The Long Way from Complex Phenotypes to Genes: The Story of Rat Chromosome 4 and Its Behavioral Effects


Quantitative trait loci (QTLs) mapping has been performed during the past decades in an attempt to identify genes, gene products and mechanisms underlying numerous quantitative traits. It’s a strategy based on natural variations in genes and gene products, which facilitates translation from animal models to human clinical conditions. Our team has shown that the inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) differ with respect to several emotionality- related behaviors, one of which (inner locomotion in the open field) was strongly influenced by a QTL (Anxrr16) on rat chromosome 4. Since then, several other studies not only corroborated the initial description of Anxrr16, but also extrapolated its effects to a broader context (rats from both sexes and regardless of the estrous cycle phase) and suggested that this same region influences other emotionality-related behaviors as well as alcohol intake. Other QTLs affecting neurobiological traits were also found on rat chromosome 4 and several candidate genes have been pointed out as possibly influencing those phenotypes. Altogether, these studies suggest that rat chromosome 4 constitutes an interesting target for the study of the molecular bases of anxiety and other traits related to emotional reactivity.

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Medeiros, G. , Corrêa, F. , Corvino, M. , Izídio, G. and Ramos, A. (2014) The Long Way from Complex Phenotypes to Genes: The Story of Rat Chromosome 4 and Its Behavioral Effects. World Journal of Neuroscience, 4, 203-215. doi: 10.4236/wjns.2014.43024.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Plomin, R., Owen, M.J. and McGuffin, P. (1994) The Genetic Basis of Complex Human Behaviors. Science, 264, 1733-1739.
[2] Flint, J., Valdar, W., Shifman, S. and Mott, R. (2005) Strategies for Mapping and Cloning Quantitative Trait Genes in Rodents. Nature Reviews Genetic, 6, 271-286.
[3] Mauricio, R. (2001) Mapping Quantitative Trait Loci in Plants: Uses and Caveats for Evolutionary Biology. Nature Reviews Genetic, 2, 370-381.
[4] Moore, K.J. and Nagle, D.L. (2000) Complex Trait Analysis in the Mouse: The Strengths, the Limitations and the Promise yet to Come. Annual Review of Genetics, 34, 653-686.
[5] Paterson, A.H., Lander, E.S., Hewitt, J.D., Peterson, S., Lincoln, S.E. and Tanksley, S.D. (1988) Resolution of Quantitative Traits into Mendelian Factors by Using a Complete Linkage Map of Restriction Fragment Length Polymorphisms. Nature, 335, 721-726.
[6] Hilbert, P., Lindpaintner, K., Beckmann, J.S., Serikawa, T., Soubrier, F., Dubay, C., Cartwright, P., De Gouyon, B., Julier, C., Takahasi, S., et al. (1991) Chromosomal Mapping of Two Genetic Loci Associated with Blood-Pressure Regulation in Hereditary Hypertensive Rats. Nature, 353, 521-529.
[7] Flint, J., Corley, R., DeFries, J.C., Fulker, D.W., Gray, J.A., Miller, S. and Collins, A.C. (1995) A Simple Genetic Basis for a Complex Psychological Trait in Laboratory Mice. Science, 269, 1432-1435.
[8] Moisan, M.P., Courvoisier, H., Bihoreau, M.T., Gauguier, D., Hendley, E.D., Lathrop, M., James, M.R. and Mormede, P. (1996) A Major Quantitative Trait Locus Influences Hyperactivity in the WKHA Rat. Nature Genetics, 14, 471-473.
[9] Ramos, A., Moisan, M.P., Chaouloff, F., Mormede, C. and Mormede, P. (1999) Identification of Female-Specific QTLs Affecting an Emotionality-Related Behavior in Rats. Molecular Psychiatry, 4, 453-462.
