Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism

Science Translational Medicine

Volumn 7, Issue 271, 2015, Pages

  Peñagarikano, Olga ^a,b   Lázaro, María T ^a   Lu, Xiao Hong ^b   Gordon, Aaron ^c   Dong, Hongmei ^a   Lam, Hoa A ^b   Peles, Elior ^c   Maidment, Nigel T ^b   Murphy, Niall P ^b   Yang, X William ^b   Golshani, Peyman ^a,d,e   Geschwind, Daniel H ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e VA GREATER LOS ANGELES HEALTHCARE SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOZAPINE N OXIDE; OXYTOCIN; CNTNAP2 PROTEIN, MOUSE; MEMBRANE PROTEIN; NERVE PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AUTISM; BEHAVIOR DISORDER; BRAIN LEVEL; CONTROLLED STUDY; DRUG EFFECT; DRUG SCREENING; FEMALE; HORMONE RELEASE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; IN VIVO STUDY; JUVENILE ANIMAL; MALE; MOUSE; NERVE CELL; NONHUMAN; PERINATAL PERIOD; SINGLE DRUG DOSE; SOCIAL BEHAVIOR; SOCIAL INTERACTION; ANIMAL; ANIMAL BEHAVIOR; AUTISTIC DISORDER; DISEASE MODEL; DRUG EFFECTS; HUMAN; KNOCKOUT MOUSE; METABOLISM; MUTANT MOUSE STRAIN; NEWBORN; PATHOLOGY;

ANIMALS; ANIMALS, NEWBORN; AUTISTIC DISORDER; BEHAVIOR, ANIMAL; DISEASE MODELS, ANIMAL; HUMANS; MEMBRANE PROTEINS; MICE, KNOCKOUT; MICE, MUTANT STRAINS; NERVE TISSUE PROTEINS; NEURONS; OXYTOCIN; PARAVENTRICULAR HYPOTHALAMIC NUCLEUS; SOCIAL BEHAVIOR;

EID: 84921792372     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3010257     Document Type: Article

References (76)

1. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Publishing, Washington, DC, ed. 5 2013).
2. D. H. Geschwind, Advances in autism. Annu. Rev. Med. 60, 367-380 (2009).
3. I. Iossifov, B. J. O'Roak, S. J. Sanders, M. Ronemus, N. Krumm, D. Levy, H. A. Stessman, K. T. Witherspoon, L. Vives, K. E. Patterson, J. D. Smith, B. Paeper, D. A. Nickerson, J. Dea, S. Dong, L. E. Gonzalez, J. D. Mandell, S. M. Mane, M. T. Murtha, C. A. Sullivan, M. F. Walker, Z. Waqar, L. Wei, A. J. Willsey, B. Yamrom, Y. H. Lee, E. Grabowska, E. Dalkic, Z. Wang, S. Marks, P. Andrews, A. Leotta, J. Kendall, I. Hakker, J. Rosenbaum, B. Ma, L. Rodgers, J. Troge, G. Narzisi, S. Yoon, M. C. Schatz, K. Ye, W. R. McCombie, J. Shendure, E. E. Eichler, M. W. State,M.Wigler, The contribution of de novo coding mutations to autism spectrum disorder. Nature 515, 216-221 (2014).
