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Autism and Dopamine

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The Molecular Basis of Autism

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

Abstract

In this chapter we present data from two mutant mouse strains (lurcher and Fmr1) that share in common with patients diagnosed with an autism spectrum disorder, the characteristic of developmental cerebellar neuropathology involving Purkinje cells. Evidence is presented indicating that Purkinje cell number has a profound influence on behaviors that are commonly disrupted in autism spectrum disorders including hyperactivity, increased repetitive behavior, and deficits in executive function. Additional experiments are presented which indicate that these behavioral deficits stem from developmental loss of cerebellar output that occurs as a function of Purkinje cell loss. Loss or dysregulation of Purkinje cell output to the deep cerebellar nuclei such as the cerebellar dentate nucleus in turn results in alterations in the functionality of cerebellar projections via the thalamus and ventral tegmental area to the medial prefrontal cortex (mPFC). This loss of functionality prominently includes reductions in cerebellar-mediated mPFC dopamine release. The reduction in mPFC dopamine release is likely caused by coincident reductions in glutamate available for release from cerebellar projections to the thalamus and ventral tegmental area (VTA). This loss of functionality also includes a shift in the balance of influence of the cerebellum on the mPFC, away from the cerebellar circuitry projecting to the ventral tegmental area, towards cerebellar projections to the thalamus. All of these changes consistently occurred in both lurcher and Fmr1 mutant mice. In addition to modulating mPFC dopamine, the possibility that the cerebellum may also influence dopamine dynamics in the caudate and nucleus accumbens is also considered.

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Acknowledgments

This work was supported by a grant from the National Institute of Neurological Disorders and Stroke (R01 NS063009).

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Authors and Affiliations

  1. Department of Psychology, University of Memphis, 400 Innovation Drive, 38152, Memphis, TN, USA

    Guy Mittleman PhD

  2. Department of Psychological Science, Ball State University, North Quad, room 104, 47306, Muncie, IN, USA

    Charles D. Blaha PhD

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  1. Guy Mittleman PhD
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  2. Charles D. Blaha PhD
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Correspondence to Guy Mittleman PhD .

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  1. Neuroscience and Pharmacology MMC 392, University of Minnesota Medical School, Minneapolis, Minnesota, USA

    S. Hossein Fatemi

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Mittleman, G., Blaha, C. (2015). Autism and Dopamine. In: Fatemi, S. (eds) The Molecular Basis of Autism. Contemporary Clinical Neuroscience. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2190-4_11

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