Medline
56. Miller GW, Erickson JD, Perez JT, Penland SN, Mash DC, Rye DB, Levey AI (1999) Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in Parkinson's disease. Exp Neurol 156:138-148. CrossRef Medline
57. Moss J, Bolam JP (2008) A dopaminergic axon lattice in the striatum and its relationship with cortical and thalamic terminals. J Neurosci 28:11221-11230. CrossRef Medline
58. Onn SP, Berger TW, Stricker EM, Zigmond MJ (1986) Effects of intraventricular 6-hydroxydopamine on the dopaminergic innervation of striatum: histochemical and neurochemical analysis. Brain Res 376:8-19. CrossRef Medline
59. Papouin T, Ladépêche L, Ruel J, Sacchi S, Labasque M, Hanini M, Groc L, Pollegioni L, Mothet JP, Oliet SH (2012) Synaptic and extrasynaptic NMDA receptors are gated by different endogenous co-agonists. Cell 150:633-646. CrossRef Medline
60. Parpura V, Zorec R (2010) Gliotransmission: exocytotic release from astrocytes. Brain Res Rev 63:83-92. CrossRef Medline
61. Pearce IA, Cambray-Deakin MA, Burgoyne RD (1987) Glutamate acting on NMDA receptors stimulates neurite outgrowth from cerebellar granule cells. FEBS Lett 223:143-147. CrossRef Medline
62. Pinard E, Alanine A, Alberati D, Bender M, Borroni E, Bourdeaux P, Brom V, Burner S, Fischer H, Hainzl D, Halm R, Hauser N, Jolidon S, Lengyel J, Marty HP, Meyer T, MoreauJL, MoryR, Narquizian R, NettekovenM, et al. (2010) Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-(S)-2,2,2-trifluoro-1-methylethoxy) phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia. J Med Chem 53:4603-4614. CrossRef Medline
63. Przedborski S, Levivier M, Jiang H, Ferreira M, Jackson-Lewis V, Donaldson D, Togasaki DM (1995) Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine. Neuroscience 67:631-647. CrossRef Medline
64. Pugh JR, Jahr CE (2011) NMDA receptor agonists fail to alter release from cerebellar basket cells. J Neurosci 31:16550-16555. CrossRef Medline
65. Raiteri L, Raiteri M (2010) Functional 'glial' GLYT1 glycine transporters expressed in neurons. J Neurochem 114:647-653. CrossRef Medline
66. Rangasamy SB, Soderstrom K, Bakay RA, Kordower JH (2010) Neurotrophic factor therapy for Parkinson's disease. Prog Brain Res 184:237-264. CrossRef Medline
67. Rashid NA, Cambray-Deakin MA (1992) N-methyl-D-aspartate effects on the growth, morphology and cytoskeleton of individual neurons in vitro. Brain Res Dev Brain Res 67:301-308. CrossRef Medline
68. Rice ME, Cragg SJ (2008) Dopamine spillover after quantal release: rethinking dopamine transmission in the nigrostriatal pathway. Brain Res Rev 58:303-313. CrossRef Medline
69. Rosenblad C, Kirik D, Björklund A (2000) Sequential administration of GDNFinto the substantia nigra and striatum promotes dopamine neuron survival and axonal sprouting but not striatal reinnervation or functional recovery in the partial 6-OHDA lesion model. Exp Neurol 161:503-516. CrossRef Medline
70. Ruthazer ES, Cline HT (2004) Insights into activity-dependent map formation from the retinotectal system: a middle-of-the-brain perspective. J Neurobiol 59:134-146. CrossRef Medline
71. Schmitz Y, Lee CJ, Schmauss C, Gonon F, Sulzer D (2001) Amphetamine distorts stimulation-dependent dopamine overflow: effects on D2 autoreceptors, transporters, and synaptic vesicle stores. J Neurosci 21:5916-5924. Medline
72. Schmitz Y, Benoit-Marand M, Gonon F, Sulzer D (2003) Presynaptic regulation of dopaminergic neurotransmission. J Neurochem 87:273-289. CrossRef Medline
73. Schmitz Y, Luccarelli J, Kim M, Wang M, Sulzer D (2009) Glutamate controls growth rate and branching of dopaminergic axons. J Neurosci 29: 11973-11981. CrossRef Medline
74. Smith KE, Borden LA, Hartig PR, Branchek T, Weinshank RL (1992) Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors. Neuron 8:927-935. CrossRef Medline
75. Stanic D, Finkelstein DI, Bourke DW, Drago J, Horne MK (2003) Timecourse of striatal re-innervation following lesions of dopaminergic SNpc neurons of the rat. Eur J Neurosci 18:1175-1188. CrossRef Medline
76. Stuber GD, Hnasko TS, Britt JP, Edwards RH, Bonci A (2010) Dopaminergic terminals in the nucleus accumbens but not the dorsal striatum corelease glutamate. J Neurosci 30:8229-8233. CrossRef Medline
77. Sulzer D, Joyce MP, Lin L, Geldwert D, Haber SN, Hattori T, Rayport S (1998) Dopamine neurons make glutamatergic synapses in vitro. J Neurosci 18:4588-4602. Medline
78. Tatton WG, Kwan MM, Verrier MC, Seniuk NA, Theriault E (1990) MPTP produces reversible disappearance of tyrosine hydroxylase-containing retinal amacrine cells. Brain Res 527:21-31. CrossRef Medline
79. Tritsch NX, Ding JB, Sabatini BL (2012) Dopaminergic neurons inhibit striatal output through noncanonical release of GABA. Nature 490:262-266. CrossRef Medline
80. Tzingounis AV, Nicoll RA (2004) Presynaptic NMDA receptors get into the act. Nat Neurosci 7:419-420. CrossRef Medline
81. Wang PY, Petralia RS, Wang YX, Wenthold RJ, Brenowitz SD (2011) Functional NMDA receptors at axonal growth cones of young hippocampal neurons. J Neurosci 31:9289-9297. CrossRef Medline
82. West MO, Carelli RM, Pomerantz M, Cohen SM, Gardner JP, Chapin JK, Woodward DJ (1990) A region in the dorsolateral striatum of the rat exhibiting single-unit correlations with specific locomotor limb movements. J Neurophysiol 64:1233-1246. Medline
83. Wolkenberg SE, Zhao Z, Wisnoski DD, Leister WH, O'Brien J, Lemaire W, Williams DL Jr, Jacobson MA, Sur C, Kinney GG, Pettibone DJ, Tiller PR, Smith S, Gibson C, Ma BK, Polsky-Fisher SL, Lindsley CW, Hartman GD (2009) Discovery of GlyT1 inhibitors with improved pharmacokinetic properties. Bioorg Med Chem Lett 19:1492-1495. CrossRef Medline
84. Zafra F, Gomeza J, Olivares L, Aragón C, Giménez C (1995) Regional distribution and developmental variation of the glycine transporters GLYT1 and GLYT2 in the rat CNS. Eur J Neurosci 7:1342-1352. CrossRef Medline
85. Zheng JQ, Wan JJ, Poo MM (1996) Essential role of filopodia in chemotropic turning of nerve growth cone induced by a glutamate gradient. J Neurosci 16:1140-1149. Medline
86. Zweifel LS, Fadok JP, Argilli E, Garelick MG, Jones GL, Dickerson TM, Allen JM, Mizumori SJ, Bonci A, Palmiter RD (2011) Activation of dopamine neurons is critical for aversive conditioning and prevention of generalized anxiety. Nat Neurosci 14:620-626. CrossRef Medline