Identification of the embryonic stage when injury can cause autism has led to the insight that the disorder is initiated by changes in the developing brain stem. The shortening of the hindbrain and loss of cranial nerve neurons in an animal model of the insult and a human cause of autism resemble features of the Hoxa-1 transgenic knockout mice. Thus, it is now possible to suggest a unifying hypothesis regarding the multiple etiologies of autism; We propose that teratogens and genetic defects lead to similar developmental changes in the brain stem because mutations of early developmental genes are the cause of familial cases and the teratogens which cause the disease act by interfering with the function of the same genes. The new finding that one of the candidate genes is abnormal in some cases of autism supports this hypothesis. In Project I. we shall create an animal model based on mutation of early developmental genes. We have already developed an animal model based on mutation of early developmental genes. We have already developed an animal model of teratologically-induced brain stem injury using valproic acid. Our plan to evaluate the behavior of animal models await the identification of tasks which a) discriminate autism from other developmental disabilities b) are applicable to animals c) are restricted in the functions required so that they might be connected to specific brain regions or systems. We have identified two tasks with the potential to meet these criteria- the conditioned eye-blink response in teratologic and genetic animal models of autism, and then apply the same task to human cases of autism and other developmental disabilities. A long-term goal is to develop an animal analogue of the attention task which will be applied to teratologic and genetic animal models of autism. The overall goal of this project is to provide tests of behavioral parallelism not only in our own animal models of autism, but in those developed by others.

Project Start
2002-06-01
Project End
2003-05-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
2002
Total Cost
$165,355
Indirect Cost
Name
University of Rochester
Department
Type
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Jablonski, Sarah A; Watson, Deborah J; Stanton, Mark E (2010) Role of medial prefrontal NMDA receptors in spatial delayed alternation in 19-, 26-, and 33-day-old rats. Dev Psychobiol 52:583-91
Murawski, Nathen J; Brown, Kevin L; Stanton, Mark E (2009) Interstimulus interval (ISI) discrimination of the conditioned eyeblink response in a rodent model of autism. Behav Brain Res 196:297-303
Watson, Deborah J; Herbert, Mariel R; Stanton, Mark E (2009) NMDA receptor involvement in spatial delayed alternation in developing rats. Behav Neurosci 123:44-53
Watson, Deborah J; Stanton, Mark E (2009) Spatial discrimination reversal learning in weanling rats is impaired by striatal administration of an NMDA-receptor antagonist. Learn Mem 16:564-72
Burman, M A; Murawski, N J; Schiffino, F L et al. (2009) Factors governing single-trial contextual fear conditioning in the weanling rat. Behav Neurosci 123:1148-52
Watson, Deborah J; Stanton, Mark E (2009) Medial prefrontal administration of MK-801 impairs T-maze discrimination reversal learning in weanling rats. Behav Brain Res 205:57-66
Watson, Deborah J; Stanton, Mark E (2009) Intrahippocampal administration of an NMDA-receptor antagonist impairs spatial discrimination reversal learning in weanling rats. Neurobiol Learn Mem 92:89-98
Levy, Susan E; Hyman, Susan L (2008) Complementary and alternative medicine treatments for children with autism spectrum disorders. Child Adolesc Psychiatr Clin N Am 17:803-20, ix
Stanton, Mark E; Peloso, Elizabeth; Brown, Kevin L et al. (2007) Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism. Behav Brain Res 176:133-40
Stodgell, Christopher J; Ingram, Jennifer L; O'Bara, Melanie et al. (2006) Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action. Neurotoxicol Teratol 28:617-24

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