[10] Remmers, E.F., Longman, R.E., Du, Y., O’Hare, A., Cannon, G.W., Griffiths, M.M. and Wilder, R.L. (1996) A Genome Scan Localizes Five Non-Mhc Loci Controlling Collagen-Induced Arthritis in Rats. Nature Genetics, 14, 82-85.
[11] Aitman, T.J., Gotoda, T., Evans, A.L., Imrie, H., Heath, K.E., Trembling, P.M., Truman, H., Wallace, C.A., Rahman, A., Dore, C., Flint, J., Kren, V., Zidek, V., Kurtz, T.W., Pravenec, M. and Scott, J. (1997) Quantitative Trait Loci for Cellular Defects in Glucose and Fatty Acid Metabolism in Hypertensive Rats. Nature Genetics, 16, 197-201.
[12] Conti, L.H., Jirout, M., Breen, L., Vanella, J.J., Schork, N.J. and Printz, M.P. (2004) Identification of Quantitative Trait Loci for Anxiety and Locomotion Phenotypes in Rat Recombinant Inbred Strains. Behavior Genetics, 34, 93-103.
[13] Bice, P., Foroud, T., Bo, R., Castelluccio, P., Lumeng, L., Li, T.K. and Carr, L.G. (1998) Genomic Screen for QTLs Underlying Alcohol Consumption in the P and NP Rat Lines. Mammalian Genome, 9, 949-955.
[14] Potenza, M.N., Brodkin, E.S., Joe, B., Luo, X., Remmers, E.F., Wilder, R.L., Nestler, E.J. and Gelernter, J. (2004) Genomic Regions Controlling Corticosterone Levels in Rats. Biological Psychiatry, 55, 634-641.
[15] Gill, K.J. and Boyle, A E. (2005) Quantitative Trait Loci for Novelty/Stress-Induced Locomotor Activation in Recombinant Inbred (RI) and Recombinant Congenic (RC) Strains of Mice. Behavioural Brain Research, 161, 113-124.
[16] Leduc, M.S., Blair, R.H., Verdugo, R.A., Tsaih, S.W., Walsh, K., Churchill, G.A. and Paigen, B. (2012) Using Bioinformatics and Systems Genetics to Dissect HDL-Cholesterol Genetics in an MRL/MpJ × SM/J Intercross. Journal of Lipid Research, 53, 1163-1175.
[17] Tsuji, A.B., Sugyo, A., Ogiu, T., Sagara, M., Kimura, T., Ishikawa, A., Sudo, H., Ohtsuki, M., Aburatani, H., Imai, T. and Harada, Y.N. (2005) Fine Mapping of Radiation Susceptibility and Gene Expression Analysis of LEC Congenic Rat Lines. Genomics, 86, 271-279.
[18] Marta, M., Stridh, P., Becanovic, K., Gillett, A., Ockinger, J., Lorentzen, J.C., Jagodic, M. and Olsson, T. (2010) Multiple Loci Comprising Immune-Related Genes Regulate Experimental Neuroinflammation EAE-Regulating QTLs on RN04. Genes & Immunity, 11, 21-36.
[19] Llamas, B., Contesse, V., Guyonnet-Duperat, V., Vaudry, H., Mormede, P. and Moisan, M.P. (2005) QTL Mapping for Traits Associated with Stress Neuroendocrine Reactivity in Rats. Mammalian Genome, 16, 505-515.
[20] Hofstetter, J.R., Mayeda, A.R., Possidente, B. and Nurnberger Jr., J.I. (1995) Quantitative Trait Loci (QTL) for Circadian Rhythms of Locomotor Activity in Mice. Behavior Genetics, 25, 545-556.
[21] Ramos, A., Berton, O., Mormede, P. and Chaouloff, F. (1997) A Multiple-Test Study of Anxiety-Related Behaviours in Six Inbred Rat Strains. Behavioural Brain Research, 85, 57-69.
