Little is known about the development of abnormal repetitive behaviors (e.g., stereotypies, rituals) in children at risk for autism and related neurodevelopmental disorders. This lack of knowledge precludes effective early intervention and prevention strategies. Appropriate animal models could provide a wealth of information about the developmental characteristics of such behavior, particularly the neurobiological mechanisms mediating the transition to persistent, fixed, and habitual behavior. Thus, the overall goal of this project will be to examine the development of repetitive motor behavior in a mouse model and identify the neurobiological mechanisms mediating the emergence and expression of habitual, persistent and inflexible motor behavior. We will test hypotheses that the development of persistent repetitive behavior is associated with alterations in corti co-basal ganglia circuitry. Specifically, we will test hypotheses that alterations in basal ganglia pathways (direct and indirect) (Aim #2) as well as striatal compartments (striosome and matrix) (Aim #3) mediate the transition to persistent repetitive behavior. Pharmacological experiments in Aim #2 will not only aid in identifying neurobiological mechanisms but will also identify potential therapeutic targets for drug development.

Public Health Relevance

Little is known about the development of abnormal repetitive behaviors (e.g., stereotypies, rituals) in children at risk for autism and related neurodevelopmental disorders. This lack of knowledge precludes effective early intervention and prevention strategies. Appropriate animal models could provide a wealth of information about the developmental characteristics of such behavior, particularly the neurobiological mechanisms mediating the transition to the persistent, fixed, and habitual behaviors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH080055-01A2
Application #
7652493
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Vicentic, Aleksandra
Project Start
2009-05-15
Project End
2011-04-30
Budget Start
2009-05-15
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$362,971
Indirect Cost
Name
University of Florida
Department
Psychiatry
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Wilkes, B J; Lewis, M H (2018) The neural circuitry of restricted repetitive behavior: Magnetic resonance imaging in neurodevelopmental disorders and animal models. Neurosci Biobehav Rev 92:152-171
Whitehouse, Cristina M; Curry-Pochy, Lisa S; Shafer, Robin et al. (2017) Reversal learning in C58 mice: Modeling higher order repetitive behavior. Behav Brain Res 332:372-378
Bechard, Allison R; Bliznyuk, Nikolay; Lewis, Mark H (2017) The development of repetitive motor behaviors in deer mice: Effects of environmental enrichment, repeated testing, and differential mediation by indirect basal ganglia pathway activation. Dev Psychobiol 59:390-399
Bechard, Allison R; Lewis, Mark H (2016) Transgenerational effects of environmental enrichment on repetitive motor behavior development. Behav Brain Res 307:145-9
Bechard, Allison R; Cacodcar, Nadia; King, Michael A et al. (2016) How does environmental enrichment reduce repetitive motor behaviors? Neuronal activation and dendritic morphology in the indirect basal ganglia pathway of a mouse model. Behav Brain Res 299:122-31
Whitehouse, Cristina M; Lewis, Mark H (2015) Repetitive Behavior in Neurodevelopmental Disorders: Clinical and Translational Findings. Behav Anal 38:163-178
Muehlmann, Amber M; Bliznyuk, Nikolay; Duerr, Isaac et al. (2015) Repetitive motor behavior: further characterization of development and temporal dynamics. Dev Psychobiol 57:201-11
Muehlmann, A M; Kies, S D; Turner, C A et al. (2012) Self-injurious behaviour: limbic dysregulation and stress effects in an animal model. J Intellect Disabil Res 56:490-500
Tanimura, Yoko; King, Michael A; Williams, Dustin K et al. (2011) Development of repetitive behavior in a mouse model: roles of indirect and striosomal basal ganglia pathways. Int J Dev Neurosci 29:461-7
Tanimura, Yoko; Yang, Mark C K; Ottens, Andrew K et al. (2010) Development and temporal organization of repetitive behavior in an animal model. Dev Psychobiol 52:813-24

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