4.4 Review

Implications of cellular models of dopamine neurons for disease

Journal

JOURNAL OF NEUROPHYSIOLOGY
Volume 116, Issue 6, Pages 2815-2830

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00530.2016

Keywords

nonlinear dynamics; dopaminergic signaling

Funding

  1. National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) [R01-NS-061097]
  2. Russian Academic Excellence Project [5-100]
  3. L'Agence Nationale de la Recherche NEUCOMP [ANR-10-LABX-0087 IEC, ANR-10-IDEX-0001-02 PSL]
  4. NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01-AA-022821]
  5. Eastern Washington University Faculty Grant for Research and Creative Works
  6. NIH NINDS Intramural Research Program [NS-003135]

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This review addresses the present state of single-cell models of the firing pattern of midbrain dopamine neurons and the insights that can be gained from these models into the underlying mechanisms for diseases such as Parkinson's, addiction, and schizophrenia. We will explain the analytical technique of separation of time scales and show how it can produce insights into mechanisms using simplified single-compartment models. We also use morphologically realistic multicompartmental models to address spatially heterogeneous aspects of neural signaling and neural metabolism. Separation of time scale analyses are applied to pacemaking, bursting, and depolarization block in dopamine neurons. Differences in subpopulations with respect to metabolic load are addressed using multicompartmental models.

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