[22] Ramos, A., Mellerin, Y., Mormede, P. and Chaouloff, F. (1998) A Genetic and Multifactorial Analysis of AnxietyRelated Behaviours in Lewis and SHR Intercrosses. Behavioural Brain Research, 96, 195-205.
[23] Laulederkind, S.J., Hayman, G.T., Wang, S.J., Smith, J.R., Lowry, T.F., Nigam, R., Petri, V., De Pons, J., Dwinell, M.R. and Shimoyama, M. (2013) The Rat Genome Database 2013—Data, Tools and Users. Briefings in Bioinformatics, 14, 520-526.
[24] Caldarone, B., Saavedra, C., Tartaglia, K., Wehner, J.M., Dudek, B.C. and Flaherty, L. (1997) Quantitative Trait Loci Analysis Affecting Contextual Conditioning in Mice. Nature Genetics, 17, 335-337.
[25] Silva, G.J., Pereira, A.C., Krieger, E.M. and Krieger, J.E. (2007) Genetic Mapping of a New Heart Rate QTL on Chromosome 8 of Spontaneously Hypertensive Rats. BMC Medical Genetics, 8, 17.
[26] Carr, L.G., Foroud, T., Bice, P., Gobbett, T., Ivashina, J., Edenberg, H., Lumeng, L. and Li, T.K. (1998) A Quantitative Trait Locus for Alcohol Consumption in Selectively Bred Rat Lines. Alcoholism: Clinical and Experimental Research, 22, 884-887.
[27] Terenina-Rigaldie, E., Moisan, M.P., Colas, A., Beauge, F., Shah, K.V., Jones, B.C. and Mormede, P. (2003) Genetics of Behaviour: Phenotypic and Molecular Study of Rats Derived From Highand Low-Alcohol Consuming Lines. Pharmacogenetics, 13, 543-554.
[28] Flint, J. (2002) Genetic Effects on an Animal Model of Anxiety. FEBS Letters, 529, 131-134.
[29] Abiola, O., Angel, J.M., Avner, P., Bachmanov, A.A., Belknap, J.K., Bennett, B., Blankenhorn, E.P., Blizard, D.A., Bolivar, V., Brockmann, G.A., Buck, K.J., Bureau, J.F., Casley, W.L., Chesler, E.J., Cheverud, J.M., Churchill, G.A., Cook, M., Crabbe, J.C., Crusio, W.E., Darvasi, A., De Haan, G., Dermant, P., Doerge, R.W., Elliot, R.W., Farber, C.R., Flaherty, L., Flint, J., Gershenfeld, H., Gibson, J.P., Gu, J., Gu, W., Himmelbauer, H., Hitzemann, R., Hsu, H.C., Hunter, K., Iraqi, F.F., Jansen, R.C., Johnson, T.E., Jones, B.C., Kempermann, G., Lammert, F., Lu, L., Manly, K.F., Matthews, D.B., Medrano, J.F., Mehrabian, M., Mittlemann, G., Mock, B.A., Mogil, J.S., Montagutelli, X., Morahan, G., Mountz, J.D., Nagase, H., Nowakowski, R.S., O’Hara, B.F., Osadchuk, A.V., Paigen, B., Palmer, A.A., Peirce, J.L., Pomp, D., Rosemann, M., Rosen, G.D., Schalkwyk, L.C., Seltzer, Z., Settle, S., Shimomura, K., Shou, S., Sikela, J.M., Siracusa, L.D., Spearow, J.L., Teuscher, C., Threadgill, D.W., Toth, L.A., Toye, A.A., Vadasz, C., Van Zant, G., Wakeland, E., Williams, R.W., Zhang, H.G. and Zou, F. (2003) The Nature and Identification of Quantitative Trait Loci: A Community’s View. Nature Reviews Genetics, 4, 911-916.
[30] Mackay, T.F., Stone, E.A. and Ayroles, J.F. (2009) The Genetics of Quantitative Traits: Challenges and Prospects. Nature Reviews Genetics, 10, 565-577.