4. S. De Rubeis, X. He, A. P. Goldberg, C. S. Poultney, K. Samocha, A. E. Cicek, Y. Kou, L. Liu, M. Fromer, S. Walker, T. Singh, L. Klei, J. Kosmicki, F. Shih-Chen, B. Aleksic, M. Biscaldi, P. F. Bolton, J. M. Brownfeld, J. Cai, N. G. Campbell, A. Carracedo, M. H. Chahrour, A. G. Chiocchetti, H. Coon, E. L. Crawford, S. R. Curran, G. Dawson, E. Duketis, B. A. Fernandez, L. Gallagher, E. Geller, S. J. Guter, R. S. Hill, J. Ionita-Laza, P. Jimenz Gonzalez, H. Kilpinen, S. M. Klauck, A. Kolevzon, I. Lee, I. Lei, J. Lei, T. Lehtimäki, C. F. Lin, A. Ma'ayan, C. R. Marshall, A. L. McInnes, B. Neale, M. J. Owen, N. Ozaki, M. Parellada, J. R. Parr, S. Purcell, K. Puura, D. Rajagopalan, K. Rehnström, A. Reichenberg, A. Sabo, M. Sachse, S. J. Sanders, C. Schafer, M. Schulte-Rüther, D. Skuse, C. Stevens, P. Szatmari, K. Tammimies, O. Valladares, A. Voran, W. Li-San, L. A. Weiss, A. J. Willsey, T. W. Yu, K. Yuen; DDD Study; Homozygosity Mapping Collaborative for Autism; UK10K Consortium, E. H. Cook, C. M. Freitag, M. Gill, C. M. Hultman, T. Lehner, A. Palotie, G. D. Schellenberg, P. Sklar, M. W. State, J. S. Sutcliffe, C. A. Walsh, S.W. Scherer, M. E. Zwick, J. C. Barett, D. J. Cutler, K. Roeder, B. Devlin, M. J. Daly, J. D. Buxbaum, Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515, 209-215 (2014).
5. J. M. Berg, D. H. Geschwind, Autism genetics: Searching for specificity and convergence. Genome Biol. 13, 247 (2012).
6. H. Won, W. Mah, E. Kim, Autism spectrum disorder causes, mechanisms, and treatments: Focus on neuronal synapses. Front. Mol. Neurosci. 6, 19 (2013).
7. E. Ey, C. S. Leblond, T. Bourgeron, Behavioral profiles of mouse models for autism spectrum disorders. Autism Res. 4, 5-16 (2011).
8. J. N. Crawley, Translational animal models of autism and neurodevelopmental disorders. Dialogues Clin. Neurosci. 14, 293-305 (2012).
9. K. A. Strauss, E. G. Puffenberger, M. J. Huentelman, S. Gottlieb, S. E. Dobrin, J. M. Parod, D. A. Stephan, D. H. Morton, Recessive symptomatic focal epilepsy and mutant contactinassociated protein-like 2. N. Engl. J. Med. 354, 1370-1377 (2006).
10. O. Peñagarikano, B. S. Abrahams, E. I. Herman, K. D. Winden, A. Gdalyahu, H. Dong, L. I. Sonnenblick, R. Gruver, J. Almajano, A. Bragin, P. Golshani, J. T. Trachtenberg, E. Peles, D. H. Geschwind, Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell 147, 235-246 (2011).
11. T. R. Insel, The challenge of translation in social neuroscience: A review of oxytocin, vasopressin, and affiliative behavior. Neuron 65, 768-779 (2010).
12. H. E. Ross, L. J. Young, Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front. Neuroendocrinol. 30, 534-547 (2009).
13. S. Wu, M. Jia, Y. Ruan, J. Liu, Y. Guo, M. Shuang, X. Gong, Y. Zhang, X. Yang, D. Zhang, Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol. Psychiatry 58, 74-77 (2005).
14. R. P. Ebstein, S. Israel, E. Lerer, F. Uzefovsky, I. Shalev, I. Gritsenko, M. Riebold, S. Salomon, N. Yirmiya, Arginine vasopressin and oxytocin modulate human social behavior. Ann. N.Y. Acad. Sci. 1167, 87-102 (2009).
15. E. Lerer, S. Levi, S. Salomon, A. Darvasi, N. Yirmiya, R. P. Ebstein, Association between the oxytocin receptor (OXTR) gene and autism: Relationship to Vineland Adaptive Behavior Scales and cognition. Mol. Psychiatry 13, 980-988 (2008).