[31] Doerge, R.W. and Churchill, G.A. (1996) Permutation Tests for Multiple Loci Affecting a Quantitative Character. Genetics, 142, 285-294.
[32] Flint, J. (2003) Analysis of Quantitative Trait Loci that Influence Animal Behavior. Journal of Neurobiology, 54, 46-77.
[33] Izidio, G.S., Oliveira, L.C., Oliveira, L.F., Pereira, E., Wehrmeister, T.D. and Ramos, A. (2011) The Influence of Sex and Estrous Cycle on QTL for Emotionality and Ethanol Consumption. Mammalian Genome, 22, 329-340.
[34] Hovatta, I. and Barlow, C. (2008) Molecular Genetics of Anxiety in Mice and Men. Annals of Medicine, 40, 92-109.
[35] Fernandez-Teruel, A., Escorihuela, R.M., Gray, J.A., Aguilar, R., Gil, L., Gimenez-Llort, L., Tobena, A., Bhomra, A., Nicod, A., Mott, R., Driscoll, P., Dawson, G.R. and Flint, J. (2002) A Quantitative Trait Locus Influencing Anxiety in the Laboratory Rat. Genome Research, 12, 618-626.
[36] Gershenfeld, H.K. and Paul, S.M. (1997) Mapping Quantitative Trait Loci for Fear-Like Behaviors in Mice. Genomics, 46, 1-8.
[37] Mormede, P., Moneva, E., Bruneval, C., Chaouloff, F. and Moisan, M.P. (2002) Marker-Assisted Selection of a NeuroBehavioural Trait Related to Behavioural Inhibition in the SHR Strain, an Animal Model of ADHD. Genes, Brain and Behavior, 1, 111-116.
[38] Vendruscolo, L.F., Terenina-Rigaldie, E., Raba, F., Ramos, A., Takahashi, R.N. and Mormede, P. (2006) Evidence for a Female-Specific Effect of a Chromosome 4 Locus on Anxiety-Related Behaviors and Ethanol Drinking in Rats. Genes, Brain and Behavior, 5, 441-450.
[39] Vendruscolo, L.F., Terenina-Rigaldie, E., Raba, F., Ramos, A., Takahashi, R.N. and Mormede, P. (2006) A QTL on Rat Chromosome 7 Modulates Prepulse Inhibition, a Neuro-Behavioral Trait of ADHD, in a Lewis X SHR Intercross. Behavioral and Brain Functions, 2, 21.
[40] Hameister, T.M., Izidio, G.S., Valiati, V.H. and Ramos, A. (2008) Association of a Locus on Rat Chromosome 4 with Anxiety-Related Behaviors in Two Selectively Bred Rat Lines. Genetics and Molecular Biology, 31, 843-849.
[41] Chiavegatto, S., Izidio, G.S., Mendes-Lana, A., Aneas, I., Freitas, T.A., Torrao, A.S., Conceicao, I.M., Britto, L.R. and Ramos, A. (2009) Expression of α-Synuclein Is Increased in the Hippocampus of Rats with High Levels of Innate Anxiety. Molecular Psychiatry, 14, 894-905.
[42] Mori, F., Tanji, K., Yoshimoto, M., Takahashi, H. and Wakabayashi, K. (2002) Immunohistochemical Comparison of Alphaand Beta-Synuclein in Adult Rat Central Nervous System. Brain Research, 941, 118-126.
[43] Perez, R.G., Waymire, J.C., Lin, E., Liu, J.J., Guo, F. and Zigmond, M.J. (2002) A Role for Alpha-Synuclein in the Regulation of Dopamine Biosynthesis. Journal of Neuroscience, 22, 3090-3099.
[44] Kaplan, B., Ratner, V. and Haas, E. (2003) α-Synuclein: Its Biological Function and Role in Neurodegenerative Diseases. Journal of Molecular Neuroscience, 20, 83-92.
[45] Bonsch, D., Reulbach, U., Bayerlein, K., Hillemacher, T., Kornhuber, J. and Bleich, S. (2004) Elevated Alpha Synuclein Mrna Levels Are Associated with Craving in Patients with Alcoholism. Biological Psychiatry, 56, 984-986.
[46] Liang, T., Spence, J., Liu, L., Strother, W.N., Chang, H.W., Ellison, J.A., Lumeng, L., Li, T.K., Foroud, T. and Carr, L.G. (2003) α-Synuclein Maps to a Quantitative Trait Locus for Alcohol Preference and Is Differentially Expressed in Alcohol-Preferring and -Nonpreferring Rats. Proceedings of the National Academy of Sciences of the United States of America, 100, 4690-4695.
[47] Richard, I.H. (2005) Anxiety Disorders in Parkinson’s Disease. Advances in Neurology, 96, 42-55.
[48] Morris, E.P., Stewart, S.H. and Ham, L.S. (2005) The Relationship between Social Anxiety Disorder and Alcohol Use Disorders: A Critical Review. Clinical Psychology Review, 25, 734-760.
[49] Vendruscolo, L.F., Vendruscolo, J.C., Terenina, E., Ramos, A., Takahashi, R.N. and Mormede, P. (2009) Marker-Assisted Dissection of Genetic Influences on Motor and Neuroendocrine Sensitization to Cocaine in Rats. Genes, Brain and Behavior, 8, 267-274.
[50] Cador, M., Dulluc, J. and Mormede, P. (1993) Modulation of the Locomotor Response to Amphetamine by Corticosterone. Neuroscience, 56, 981-988.
[51] Przegalinski, E., Filip, M., Siwanowicz, J. and Nowak, E. (2000) Effect of Adrenalectomy and Corticosterone on Cocaine-Induced Sensitization in Rats. Journal of Physiology and Pharmacology, 51, 193-204.
[52] Rivet, J.M., Stinus, L., Lemoal, M. and Mormede, P. (1989) Behavioral Sensitization to Amphetamine Is Dependent on Corticosteroid Receptor Activation. Brain Research, 498, 149-153.
[53] Mello, A.F., Mello, M.F., Carpenter, L.L. and Price, L.H. (2003) Update on Stress and Depression: The Role of the Hypothalamic-Pituitary-Adrenal (HPA) Axis. Revista Brasileira de Psiquiatria, 25, 231-238.
[54] De Medeiros, G.F., Pereira, E., Granzotto, N. and Ramos, A. (2013) Low-Anxiety Rat Phenotypes Can Be Further Reduced through Genetic Intervention. PLoS ONE, 8, Article ID: e83666.
[55] Potenza, M.N., Brodkin, E.S., Joe, B., Luo, X., Remmers, E.F., Wilder, R.L., Nestler, E.J. and Gelernter, J. (2004) Genomic Regions Controlling Corticosterone Levels in Rats. Biological Psychiatry, 55, 634-641.
[56] Carr, L.G., Foroud, T., Bice, P., Gobbett, T., Ivashina, J., Edenberg, H., Lumeng, L. and Li, T.K. (1998) A Quantitative Trait Locus for Alcohol Consumption in Selectively Bred Rat Lines. Alcoholism: Clinical and Experimental Research, 22, 884-887.
[57] Koller, D.L., Liu, L., Alam, I., Sun, Q., Econs, M.J., Foroud, T. and Turner, C.H. (2008) Linkage Screen for BMD Phenotypes in Male and Female COP and DA Rat Strains. Journal of Bone and Mineral Research, 23, 1382-1388.
[58] Garrett, M.R., Joe, B., Dene, H. and Rapp, J.P. (2002) Identification of Blood Pressure Quantitative Trait Loci that Differentiate Two Hypertensive Strains. Journal of Hypertension, 20, 2399-2406.