16. E. Lerer, S. Levi, S. Israel, M. Yaari, L. Nemanov, D. Mankuta, Y. Nurit, R. P. Ebstein, Low CD38 expression in lymphoblastoid cells and haplotypes are both associated with autism in a family-based study. Autism Res. 3, 293-302 (2010).
17. T. Munesue, S. Yokoyama, K. Nakamura, A. Anitha, K. Yamada, K. Hayashi, T. Asaka, H. X. Liu, D. Jin, K. Koizumi, M. S. Islam, J. J. Huang, W. J. Ma, U. H. Kim, S. J. Kim, K. Park, D. Kim, M. Kikuchi, Y. Ono, H. Nakatani, S. Suda, T. Miyachi, H. Hirai, A. Salmina, Y. A. Pichugina, A. A. Soumarokov N. Takei, N. Mori, M. Tsujii, T. Sugiyama, K. Yagi, M. Yamagishi, T. Sasaki, H. Yamasue, N. Kato, R. Hashimoto, M. Taniike, Y. Hayashi, J. Hamada, S. Suzuki, A. Ooi, M. Noda, Y. Kamiyama, M. A. Kido, O. Lopatina, M. Hashii, S. Amina, F. Malavasi, E. J. Huang, J. Zhang, N. Shimizu, T. Yoshikawa, A. Matsushima, Y. Minabe, H. Higashida, Two genetic variants of CD38 in subjects with autism spectrum disorder and controls. Neurosci. Res. 67, 181-191 (2010).
18. A. K. Wermter, I. Kamp-Becker, P. Hesse, G. Schulte-Körne, K. Strauch, H. Remschmidt, Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B, 629-639 (2010).
19. D. H. Skuse, A. Lori, J. F. Cubells, I. Lee, K. N. Conneely, K. Puura, T. Lehtimäki, E. B. Binder, L. J. Young, Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills. Proc. Natl. Acad. Sci. U.S.A. 111, 1987-1992 (2014).
20. D. LoParo, I. D. Waldman, The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: A meta-analysis. Mol. Psychiatry 10.1038/mp.2014.77 (2014).
21. M. J. Brownstein, J. T. Russell, H. Gainer, Synthesis, transport, and release of posterior pituitary hormones. Science 207, 373-378 (1980).
22. A. Kiss, J. D. Mikkelsen, Oxytocin-Anatomy and functional assignments: A minireview. Endocr. Regul. 39, 97-105 (2005).
23. H. S. Knobloch, A. Charlet, L. C. Hoffmann,M. Eliava, S. Khrulev, A. H. Cetin, P.Osten, M. K. Schwarz, P. H. Seeburg, R. Stoop, V. Grinevich, Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73, 553-566 (2012).
24. R. Stoop, Neuromodulation by oxytocin and vasopressin. Neuron 76, 142-159 (2012).
25. H. J. Lee, A. H. Macbeth, J. H. Pagani, W. S. Young III, Oxytocin: The great facilitator of life. Prog. Neurobiol. 88, 127-151 (2009).
26. J. L. Silverman, M. Yang, C. Lord, J. N. Crawley, Behavioural phenotyping assays for mouse models of autism. Nat. Rev. Neurosci. 11, 490-502 (2010).
27. J. L. Silverman,D. G. Smith, S. J. Rizzo, M. N. Karras, S. M. Turner, S. S. Tolu, D. K. Bryce, D. L. Smith, K. Fonseca, R. H. Ring, J. N. Crawley, Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci. Transl. Med. 4, 131ra51 (2012).
28. S. E. Smith, Y. D. Zhou, G. Zhang, Z. Jin, D. C. Stoppel, M. P. Anderson, Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice. Sci. Transl. Med. 3, 103ra97 (2011).
29. C. D. Chapman, W. H. Frey II, S. Craft, L. Danielyan, M. Hallschmid, H. B. Schiöth, C. Benedict, Intranasal treatment of central nervous system dysfunction in humans. Pharm. Res. 30, 2475-2484 (2013).