[59] Kloting, N., Wilke, B. and Kloting, I. (2005) Alleles on Rat Chromosome 4 (D4Got41-Fabp1/Tacr1) Regulate Subphenotypes of Obesity. Obesity Research, 13, 589-595.
[60] Ehlers, C.L., Li, T.K., Lumeng, L., Hwang, B.H., Somes, C., Jimenez, P. and Mathe, A.A. (1998) Neuropeptide Y Levels in Ethanol-Naive Alcohol-Preferring and Nonpreferring Rats and in Wistar Rats after Ethanol Exposure. Alcoholism: Clinical and Experimental Research, 22, 1778-1782.
[61] Stewart, R.B., Gatto, G.J., Lumeng, L., Li, T.K. Andmurphy, J.M. (1993) Comparison of Alcohol-Preferring (P) and Nonpreferring (NP) Rats on Tests of Anxiety and for the Anxiolytic Effects of Ethanol. Alcohol, 10, 1-10.
[62] Mori, F., Nishie, M., Kakita, A., Yoshimoto, M., Takahashi, H. and Wakabayashi, K. (2006) Relationship among αSynuclein Accumulation, Dopamine Synthesis, and Neurodegeneration in Parkinson Disease Substantia Nigra. Journal of Neuropathology & Experimental Neurology, 65, 808-815.
[63] Polymeropoulos, M.H., Higgins, J.J., Golbe, L.I., Johnson, W.G., Ide, S.E., Di Iorio, G., Sanges, G., Stenroos, E.S., Pho, L.T., Schaffer, A.A., Lazzarini, A.M., Nussbaum, R.L. and Duvoisin, R.C. (1996) Mapping of a Gene for Parkinson’s Disease to Chromosome 4q21-q23. Science, 274, 1197-1199.
[64] Kurz, A., Double, K.L., Lastres-Becker, I., Tozzi, A., Tantucci, M., Bockhart, V., Bonin, M., Garcia-Arencibia, M., Nuber, S., Schlaudraff, F., Liss, B., Fernandez-Ruiz, J., Gerlach, M., Wullner, U., Luddens, H., Calabresi, P., Auburger, G. and Gispert, S. (2010) A53T-Alpha-Synuclein Overexpression Impairs Dopamine Signaling and Striatal Synaptic Plasticity in Old Mice. PLoS ONE, 5, Article ID: E11464.
[65] Le-Niculescu, H., Mcfarland, M.J., Ogden, C.A., Balaraman, Y., Patel, S., Tan, J., Rodd, Z.A., Paulus, M., Geyer, M.A., Edenberg, H.J., Glatt, S.J., Faraone, S.V., Nurnberger, J.I., Kuczenski, R., Tsuang, M.T. and Niculescu, A.B. (2008) Phenomic, Convergent Functional Genomic, and Biomarker Studies in a Stress-Reactive Genetic Animal Model of Bipolar Disorder and Co-Morbid Alcoholism. American Journal of Medical Genetics Part B, 147B, 134-166.
[66] Carr, L.G., Kimpel, M.W., Liang, T., Mcclintick, J.N., Mccall, K., Morse, M. and Edenberg, H.J. (2007) Identification of Candidate Genes for Alcohol Preference by Expression Profiling of Congenic Rat Strains. Alcoholism: Clinical and Experimental Research, 31, 1089-1098.
[67] Spence, J., Liang, T., Foroud, T., Lo, D. and Carr, L. (2005) Expression Profiling and QTL Analysis: A Powerful Complementary Strategy in Drug Abuse Research. Addiction Biology, 10, 47-51.
[68] Greetfeld, M., Schmidt, M.V., Ganea, K., Sterlemann, V., Liebl, C. and Muller, M.B. (2009) A Single Episode of Restraint Stress Regulates Central Corticotrophin-Releasing Hormone Receptor Expression and Binding in Specific Areas of the Mouse Brain. Journal of Neuroendocrinology, 21, 473-480.
[69] Heilig, M. and Koob, G.F. (2007) A Key Role for Corticotropin-Releasing Factor in Alcohol Dependence. Trends in Neuroscience, 30, 399-406.
[70] Guillaume, S., Perroud, N., Jollant, F., Jaussent, I., Olie, E., Malafosse, A. and Courtet, P. (2013) HPA Axis Genes May Modulate the Effect of Childhood Adversities on Decision-Making in Suicide Attempters. Journal of Psychiatric Research, 47, 259-265.
[71] Turecki, G., Ernst, C., Jollant, F., Labonte, B. and Mechawar, N. (2012) The Neurodevelopmental Origins of Suicidal Behavior. Trends in Neuroscience, 35, 14-23.
[72] Sharpe, A.L., Coste, S.C., Burkhart-Kasch, S., Li, N., Stenzel-Poore, M.P. and Phillips, T.J. (2005) Mice Deficient in Corticotropin-Releasing Factor Receptor Type 2 Exhibit Normal Ethanol-Associated Behaviors. Alcoholism: Clinical and Experimental Research, 29, 1601-1609.
[73] Yong, W., Spence, J.P., Eskay, R., Fitz, S.D., Damadzic, R., Lai, D., Foroud, T., Carr, L.G., Shekhar, A., Chester, J.A., Heilig, M. and Liang, T. (2014) Alcohol-Preferring Rats Show Decreased Corticotropin-Releasing Hormone-2 Receptor Expression and Differences in HPA Activation Compared to Alcohol-Nonpreferring Rats. Alcoholism: Clinical and Experimental Research, 38, 1275-1283.
[74] Srivastava, S., Osten, P., Vilim, F.S., Khatri, L., Inman, G., States, B., Daly, C., Desouza, S., Abagyan, R., Valtschanoff, J.G., Weinberg, R.J. and Ziff, E.B. (1998) Novel Anchorage of GluR2/3 to the Postsynaptic Density by the AMPA Receptor-Binding Protein ABP. Neuron, 21, 581-591.
[75] Dong, H., O’Brien, R.J., Fung, E.T., Lanahan, A.A., Worley, P.F. and Huganir, R.L. (1997) GRIP: A Synaptic PDZ Domain-Containing Protein that Interacts with AMPA Receptors. Nature, 386, 279-284.
[76] Bliss, T.V. and Collingridge, G.L. (1993) A Synaptic Model of Memory: Long-Term Potentiation in the Hippocampus. Nature, 361, 31-39.
[77] Malenka, R.C. and Bear, M.F. (2004) LTP and LTD: An Embarrassment of Riches. Neuron, 44, 5-21.
[78] Martin, S.J., Grimwood, P.D. and Morris, R.G. (2000) Synaptic Plasticity and Memory: An Evaluation of the Hypothesis. Annual Review of Neuroscience, 23, 649-711.
[79] Malinow, R. and Malenka, R.C. (2002) AMPA Receptor Trafficking and Synaptic Plasticity. Annual Review of Neuroscience, 25, 103-126.
[80] Osten, P., Khatri, L., Perez, J.L., Kohr, G., Giese, G., Daly, C., Schulz, T.W., Wensky, A., Lee, L.M. and Ziff, E.B. (2000) Mutagenesis Reveals a Role for ABP/GRIP Binding to GluR2 in Synaptic Surface Accumulation of the AMPA Receptor. Neuron, 27, 313-325.
[81] Solberg, L.C., Baum, A.E., Ahmadiyeh, N., Shimomura, K., Li, R., Turek, F.W., Takahashi, J.S., Churchill, G.A. and Redei, E.E. (2006) Genetic Analysis of the Stress-Responsive Adrenocortical Axis. Physiological Genomics, 27, 362369.

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