30. M. Ludwig, G. Leng, Dendritic peptide release and peptide-dependent behaviours. Nat. Rev. Neurosci. 7, 126-136 (2006).
31. I. D. Neumann, R. Maloumby, D. I. Beiderbeck, M. Lukas, R. Landgraf, Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice. Psychoneuroendocrinology 38, 1985-1993 (2013).
32. E. A. Simpson, V. Sclafani, A. Paukner, A. F. Hamel, M. A. Novak, J. S. Meyer, S. J. Suomi, P. F. Ferrari, Inhaled oxytocin increases positive social behaviors in newborn macaques. Proc. Natl. Acad. Sci. U.S.A. 111, 6922-6927 (2014).
33. N. Striepens, K. M. Kendrick, W. Maier, R. Hurlemann, Prosocial effects of oxytocin and clinical evidence for its therapeutic potential. Front. Neuroendocrinol. 32, 426-450 (2011).
34. J. E. Siljee, U. A. Unmehopa, A. Kalsbeek, D. F. Swaab, E. Fliers, A. Alkemade, Melanocortin 4 receptor distribution in the human hypothalamus. Eur. J. Endocrinol. 168, 361-369 (2013).
35. B. M. Kublaoui, T. Gemelli, K. P. Tolson, Y. Wang, A. R. Zinn, Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice. Mol. Endocrinol. 22, 1723-1734 (2008).
36. N. Sabatier, α-Melanocyte-stimulating hormone and oxytocin: A peptide signalling cascade in the hypothalamus. J. Neuroendocrinol. 18, 703-710 (2006).
37. M. E. Modi, L. J. Young, The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies. Horm. Behav. 61, 340-350 (2012).
38. S. C. Benoit, M. W. Schwartz, J. L. Lachey, M. M. Hagan, P. A. Rushing, K. A. Blake, K. A. Yagaloff, G. Kurylko, L. Franco, W. Danhoo, R. J. Seeley, A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J. Neurosci. 20, 3442-3448 (2000).
39. + channels in myelinated axons depends on Caspr2 and TAG-1. J. Cell Biol. 162, 1149-1160 (2003).
40. E. F. Lipari, D. Lipari, A. Gerbino, D. Di Liberto, M. Bellafiore, M. Catalano, B. Valentino, The hypothalamic magnocellular neurosecretory system in developing rats. Eur. J. Histochem. 45, 163-168 (2001).
41. Y. Yamamoto, B. S. Cushing, K. M. Kramer, P. D. Epperson, G. E. Hoffman, C. S. Carter, Neonatal manipulations of oxytocin alter expression of oxytocin and vasopressin immunoreactive cells in the paraventricular nucleus of the hypothalamus in a gender-specific manner. Neuroscience 125, 947-955 (2004).
42. J. J. Zheng, S. J. Li, X. D. Zhang, W. Y. Miao, D. Zhang, H. Yao, X. Yu, Oxytocin mediates early experience-dependent cross-modal plasticity in the sensory cortices. Nat. Neurosci. 17, 391-399 (2014).
43. T. H. Ahern, L. J. Young, The impact of early life family structure on adult social attachment, alloparental behavior, and the neuropeptide systems regulating affiliative behaviors in the monogamous prairie vole (Microtus ochrogaster). Front. Behav. Neurosci. 3, 17 (2009).
44. K. L. Bales, C. S. Carter, Developmental exposure to oxytocin facilitates partner preferences in male prairie voles (Microtus ochrogaster). Behav. Neurosci. 117, 854-859 (2003).
45. H. E. Ross, C. D. Cole, Y. Smith, I. D. Neumann, R. Landgraf, A. Z. Murphy, L. J. Young, Characterization of the oxytocin system regulating affiliative behavior in female prairie voles. Neuroscience 162, 892-903 (2009).
46. H. M. Lee, P. M. Giguere, B. L. Roth, DREADDs: Novel tools for drug discovery and development. Drug Discov. Today 19, 469-473 (2014).
47. C. McCall, T. Singer, The animal and human neuroendocrinology of social cognition, motivation and behavior. Nat. Neurosci. 15, 681-688 (2012).
48. G. Dölen, A. Darvishzadeh, K. W. Huang, R. C. Malenka, Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501, 179-184 (2013).
49. B. L. Teng, R. J. Nonneman, K. L. Agster, V. D. Nikolova, T. T. Davis, N. V. Riddick, L. K. Baker, C. A. Pedersen, M. B. Jarstfer, S. S. Moy, Prosocial effects of oxytocin in two mouse models of autism spectrum disorders. Neuropharmacology 72, 187-196 (2013).
50. Y. Aoki, N. Yahata, T. Watanabe, Y. Takano, Y. Kawakubo, H. Kuwabara, N. Iwashiro, T. Natsubori, H. Inoue, M. Suga, H. Takao, H. Sasaki, W. Gonoi, A. Kunimatsu, K. Kasai, H. Yamasue, Oxytocin improves behavioural and neural deficits in inferring others' social emotions in autism. Brain 137, 3073-3086 (2014).
51. T. Watanabe, O. Abe, H. Kuwabara, N. Yahata, Y. Takano, N. Iwashiro, T. Natsubori, Y. Aoki, H. Takao, Y. Kawakubo, Y. Kamio, N. Kato, Y. Miyashita, K. Kasai, H. Yamasue, Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: A randomized trial. JAMA Psychiatry 71, 166-175 (2014).
52. D. M. Cochran, D. Fallon, M. Hill, J. A. Frazier, The role of oxytocin in psychiatric disorders: A review of biological and therapeutic research findings. Harv. Rev. Psychiatry 21, 219-247 (2013).
53. C. Modahl, L. Green, D. Fein, M. Morris, L. Waterhouse, C. Feinstein, H. Levin, Plasma oxytocin levels in autistic children. Biol. Psychiatry 43, 270-277 (1998).
54. E. Andari, J. R. Duhamel, T. Zalla, E. Herbrecht, M. Leboyer, A. Sirigu, Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc. Natl. Acad. Sci. U.S.A. 107, 4389-4394 (2010).
55. L. M. Jansen, C. C. Gispen-deWied, V. M. Wiegant, H. G. Westenberg, B. E. Lahuis, H. van Engeland, Autonomic and neuroendocrine responses to a psychosocial stressor in adults with autistic spectrum disorder. J. Autism Dev. Disord. 36, 891-899 (2006).
56. J. D. Jacobson, K. A. Ellerbeck, K. A. Kelly, K. K. Fleming, T. R. Jamison, C. W. Coffey, C. M. Smith, R. M. Reese, S. A. Sands, Evidence for alterations in stimulatory G proteins and oxytocin levels in children with autism. Psychoneuroendocrinology 40, 159-169 (2014).
57. L. Green, D. Fein, C. Modahl, C. Feinstein, L. Waterhouse, M. Morris, Oxytocin and autistic disorder: Alterations in peptide forms. Biol. Psychiatry 50, 609-613 (2001).
58. K. J. Parker, J. P. Garner, R. A. Libove, S. A. Hyde, K. B. Hornbeak, D. S. Carson, C. P. Liao, J. M. Phillips, J. F. Hallmayer, A. Y. Hardan, Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder. Proc. Natl. Acad. Sci. U.S.A. 111, 12258-12263 (2014).
59. E. A. Hammock, P. Levitt, Oxytocin receptor ligand binding in embryonic tissue and postnatal brain development of the C57BL/6J mouse. Front. Behav. Neurosci. 7, 195 (2013).
60. K. M. Kramer, C. Choe, C. S. Carter, B. S. Cushing, Developmental effects of oxytocin on neural activation and neuropeptide release in response to social stimuli. Horm. Behav. 49, 206-214 (2006).
61. C. E. Barrett, M. E. Modi, B. C. Zhang, H. Walum, K. Inoue, L. J. Young, Neonatal melanocortin receptor agonist treatment reduces play fighting and promotes adult attachment in prairie voles in a sex-dependent manner. Neuropharmacology 85, 357-366 (2014).
62. K. Mogi, R. Ooyama, M. Nagasawa, T. Kikusui, Effects of neonatal oxytocin manipulation on development of social behaviors in mice. Physiol. Behav. 133, 68-75 (2014).
63. A. S. Suraev, M. T. Bowen, S. O. Ali, C. Hicks, L. Ramos, I. S. McGregor, Adolescent exposure to oxytocin, but not the selective oxytocin receptor agonist TGOT, increases social behavior and plasma oxytocin in adulthood. Horm. Behav. 65, 488-496 (2014).
64. S. F. Owen, S. N. Tuncdemir, P. L. Bader, N. N. Tirko, G. Fishell, R. W. Tsien, Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons. Nature 500, 458-462 (2013).
65. V. S. Sohal, F. Zhang, O. Yizhar, K. Deisseroth, Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459, 698-702 (2009).
66. M. Sala, D. Braida, D. Lentini,M. Busnelli, E. Bulgheroni, V. Capurro, A. Finardi, A. Donzelli, L. Pattini, T. Rubino, D. Parolaro, K. Nishimori, M. Parenti, B. Chini, Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: A neurobehavioral model of autism. Biol. Psychiatry 69, 875-882 (2011).
67. R. Tyzio, R. Cossart, I. Khalilov, M. Minlebaev, C. A. Hübner, A. Represa, Y. Ben-Ari, R. Khazipov, Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Science 314, 1788-1792 (2006).
68. R. Tyzio, R. Nardou, D. C. Ferrari, T. Tsintsadze, A. Shahrokhi, S. Eftekhari, I. Khalilov, V. Tsintsadze, C. Brouchoud, G. Chazal, E. Lemonnier, N. Lozovaya, N. Burnashev, Y. Ben-Ari, Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring. Science 343, 675-679 (2014).
69. L. Selby, C. Zhang, Q. Q. Sun, Major defects in neocortical GABAergic inhibitory circuits in mice lacking the fragile X mental retardation protein. Neurosci. Lett. 412, 227-232 (2007).
70. S. M. Francis, A. Sagar, T. Levin-Decanini, W. Liu, C. S. Carter, S. Jacob, Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders. Brain Res. 1580, 199-218 (2014).
71. S. S. Hall, A. A. Lightbody, B. E. McCarthy, K. J. Parker, A. L. Reiss, Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome. Psychoneuroendocrinology 37, 509-518 (2012).
72. D. T. Theodosis, M. Schachner, I. D. Neumann, Oxytocin neuron activation in NCAM-deficient mice: Anatomical and functional consequences. Eur. J. Neurosci. 20, 3270-3280 (2004).
73. G. R. Anderson, T. Galfin, W. Xu, J. Aoto, R. C. Malenka, T. C. Südhof, Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development. Proc. Natl. Acad. Sci. U.S.A. 109, 18120-18125 (2012).
74. K. P. Tolson, T. Gemelli, L. Gautron, J. K. Elmquist, A. R. Zinn, B. M. Kublaoui, Postnatal Sim1 deficiency causes hyperphagic obesity and reduced Mc4r and oxytocin expression. J. Neurosci. 30, 3803-3812 (2010).
75. R. L. Fields, T. A. Ponzio, M. Kawasaki, H. Gainer, Cell-type specific oxytocin gene expression from AAV delivered promoter deletion constructs into the rat supraoptic nucleus in vivo. PLOS One 7, e32085 (2012).
76. A. Cetin, S. Komai, M. Eliava, P. H. Seeburg, P. Osten, Stereotaxic gene delivery in the rodent brain. Nat. Protoc. 1, 3166-3173 (2006).